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Surgery_Schwartz_3802
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Surgery_Schwartz
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in BRCA2 families is an autosomal dominant trait and has a high penetrance. Approximately 50% of children of carriers inherit the trait. Unlike male carriers of BRCA1 mutations, men with germline mutations in BRCA2 have an estimated breast cancer risk of 6%, which represents a 100-fold increase over the risk in the general male population. BRCA2-associated breast cancers are invasive ductal carcinomas, which are more likely to be well differentiated and to express hormone receptors than are BRCA1-associated breast cancers. BRCA2-associated breast cancer has a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases, a higher prevalence of bilateral breast cancer, and the presence of associ-ated cancers in some affected individuals, specifically ovarian, colon, prostate, pancreatic, gallbladder, bile duct, and stomach cancers, as well as melanoma. A number of founder mutations have been identified in BRCA2. The 6174delT mutation is found
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Surgery_Schwartz. in BRCA2 families is an autosomal dominant trait and has a high penetrance. Approximately 50% of children of carriers inherit the trait. Unlike male carriers of BRCA1 mutations, men with germline mutations in BRCA2 have an estimated breast cancer risk of 6%, which represents a 100-fold increase over the risk in the general male population. BRCA2-associated breast cancers are invasive ductal carcinomas, which are more likely to be well differentiated and to express hormone receptors than are BRCA1-associated breast cancers. BRCA2-associated breast cancer has a number of distinguishing clinical features, such as an early age of onset compared with sporadic cases, a higher prevalence of bilateral breast cancer, and the presence of associ-ated cancers in some affected individuals, specifically ovarian, colon, prostate, pancreatic, gallbladder, bile duct, and stomach cancers, as well as melanoma. A number of founder mutations have been identified in BRCA2. The 6174delT mutation is found
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Surgery_Schwartz_3803
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Surgery_Schwartz
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ovarian, colon, prostate, pancreatic, gallbladder, bile duct, and stomach cancers, as well as melanoma. A number of founder mutations have been identified in BRCA2. The 6174delT mutation is found in Ashkenazi Jews with a prevalence of 1.2% and accounts for 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.106 Another BRCA2 founder mutation, 999del5, is observed in Icelandic and Finnish popula-tions, while more recently 3036delACAA has been observed in a number of Spanish families.107-109Identification of BRCA Mutation Carriers. Identifying hereditary risk for breast cancer is a four-step process that includes: (a) obtaining a complete, multigenerational family history, (b) assessing the appropriateness of genetic testing for a particular patient, (c) counseling the patient, and (d) interpret-ing the results of testing.110 Genetic testing should not be offered in isolation, but only in conjunction with patient education and counseling, including
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Surgery_Schwartz. ovarian, colon, prostate, pancreatic, gallbladder, bile duct, and stomach cancers, as well as melanoma. A number of founder mutations have been identified in BRCA2. The 6174delT mutation is found in Ashkenazi Jews with a prevalence of 1.2% and accounts for 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women.106 Another BRCA2 founder mutation, 999del5, is observed in Icelandic and Finnish popula-tions, while more recently 3036delACAA has been observed in a number of Spanish families.107-109Identification of BRCA Mutation Carriers. Identifying hereditary risk for breast cancer is a four-step process that includes: (a) obtaining a complete, multigenerational family history, (b) assessing the appropriateness of genetic testing for a particular patient, (c) counseling the patient, and (d) interpret-ing the results of testing.110 Genetic testing should not be offered in isolation, but only in conjunction with patient education and counseling, including
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Surgery_Schwartz_3804
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Surgery_Schwartz
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counseling the patient, and (d) interpret-ing the results of testing.110 Genetic testing should not be offered in isolation, but only in conjunction with patient education and counseling, including referral to a genetic counselor. Initial determinations include whether the individual is an appropriate candidate for genetic testing and whether genetic testing will be informative for personal and clinical decision-making. A thor-ough and accurate family history is essential to this process, and the maternal and paternal sides of the family are both assessed because 50% of the women with a BRCA mutation have inher-ited the mutation from their fathers. To help clinicians advise women about genetic testing, statistically based models that determine the probability that an individual carries a BRCA mutation have been developed. A method for calculating carrier probability that has been demonstrated to have acceptable per-formance (i.e., both in terms of calibration and discrimination) such
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Surgery_Schwartz. counseling the patient, and (d) interpret-ing the results of testing.110 Genetic testing should not be offered in isolation, but only in conjunction with patient education and counseling, including referral to a genetic counselor. Initial determinations include whether the individual is an appropriate candidate for genetic testing and whether genetic testing will be informative for personal and clinical decision-making. A thor-ough and accurate family history is essential to this process, and the maternal and paternal sides of the family are both assessed because 50% of the women with a BRCA mutation have inher-ited the mutation from their fathers. To help clinicians advise women about genetic testing, statistically based models that determine the probability that an individual carries a BRCA mutation have been developed. A method for calculating carrier probability that has been demonstrated to have acceptable per-formance (i.e., both in terms of calibration and discrimination) such
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Surgery_Schwartz_3805
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Surgery_Schwartz
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BRCA mutation have been developed. A method for calculating carrier probability that has been demonstrated to have acceptable per-formance (i.e., both in terms of calibration and discrimination) such as the Manchester scoring system and BODICEA should be used to offer referral to a specialist genetic clinic. A heredi-tary risk of breast cancer is considered if a family includes Ash-kenazi Jewish heritage; a first-degree relative with breast cancer before age 50; a history of ovarian cancer at any age in the patient or firstor second-degree relative with ovarian cancer; breast and ovarian cancer in the same individual; two or more firstor second-degree relatives with breast cancer at any age; patient or relative with bilateral breast cancer; and male breast cancer in a relative at any age.111 The threshold for genetic test-ing is lower in individuals who are members of ethnic groups in whom the mutation prevalence is increased.BRCA Mutation Testing. Appropriate counseling for the
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Surgery_Schwartz. BRCA mutation have been developed. A method for calculating carrier probability that has been demonstrated to have acceptable per-formance (i.e., both in terms of calibration and discrimination) such as the Manchester scoring system and BODICEA should be used to offer referral to a specialist genetic clinic. A heredi-tary risk of breast cancer is considered if a family includes Ash-kenazi Jewish heritage; a first-degree relative with breast cancer before age 50; a history of ovarian cancer at any age in the patient or firstor second-degree relative with ovarian cancer; breast and ovarian cancer in the same individual; two or more firstor second-degree relatives with breast cancer at any age; patient or relative with bilateral breast cancer; and male breast cancer in a relative at any age.111 The threshold for genetic test-ing is lower in individuals who are members of ethnic groups in whom the mutation prevalence is increased.BRCA Mutation Testing. Appropriate counseling for the
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Surgery_Schwartz_3806
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Surgery_Schwartz
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age.111 The threshold for genetic test-ing is lower in individuals who are members of ethnic groups in whom the mutation prevalence is increased.BRCA Mutation Testing. Appropriate counseling for the individual being tested for a BRCA mutation is strongly rec-ommended, and documentation of informed consent is required.110,112 The test that is clinically available for analyzing BRCA mutations is gene sequence analysis. In a family with a history suggestive of hereditary breast cancer and no previously Brunicardi_Ch17_p0541-p0612.indd 55901/03/19 5:04 PM 560SPECIFIC CONSIDERATIONSPART IItested member, the most informative strategy is first to test an affected family member. This person undergoes complete sequence analysis of both the BRCA1 and BRCA2 genes. If a mutation is identified, relatives are usually tested only for that specific mutation. An individual of Ashkenazi Jewish ancestry is tested initially for the three specific mutations that account for hereditary breast and
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Surgery_Schwartz. age.111 The threshold for genetic test-ing is lower in individuals who are members of ethnic groups in whom the mutation prevalence is increased.BRCA Mutation Testing. Appropriate counseling for the individual being tested for a BRCA mutation is strongly rec-ommended, and documentation of informed consent is required.110,112 The test that is clinically available for analyzing BRCA mutations is gene sequence analysis. In a family with a history suggestive of hereditary breast cancer and no previously Brunicardi_Ch17_p0541-p0612.indd 55901/03/19 5:04 PM 560SPECIFIC CONSIDERATIONSPART IItested member, the most informative strategy is first to test an affected family member. This person undergoes complete sequence analysis of both the BRCA1 and BRCA2 genes. If a mutation is identified, relatives are usually tested only for that specific mutation. An individual of Ashkenazi Jewish ancestry is tested initially for the three specific mutations that account for hereditary breast and
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Surgery_Schwartz_3807
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Surgery_Schwartz
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relatives are usually tested only for that specific mutation. An individual of Ashkenazi Jewish ancestry is tested initially for the three specific mutations that account for hereditary breast and ovarian cancer in that population. If results of that test are negative, it may then be appropriate to fully analyze the BRCA1 and BRCA2 genes.A positive test result is one that discloses the presence of a BRCA mutation that interferes with translation or function of the BRCA protein. A woman who carries a deleterious mutation has a breast cancer risk of up to 85% (in some families) as well as a greatly increased risk of ovarian cancer. A negative test result is interpreted according to the individual’s personal and family history, especially whether a mutation has been previously iden-tified in the family, in which case the woman is generally tested only for that specific mutation. If the mutation is not present, the woman’s risk of breast or ovarian cancer may be no greater than that of
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Surgery_Schwartz. relatives are usually tested only for that specific mutation. An individual of Ashkenazi Jewish ancestry is tested initially for the three specific mutations that account for hereditary breast and ovarian cancer in that population. If results of that test are negative, it may then be appropriate to fully analyze the BRCA1 and BRCA2 genes.A positive test result is one that discloses the presence of a BRCA mutation that interferes with translation or function of the BRCA protein. A woman who carries a deleterious mutation has a breast cancer risk of up to 85% (in some families) as well as a greatly increased risk of ovarian cancer. A negative test result is interpreted according to the individual’s personal and family history, especially whether a mutation has been previously iden-tified in the family, in which case the woman is generally tested only for that specific mutation. If the mutation is not present, the woman’s risk of breast or ovarian cancer may be no greater than that of
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Surgery_Schwartz_3808
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Surgery_Schwartz
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in the family, in which case the woman is generally tested only for that specific mutation. If the mutation is not present, the woman’s risk of breast or ovarian cancer may be no greater than that of the general population. In addition, no BRCA muta-tion can be passed on to the woman’s children. In the absence of a previously identified mutation, a negative test result in an affected individual generally indicates that a BRCA mutation is not responsible for the familial cancer. However, the possibil-ity remains of an unusual abnormality in one of these genes that cannot yet be identified through clinical testing. It also is possible that the familial cancer is indeed caused by an identifi-able BRCA mutation but that the individual tested had sporadic cancer, a situation known as phenocopy. This is especially pos-sible if the individual tested developed breast cancer close to the age of onset of the general population (age 60 years or older) rather than before age 50 years, as is
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Surgery_Schwartz. in the family, in which case the woman is generally tested only for that specific mutation. If the mutation is not present, the woman’s risk of breast or ovarian cancer may be no greater than that of the general population. In addition, no BRCA muta-tion can be passed on to the woman’s children. In the absence of a previously identified mutation, a negative test result in an affected individual generally indicates that a BRCA mutation is not responsible for the familial cancer. However, the possibil-ity remains of an unusual abnormality in one of these genes that cannot yet be identified through clinical testing. It also is possible that the familial cancer is indeed caused by an identifi-able BRCA mutation but that the individual tested had sporadic cancer, a situation known as phenocopy. This is especially pos-sible if the individual tested developed breast cancer close to the age of onset of the general population (age 60 years or older) rather than before age 50 years, as is
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Surgery_Schwartz_3809
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Surgery_Schwartz
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This is especially pos-sible if the individual tested developed breast cancer close to the age of onset of the general population (age 60 years or older) rather than before age 50 years, as is characteristic of BRCA mutation carriers. Overall, the false-negative rate for BRCA mutation testing is <5%. Some test results, especially when a single base-pair change (missense mutation) is identified, may be difficult to interpret. This is because single base-pair changes do not always result in a nonfunctional protein. Thus, missense mutations not located within critical functional domains, or those that cause only minimal changes in protein structure, may not be disease associated and are usually reported as indetermi-nate results. In communicating indeterminate results to women, care must be taken to relay the uncertain cancer risk associ-ated with this type of mutation and to emphasize that ongoing research might clarify its meaning. In addition, testing other family members with breast
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Surgery_Schwartz. This is especially pos-sible if the individual tested developed breast cancer close to the age of onset of the general population (age 60 years or older) rather than before age 50 years, as is characteristic of BRCA mutation carriers. Overall, the false-negative rate for BRCA mutation testing is <5%. Some test results, especially when a single base-pair change (missense mutation) is identified, may be difficult to interpret. This is because single base-pair changes do not always result in a nonfunctional protein. Thus, missense mutations not located within critical functional domains, or those that cause only minimal changes in protein structure, may not be disease associated and are usually reported as indetermi-nate results. In communicating indeterminate results to women, care must be taken to relay the uncertain cancer risk associ-ated with this type of mutation and to emphasize that ongoing research might clarify its meaning. In addition, testing other family members with breast
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Surgery_Schwartz_3810
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Surgery_Schwartz
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taken to relay the uncertain cancer risk associ-ated with this type of mutation and to emphasize that ongoing research might clarify its meaning. In addition, testing other family members with breast cancer to determine if a genetic variant tracks with their breast cancer may provide clarification as to its significance. Indeterminate genetic variance currently accounts for 12% of the test results.Concern has been expressed that the identification of hereditary risk for breast cancer may interfere with access to affordable health insurance. This concern refers to discrimina-tion directed against an individual or family based solely on an apparent or perceived genetic variation from the normal human genotype. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) made it illegal in the United States for group health plans to consider genetic information as a preexist-ing condition or to use it to deny or limit coverage. Most states also have passed laws that prevent
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Surgery_Schwartz. taken to relay the uncertain cancer risk associ-ated with this type of mutation and to emphasize that ongoing research might clarify its meaning. In addition, testing other family members with breast cancer to determine if a genetic variant tracks with their breast cancer may provide clarification as to its significance. Indeterminate genetic variance currently accounts for 12% of the test results.Concern has been expressed that the identification of hereditary risk for breast cancer may interfere with access to affordable health insurance. This concern refers to discrimina-tion directed against an individual or family based solely on an apparent or perceived genetic variation from the normal human genotype. The Health Insurance Portability and Accountability Act of 1996 (HIPAA) made it illegal in the United States for group health plans to consider genetic information as a preexist-ing condition or to use it to deny or limit coverage. Most states also have passed laws that prevent
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Surgery_Schwartz_3811
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Surgery_Schwartz
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illegal in the United States for group health plans to consider genetic information as a preexist-ing condition or to use it to deny or limit coverage. Most states also have passed laws that prevent genetic discrimination in the provision of health insurance. In addition, individuals applying for health insurance are not required to report whether relatives have undergone genetic testing for cancer risk, only whether those relatives have actually been diagnosed with cancer. Currently, there is little documented evidence of genetic dis-crimination resulting from findings of available genetic tests.Cancer Prevention for BRCA Mutation Carriers. Risk man-agement strategies for BRCA1 and BRCA2 mutation carriers include the following:1. Risk-reducing mastectomy and reconstruction2. Risk-reducing salpingo-oophorectomy3. Intensive surveillance for breast and ovarian cancer4. ChemopreventionAlthough removal of breast tissue reduces the likeli-hood that BRCA1 and BRCA2 mutation carriers will
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Surgery_Schwartz. illegal in the United States for group health plans to consider genetic information as a preexist-ing condition or to use it to deny or limit coverage. Most states also have passed laws that prevent genetic discrimination in the provision of health insurance. In addition, individuals applying for health insurance are not required to report whether relatives have undergone genetic testing for cancer risk, only whether those relatives have actually been diagnosed with cancer. Currently, there is little documented evidence of genetic dis-crimination resulting from findings of available genetic tests.Cancer Prevention for BRCA Mutation Carriers. Risk man-agement strategies for BRCA1 and BRCA2 mutation carriers include the following:1. Risk-reducing mastectomy and reconstruction2. Risk-reducing salpingo-oophorectomy3. Intensive surveillance for breast and ovarian cancer4. ChemopreventionAlthough removal of breast tissue reduces the likeli-hood that BRCA1 and BRCA2 mutation carriers will
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Surgery_Schwartz_3812
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Surgery_Schwartz
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salpingo-oophorectomy3. Intensive surveillance for breast and ovarian cancer4. ChemopreventionAlthough removal of breast tissue reduces the likeli-hood that BRCA1 and BRCA2 mutation carriers will develop breast cancer, mastectomy does not remove all breast tissue, and women continue to be at risk because a germline muta-tion is present in any remaining breast tissue. For postmeno-pausal BRCA1 and BRCA2 mutation carriers who have not had a mastectomy, it may be advisable to avoid hormone replace-ment therapy because no data exist regarding the effect of the therapy on the penetrance of breast cancer susceptibility genes. Because breast cancers in BRCA mutation carriers have the same mammographic appearance as breast cancers in noncarri-ers, a screening mammogram is likely to be effective in BRCA mutation carriers, provided it is performed and interpreted by an experienced radiologist with a high level of suspicion. Pres-ent screening recommendations for BRCA mutation carriers who do
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Surgery_Schwartz. salpingo-oophorectomy3. Intensive surveillance for breast and ovarian cancer4. ChemopreventionAlthough removal of breast tissue reduces the likeli-hood that BRCA1 and BRCA2 mutation carriers will develop breast cancer, mastectomy does not remove all breast tissue, and women continue to be at risk because a germline muta-tion is present in any remaining breast tissue. For postmeno-pausal BRCA1 and BRCA2 mutation carriers who have not had a mastectomy, it may be advisable to avoid hormone replace-ment therapy because no data exist regarding the effect of the therapy on the penetrance of breast cancer susceptibility genes. Because breast cancers in BRCA mutation carriers have the same mammographic appearance as breast cancers in noncarri-ers, a screening mammogram is likely to be effective in BRCA mutation carriers, provided it is performed and interpreted by an experienced radiologist with a high level of suspicion. Pres-ent screening recommendations for BRCA mutation carriers who do
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Surgery_Schwartz_3813
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Surgery_Schwartz
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in BRCA mutation carriers, provided it is performed and interpreted by an experienced radiologist with a high level of suspicion. Pres-ent screening recommendations for BRCA mutation carriers who do not undergo risk-reducing mastectomy include clinical breast examination every 6 months and mammography every 12 months beginning at age 25 years because the risk of breast cancer in BRCA mutation carriers increases after age 30 years. Recent attention has been focused on the use of MRI for breast cancer screening in high-risk individuals and known BRCA mutation carriers. MRI appears to be more sensitive at detect-ing breast cancer in younger women with dense breasts.113 How-ever, as noted previously, MRI does lead to the detection of benign breast lesions that cannot easily be distinguished from malignancy, and these false-positive events can result in more interventions, including biopsy specimens. The current recom-mendations from the American Cancer Society are for annual MRI in women
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Surgery_Schwartz. in BRCA mutation carriers, provided it is performed and interpreted by an experienced radiologist with a high level of suspicion. Pres-ent screening recommendations for BRCA mutation carriers who do not undergo risk-reducing mastectomy include clinical breast examination every 6 months and mammography every 12 months beginning at age 25 years because the risk of breast cancer in BRCA mutation carriers increases after age 30 years. Recent attention has been focused on the use of MRI for breast cancer screening in high-risk individuals and known BRCA mutation carriers. MRI appears to be more sensitive at detect-ing breast cancer in younger women with dense breasts.113 How-ever, as noted previously, MRI does lead to the detection of benign breast lesions that cannot easily be distinguished from malignancy, and these false-positive events can result in more interventions, including biopsy specimens. The current recom-mendations from the American Cancer Society are for annual MRI in women
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Surgery_Schwartz_3814
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Surgery_Schwartz
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malignancy, and these false-positive events can result in more interventions, including biopsy specimens. The current recom-mendations from the American Cancer Society are for annual MRI in women with a 20% to 25% or greater lifetime risk of developing breast cancer (mainly based on family history), women with a known BRCA1 or BRCA2 mutation, those who have a first-degree relative with a BRCA1 or BRCA2 mutation and have not had genetic testing themselves, women who were treated with radiation therapy to the chest between the ages of 10 and 30 years, and those who have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or a first-degree relative with one of these syndromes.75,114 Despite a 49% reduction in the overall incidence of breast cancer and a 69% reduction in the incidence of estrogen receptor positive tumors in high-risk women taking tamoxifen reported in the NSABP P1 trial, there is insufficient evidence to recommend the use of tamoxifen uniformly
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Surgery_Schwartz. malignancy, and these false-positive events can result in more interventions, including biopsy specimens. The current recom-mendations from the American Cancer Society are for annual MRI in women with a 20% to 25% or greater lifetime risk of developing breast cancer (mainly based on family history), women with a known BRCA1 or BRCA2 mutation, those who have a first-degree relative with a BRCA1 or BRCA2 mutation and have not had genetic testing themselves, women who were treated with radiation therapy to the chest between the ages of 10 and 30 years, and those who have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or a first-degree relative with one of these syndromes.75,114 Despite a 49% reduction in the overall incidence of breast cancer and a 69% reduction in the incidence of estrogen receptor positive tumors in high-risk women taking tamoxifen reported in the NSABP P1 trial, there is insufficient evidence to recommend the use of tamoxifen uniformly
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Surgery_Schwartz_3815
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Surgery_Schwartz
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in the incidence of estrogen receptor positive tumors in high-risk women taking tamoxifen reported in the NSABP P1 trial, there is insufficient evidence to recommend the use of tamoxifen uniformly for BRCA1 mutation carriers.60 Cancers arising in BRCA1 mutation carriers are usually high grade and are most often hormone receptor negative. Approxi-mately 66% of BRCA1-associated DCIS lesions are estrogen receptor negative, which suggests early acquisition of the hor-mone-independent phenotype. In the NSABP P1 trial there was a 62% reduction in the incidence of breast cancer in BRCA2 carriers, similar to the overall reduction seen in the P1 trial. In contrast, there was no reduction seen in breast cancer incidence in BRCA1 carriers who started tamoxifen in P1 age 35 years or Brunicardi_Ch17_p0541-p0612.indd 56001/03/19 5:04 PM 561THE BREASTCHAPTER 17older.115 Tamoxifen appears to be more effective at preventing estrogen receptor-positive breast cancers.The risk of ovarian cancer in
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Surgery_Schwartz. in the incidence of estrogen receptor positive tumors in high-risk women taking tamoxifen reported in the NSABP P1 trial, there is insufficient evidence to recommend the use of tamoxifen uniformly for BRCA1 mutation carriers.60 Cancers arising in BRCA1 mutation carriers are usually high grade and are most often hormone receptor negative. Approxi-mately 66% of BRCA1-associated DCIS lesions are estrogen receptor negative, which suggests early acquisition of the hor-mone-independent phenotype. In the NSABP P1 trial there was a 62% reduction in the incidence of breast cancer in BRCA2 carriers, similar to the overall reduction seen in the P1 trial. In contrast, there was no reduction seen in breast cancer incidence in BRCA1 carriers who started tamoxifen in P1 age 35 years or Brunicardi_Ch17_p0541-p0612.indd 56001/03/19 5:04 PM 561THE BREASTCHAPTER 17older.115 Tamoxifen appears to be more effective at preventing estrogen receptor-positive breast cancers.The risk of ovarian cancer in
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Surgery_Schwartz_3816
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Surgery_Schwartz
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56001/03/19 5:04 PM 561THE BREASTCHAPTER 17older.115 Tamoxifen appears to be more effective at preventing estrogen receptor-positive breast cancers.The risk of ovarian cancer in BRCA1 and BRCA2 muta-tion carriers ranges from 20% to 40%, which is 10 times higher than that in the general population. Risk-reducing salpingo-oophorectomy is a reasonable prevention option in mutation carriers. In women with a documented BRCA1 or BRCA2 mutation, consideration for bilateral risk-reducing salpingo-oophorectomy should be between the ages of 35 and 40 years at the completion of childbearing. Removing the ovaries reduces the risk of ovarian cancer and breast cancer when per-formed in premenopausal BRCA mutation carriers. Hormone replacement therapy is discussed with the patient at the time of oophorectomy. The Cancer Genetics Studies Consortium recommends yearly transvaginal ultrasound timed to avoid ovulation and annual measurement of serum cancer antigen 125 levels beginning at age 25 years
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Surgery_Schwartz. 56001/03/19 5:04 PM 561THE BREASTCHAPTER 17older.115 Tamoxifen appears to be more effective at preventing estrogen receptor-positive breast cancers.The risk of ovarian cancer in BRCA1 and BRCA2 muta-tion carriers ranges from 20% to 40%, which is 10 times higher than that in the general population. Risk-reducing salpingo-oophorectomy is a reasonable prevention option in mutation carriers. In women with a documented BRCA1 or BRCA2 mutation, consideration for bilateral risk-reducing salpingo-oophorectomy should be between the ages of 35 and 40 years at the completion of childbearing. Removing the ovaries reduces the risk of ovarian cancer and breast cancer when per-formed in premenopausal BRCA mutation carriers. Hormone replacement therapy is discussed with the patient at the time of oophorectomy. The Cancer Genetics Studies Consortium recommends yearly transvaginal ultrasound timed to avoid ovulation and annual measurement of serum cancer antigen 125 levels beginning at age 25 years
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Surgery_Schwartz_3817
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Surgery_Schwartz
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The Cancer Genetics Studies Consortium recommends yearly transvaginal ultrasound timed to avoid ovulation and annual measurement of serum cancer antigen 125 levels beginning at age 25 years as the best screening modalities for ovarian carcinoma in BRCA mutation carriers who have opted to defer risk-reducing surgery.PALB2 (partner and localizer of BRCA2) has recently been characterized as a potential high-risk gene for breast cancer. PALB2 allows nuclear localization of BRCA2 and provides a scaffold for the BRCA1–PALB2–BRCA2 complex. Analysis by Antoniou et al has suggested that the risk of breast cancer for PALB2 mutation carriers is as high as that of BRCA2 mutation carriers.116 The absolute risk of breast cancer for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25–44) for those with no family history of breast cancer to 58% (95% CI, 50–66) for those with two or more first-degree relatives with breast cancer at 50 years of age. The risk of breast cancer
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Surgery_Schwartz. The Cancer Genetics Studies Consortium recommends yearly transvaginal ultrasound timed to avoid ovulation and annual measurement of serum cancer antigen 125 levels beginning at age 25 years as the best screening modalities for ovarian carcinoma in BRCA mutation carriers who have opted to defer risk-reducing surgery.PALB2 (partner and localizer of BRCA2) has recently been characterized as a potential high-risk gene for breast cancer. PALB2 allows nuclear localization of BRCA2 and provides a scaffold for the BRCA1–PALB2–BRCA2 complex. Analysis by Antoniou et al has suggested that the risk of breast cancer for PALB2 mutation carriers is as high as that of BRCA2 mutation carriers.116 The absolute risk of breast cancer for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25–44) for those with no family history of breast cancer to 58% (95% CI, 50–66) for those with two or more first-degree relatives with breast cancer at 50 years of age. The risk of breast cancer
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Surgery_Schwartz_3818
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Surgery_Schwartz
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CI, 25–44) for those with no family history of breast cancer to 58% (95% CI, 50–66) for those with two or more first-degree relatives with breast cancer at 50 years of age. The risk of breast cancer for female PALB2 mutation carriers, depending on the age, was about five to nine times as high compared with the gen-eral population. While screening with mammogram along with MRI has been suggested for PALB2 mutation carriers starting at age 30 with consideration of risk-reducing mastectomy, there is currently insufficient evidence regarding the risk of ovarian cancer and its management.Other hereditary syndromes associated with an increased risk of breast cancer include Cowden disease (PTEN mutations, in which cancers of the thyroid, GI tract, and benign skin and subcutaneous nodules are also seen), Li-Fraumeni syndrome (TP53 mutations, also associated with sarcomas, lymphomas, and adrenocortical tumors), hereditary diffuse gastric cancer syndrome (CDH1 mutations, associated with diffuse
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Surgery_Schwartz. CI, 25–44) for those with no family history of breast cancer to 58% (95% CI, 50–66) for those with two or more first-degree relatives with breast cancer at 50 years of age. The risk of breast cancer for female PALB2 mutation carriers, depending on the age, was about five to nine times as high compared with the gen-eral population. While screening with mammogram along with MRI has been suggested for PALB2 mutation carriers starting at age 30 with consideration of risk-reducing mastectomy, there is currently insufficient evidence regarding the risk of ovarian cancer and its management.Other hereditary syndromes associated with an increased risk of breast cancer include Cowden disease (PTEN mutations, in which cancers of the thyroid, GI tract, and benign skin and subcutaneous nodules are also seen), Li-Fraumeni syndrome (TP53 mutations, also associated with sarcomas, lymphomas, and adrenocortical tumors), hereditary diffuse gastric cancer syndrome (CDH1 mutations, associated with diffuse
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Surgery_Schwartz_3819
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Surgery_Schwartz
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seen), Li-Fraumeni syndrome (TP53 mutations, also associated with sarcomas, lymphomas, and adrenocortical tumors), hereditary diffuse gastric cancer syndrome (CDH1 mutations, associated with diffuse gastric cancer and lobular breast cancers), and syndromes of breast and melanoma. With the discovery of additional genes related to breast cancer susceptibility, panel testing is available for a number of genes in addition to BRCA1 and BRCA2. The inter-pretation of results is complex and is best done with a genetic counselor.EPIDEMIOLOGY AND NATURAL HISTORY OF BREAST CANCEREpidemiologyBreast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women age 20 to 59 years. Based on Surveillance, Epidemiology, and End Results registries (SEER) data, 266,120 new cases were esti-mated in 2018 with 40,920 estimated deaths attributed to breast cancers.117 It accounts for 30% of all newly diagnosed cancers in women and is responsible for 14% of
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Surgery_Schwartz. seen), Li-Fraumeni syndrome (TP53 mutations, also associated with sarcomas, lymphomas, and adrenocortical tumors), hereditary diffuse gastric cancer syndrome (CDH1 mutations, associated with diffuse gastric cancer and lobular breast cancers), and syndromes of breast and melanoma. With the discovery of additional genes related to breast cancer susceptibility, panel testing is available for a number of genes in addition to BRCA1 and BRCA2. The inter-pretation of results is complex and is best done with a genetic counselor.EPIDEMIOLOGY AND NATURAL HISTORY OF BREAST CANCEREpidemiologyBreast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women age 20 to 59 years. Based on Surveillance, Epidemiology, and End Results registries (SEER) data, 266,120 new cases were esti-mated in 2018 with 40,920 estimated deaths attributed to breast cancers.117 It accounts for 30% of all newly diagnosed cancers in women and is responsible for 14% of
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Surgery_Schwartz_3820
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data, 266,120 new cases were esti-mated in 2018 with 40,920 estimated deaths attributed to breast cancers.117 It accounts for 30% of all newly diagnosed cancers in women and is responsible for 14% of the cancer-related deaths in women.Breast cancer was the leading cause of cancer-related mortality in women until 1987, when it was surpassed by lung cancer. In the 1970s, the probability that a woman in the United States would develop breast cancer at some point in her lifetime was estimated at 1 in 13; in 1980 it was 1 in 11; and in 2004 it was 1 in 8. Cancer registries in Connecticut and upper New York State document that the age-adjusted incidence of new breast cancer cases had steadily increased since the mid-1940s. The incidence in the United States, based on data from nine SEER registries, has been decreasing by 23% per year since 2000. The increase had been approximately 1% per year from 1973 to 1980, and there was an additional increase in inci-dence of 4% between 1980 and 1987,
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Surgery_Schwartz. data, 266,120 new cases were esti-mated in 2018 with 40,920 estimated deaths attributed to breast cancers.117 It accounts for 30% of all newly diagnosed cancers in women and is responsible for 14% of the cancer-related deaths in women.Breast cancer was the leading cause of cancer-related mortality in women until 1987, when it was surpassed by lung cancer. In the 1970s, the probability that a woman in the United States would develop breast cancer at some point in her lifetime was estimated at 1 in 13; in 1980 it was 1 in 11; and in 2004 it was 1 in 8. Cancer registries in Connecticut and upper New York State document that the age-adjusted incidence of new breast cancer cases had steadily increased since the mid-1940s. The incidence in the United States, based on data from nine SEER registries, has been decreasing by 23% per year since 2000. The increase had been approximately 1% per year from 1973 to 1980, and there was an additional increase in inci-dence of 4% between 1980 and 1987,
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has been decreasing by 23% per year since 2000. The increase had been approximately 1% per year from 1973 to 1980, and there was an additional increase in inci-dence of 4% between 1980 and 1987, which was characterized by frequent detection of small primary cancers. The increase in breast cancer incidence occurred primarily in women age ≥55 years and paralleled a marked increase in the percentage of older women who had mammograms taken. At the same time, incidence rates for regional metastatic disease dropped and breast cancer mortality declined. From 1960 to 1963, 5-year overall survival rates for breast cancer were 63% and 46% in white and African American women, respectively, whereas the rates for 1981 to 1983 were 78% and 64%, respectively. For 2002 to 2008 rates were 92% and 78%, respectively.There is a 10-fold variation in breast cancer incidence among different countries worldwide. Cyprus and Malta have the highest age-adjusted mortality for breast cancer (29.6 per 100,000
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Surgery_Schwartz. has been decreasing by 23% per year since 2000. The increase had been approximately 1% per year from 1973 to 1980, and there was an additional increase in inci-dence of 4% between 1980 and 1987, which was characterized by frequent detection of small primary cancers. The increase in breast cancer incidence occurred primarily in women age ≥55 years and paralleled a marked increase in the percentage of older women who had mammograms taken. At the same time, incidence rates for regional metastatic disease dropped and breast cancer mortality declined. From 1960 to 1963, 5-year overall survival rates for breast cancer were 63% and 46% in white and African American women, respectively, whereas the rates for 1981 to 1983 were 78% and 64%, respectively. For 2002 to 2008 rates were 92% and 78%, respectively.There is a 10-fold variation in breast cancer incidence among different countries worldwide. Cyprus and Malta have the highest age-adjusted mortality for breast cancer (29.6 per 100,000
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respectively.There is a 10-fold variation in breast cancer incidence among different countries worldwide. Cyprus and Malta have the highest age-adjusted mortality for breast cancer (29.6 per 100,000 population), whereas Haiti has the lowest (2.0 deaths per 100,000 population). The United States has an age-adjusted mortality for breast cancer of 19.0 cases per 100,000 population. Women living in less industrialized nations tend to have a lower incidence of breast cancer than women living in industrialized countries, although Japan is an exception. In the United States, Mormons, Seventh Day Adventists, American Indians, Alaska natives, Hispanic/Latina Americans, and Japanese and Filipino women living in Hawaii have a below-average incidence of breast cancer, whereas nuns (due to nulliparity) and Ashkenazi Jewish women have an above-average incidence.The incidence rates of breast cancer increased in most countries through the 1990s. Since the estimates for 1990, there was an overall
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Surgery_Schwartz. respectively.There is a 10-fold variation in breast cancer incidence among different countries worldwide. Cyprus and Malta have the highest age-adjusted mortality for breast cancer (29.6 per 100,000 population), whereas Haiti has the lowest (2.0 deaths per 100,000 population). The United States has an age-adjusted mortality for breast cancer of 19.0 cases per 100,000 population. Women living in less industrialized nations tend to have a lower incidence of breast cancer than women living in industrialized countries, although Japan is an exception. In the United States, Mormons, Seventh Day Adventists, American Indians, Alaska natives, Hispanic/Latina Americans, and Japanese and Filipino women living in Hawaii have a below-average incidence of breast cancer, whereas nuns (due to nulliparity) and Ashkenazi Jewish women have an above-average incidence.The incidence rates of breast cancer increased in most countries through the 1990s. Since the estimates for 1990, there was an overall
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and Ashkenazi Jewish women have an above-average incidence.The incidence rates of breast cancer increased in most countries through the 1990s. Since the estimates for 1990, there was an overall increase in incidence rates of approximately 0.5% annually. It was predicted that there would be approxi-mately 1.4 million new cases in 2010. The cancer registries in China have noted annual increases in incidence of up to 3% to 4%, and in eastern Asia, increases are similar.Data from the SEER program reveal declines in breast cancer incidence over the past decade, and this is widely attrib-uted to decreased use of hormone replacement therapy as a con-sequence of the Women’s Health Initiative reports.118Breast cancer burden has well-defined variations by geog-raphy, regional lifestyle, and racial or ethnic background.119 In general, both breast cancer incidence and mortality are rela-tively lower among the female populations of Asia and Africa, relatively underdeveloped nations, and nations
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Surgery_Schwartz. and Ashkenazi Jewish women have an above-average incidence.The incidence rates of breast cancer increased in most countries through the 1990s. Since the estimates for 1990, there was an overall increase in incidence rates of approximately 0.5% annually. It was predicted that there would be approxi-mately 1.4 million new cases in 2010. The cancer registries in China have noted annual increases in incidence of up to 3% to 4%, and in eastern Asia, increases are similar.Data from the SEER program reveal declines in breast cancer incidence over the past decade, and this is widely attrib-uted to decreased use of hormone replacement therapy as a con-sequence of the Women’s Health Initiative reports.118Breast cancer burden has well-defined variations by geog-raphy, regional lifestyle, and racial or ethnic background.119 In general, both breast cancer incidence and mortality are rela-tively lower among the female populations of Asia and Africa, relatively underdeveloped nations, and nations
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or ethnic background.119 In general, both breast cancer incidence and mortality are rela-tively lower among the female populations of Asia and Africa, relatively underdeveloped nations, and nations that have not adopted Westernized reproductive and dietary patterns. In contrast, European and North American women and women from heavily industrialized or Westernized countries have a substantially higher breast cancer burden. These international patterns are mirrored in breast cancer incidence and mortality rates observed for the racially, ethnically, and culturally diverse population of the United States.120Brunicardi_Ch17_p0541-p0612.indd 56101/03/19 5:04 PM 562SPECIFIC CONSIDERATIONSPART II10090807060504030201083%68%54%41%Middlesex Hospital 1805-1933 (250 cases)86%66%44%28%18%9%3.6%2%0.8%1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Median survival 2.7 years Natural survivalSurvival untreated casesDuration of life from onset of symptoms
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Surgery_Schwartz. or ethnic background.119 In general, both breast cancer incidence and mortality are rela-tively lower among the female populations of Asia and Africa, relatively underdeveloped nations, and nations that have not adopted Westernized reproductive and dietary patterns. In contrast, European and North American women and women from heavily industrialized or Westernized countries have a substantially higher breast cancer burden. These international patterns are mirrored in breast cancer incidence and mortality rates observed for the racially, ethnically, and culturally diverse population of the United States.120Brunicardi_Ch17_p0541-p0612.indd 56101/03/19 5:04 PM 562SPECIFIC CONSIDERATIONSPART II10090807060504030201083%68%54%41%Middlesex Hospital 1805-1933 (250 cases)86%66%44%28%18%9%3.6%2%0.8%1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Median survival 2.7 years Natural survivalSurvival untreated casesDuration of life from onset of symptoms
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2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Median survival 2.7 years Natural survivalSurvival untreated casesDuration of life from onset of symptoms (years)% SurvivalFigure 17-13. Survival of women with untreated breast cancer compared with natural survival. (Reproduced with permission from Bloom HJG, Richardson WW, Harries EJ: Natural history of untreated breast cancer (1805-1933). Comparison of untreated and treated cases according to histological grade of malignancy, Br Med J. 1962 Jul 28;2(5299):213-221.)Although often related, the factors that influence breast cancer incidence may differ from those that affect mortality. Incidence rates are lower among populations that are heavily weighted with women who begin childbearing at young ages and who have multiple full-term pregnancies followed by pro-longed lactation. These are features that characterize many underdeveloped nations and also many eastern nations. Breast cancer mortality rates
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Surgery_Schwartz. 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Median survival 2.7 years Natural survivalSurvival untreated casesDuration of life from onset of symptoms (years)% SurvivalFigure 17-13. Survival of women with untreated breast cancer compared with natural survival. (Reproduced with permission from Bloom HJG, Richardson WW, Harries EJ: Natural history of untreated breast cancer (1805-1933). Comparison of untreated and treated cases according to histological grade of malignancy, Br Med J. 1962 Jul 28;2(5299):213-221.)Although often related, the factors that influence breast cancer incidence may differ from those that affect mortality. Incidence rates are lower among populations that are heavily weighted with women who begin childbearing at young ages and who have multiple full-term pregnancies followed by pro-longed lactation. These are features that characterize many underdeveloped nations and also many eastern nations. Breast cancer mortality rates
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who have multiple full-term pregnancies followed by pro-longed lactation. These are features that characterize many underdeveloped nations and also many eastern nations. Breast cancer mortality rates should be lower in populations that have a lower incidence, but the mortality burden will simultaneously be adversely affected by the absence of effective mammographic screening programs for early detection and diminished access to multidisciplinary cancer treatment programs. These features are likely to account for much of the disproportionate mortal-ity risks that are seen in underdeveloped nations. Similar fac-tors probably account for differences in breast cancer burden observed among the various racial and ethnic groups within the United States. Interestingly, breast cancer incidence and mortality rates rise among secondand third-generation Asian Americans as they adopt Western lifestyles.Disparities in breast cancer survival among subsets of the American population are generating
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Surgery_Schwartz. who have multiple full-term pregnancies followed by pro-longed lactation. These are features that characterize many underdeveloped nations and also many eastern nations. Breast cancer mortality rates should be lower in populations that have a lower incidence, but the mortality burden will simultaneously be adversely affected by the absence of effective mammographic screening programs for early detection and diminished access to multidisciplinary cancer treatment programs. These features are likely to account for much of the disproportionate mortal-ity risks that are seen in underdeveloped nations. Similar fac-tors probably account for differences in breast cancer burden observed among the various racial and ethnic groups within the United States. Interestingly, breast cancer incidence and mortality rates rise among secondand third-generation Asian Americans as they adopt Western lifestyles.Disparities in breast cancer survival among subsets of the American population are generating
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Surgery_Schwartz_3827
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mortality rates rise among secondand third-generation Asian Americans as they adopt Western lifestyles.Disparities in breast cancer survival among subsets of the American population are generating increased publicity because they are closely linked to disparities in socioeconomic status. Poverty rates and proportions of the population that lack health care insurance are two to three times higher among minority racial and ethnic groups such as African Americans and His-panic/Latino Americans. These socioeconomic disadvantages create barriers to effective breast cancer screening and result in delayed breast cancer diagnosis, advanced stage distribu-tion, inadequacies in comprehensive treatment, and, ultimately, increased mortality rates. Furthermore, the rapid growth in the Hispanic population is accompanied by increasing problems in health education because of linguistic barriers between physi-cians and recently immigrated, non–English-speaking patients. Recent studies also are
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Surgery_Schwartz. mortality rates rise among secondand third-generation Asian Americans as they adopt Western lifestyles.Disparities in breast cancer survival among subsets of the American population are generating increased publicity because they are closely linked to disparities in socioeconomic status. Poverty rates and proportions of the population that lack health care insurance are two to three times higher among minority racial and ethnic groups such as African Americans and His-panic/Latino Americans. These socioeconomic disadvantages create barriers to effective breast cancer screening and result in delayed breast cancer diagnosis, advanced stage distribu-tion, inadequacies in comprehensive treatment, and, ultimately, increased mortality rates. Furthermore, the rapid growth in the Hispanic population is accompanied by increasing problems in health education because of linguistic barriers between physi-cians and recently immigrated, non–English-speaking patients. Recent studies also are
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population is accompanied by increasing problems in health education because of linguistic barriers between physi-cians and recently immigrated, non–English-speaking patients. Recent studies also are documenting inequities in the treatments delivered to minority breast cancer patients, such as increased rates of failure to provide systemic therapy, use of sentinel lymph node dissection, and breast reconstruction. Some of the treatment delivery disparities are related to inadequately con-trolled comorbidities (such as hypertension and diabetes), which are more prevalent in minority populations. However, some studies that adjust for these factors report persistent and unex-plained unevenness in treatment recommendations. It is clear that breast cancer disparities associated with racial or ethnic background have a multifactorial cause, and improvements in outcome will require correction of many public health problems at both the patient and provider levels.Advances in the ability to
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Surgery_Schwartz. population is accompanied by increasing problems in health education because of linguistic barriers between physi-cians and recently immigrated, non–English-speaking patients. Recent studies also are documenting inequities in the treatments delivered to minority breast cancer patients, such as increased rates of failure to provide systemic therapy, use of sentinel lymph node dissection, and breast reconstruction. Some of the treatment delivery disparities are related to inadequately con-trolled comorbidities (such as hypertension and diabetes), which are more prevalent in minority populations. However, some studies that adjust for these factors report persistent and unex-plained unevenness in treatment recommendations. It is clear that breast cancer disparities associated with racial or ethnic background have a multifactorial cause, and improvements in outcome will require correction of many public health problems at both the patient and provider levels.Advances in the ability to
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or ethnic background have a multifactorial cause, and improvements in outcome will require correction of many public health problems at both the patient and provider levels.Advances in the ability to characterize breast cancer sub-types and the genetics of the disease are now provoking specula-tion regarding possible hereditary influences on breast cancer risk that are related to racial or ethnic ancestry.121 These questions become particularly compelling when one looks at disparities in breast cancer burden between African Americans and Cau-casians. Lifetime risk of breast cancer is lower for African Americans, yet a paradoxically increased breast cancer mortal-ity risk also is seen. African Americans also have a younger age distribution for breast cancer; among women <45 years of age, breast cancer incidence is highest among African Americans compared to other subsets of the American population. Lastly and most provocatively, African American women of all ages have notably higher
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Surgery_Schwartz. or ethnic background have a multifactorial cause, and improvements in outcome will require correction of many public health problems at both the patient and provider levels.Advances in the ability to characterize breast cancer sub-types and the genetics of the disease are now provoking specula-tion regarding possible hereditary influences on breast cancer risk that are related to racial or ethnic ancestry.121 These questions become particularly compelling when one looks at disparities in breast cancer burden between African Americans and Cau-casians. Lifetime risk of breast cancer is lower for African Americans, yet a paradoxically increased breast cancer mortal-ity risk also is seen. African Americans also have a younger age distribution for breast cancer; among women <45 years of age, breast cancer incidence is highest among African Americans compared to other subsets of the American population. Lastly and most provocatively, African American women of all ages have notably higher
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breast cancer incidence is highest among African Americans compared to other subsets of the American population. Lastly and most provocatively, African American women of all ages have notably higher incidence rates for estrogen receptor-negative tumors. These same patterns of disease are seen in con-temporary female populations of western, sub-Saharan Africa, who are likely to share ancestry with African American women as a consequence of the Colonial-era slave trade. Interestingly, male breast cancer also is seen with increased frequency among both African Americans and Africans.Natural HistoryBloom and colleagues described the natural history of breast cancer based on the records of 250 women with untreated breast cancers who were cared for on charity wards in the Middlesex Hospital, London, between 1805 and 1933. The median survival of this population was 2.7 years after initial diagnosis (Fig. 17-13).122 The 5and 10-year survival rates for these women were 18.0% and 3.6%,
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Surgery_Schwartz. breast cancer incidence is highest among African Americans compared to other subsets of the American population. Lastly and most provocatively, African American women of all ages have notably higher incidence rates for estrogen receptor-negative tumors. These same patterns of disease are seen in con-temporary female populations of western, sub-Saharan Africa, who are likely to share ancestry with African American women as a consequence of the Colonial-era slave trade. Interestingly, male breast cancer also is seen with increased frequency among both African Americans and Africans.Natural HistoryBloom and colleagues described the natural history of breast cancer based on the records of 250 women with untreated breast cancers who were cared for on charity wards in the Middlesex Hospital, London, between 1805 and 1933. The median survival of this population was 2.7 years after initial diagnosis (Fig. 17-13).122 The 5and 10-year survival rates for these women were 18.0% and 3.6%,
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London, between 1805 and 1933. The median survival of this population was 2.7 years after initial diagnosis (Fig. 17-13).122 The 5and 10-year survival rates for these women were 18.0% and 3.6%, respectively. Only 0.8% survived for 15 years or longer. Autopsy data confirmed that 95% of these women died of breast cancer, whereas the remaining 5% died of other causes. Almost 75% of the women developed ulcer-ation of the breast during the course of the disease. The longest surviving patient died in the 19th year after diagnosis.Primary Breast Cancer. More than 80% of breast cancers show productive fibrosis that involves the epithelial and stro-mal tissues. With growth of the cancer and invasion of the surrounding breast tissues, the accompanying desmoplastic response entraps and shortens Cooper’s suspensory ligaments to produce a characteristic skin retraction. Localized edema (peau d’orange) develops when drainage of lymph fluid from the skin is disrupted. With continued growth, cancer
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Surgery_Schwartz. London, between 1805 and 1933. The median survival of this population was 2.7 years after initial diagnosis (Fig. 17-13).122 The 5and 10-year survival rates for these women were 18.0% and 3.6%, respectively. Only 0.8% survived for 15 years or longer. Autopsy data confirmed that 95% of these women died of breast cancer, whereas the remaining 5% died of other causes. Almost 75% of the women developed ulcer-ation of the breast during the course of the disease. The longest surviving patient died in the 19th year after diagnosis.Primary Breast Cancer. More than 80% of breast cancers show productive fibrosis that involves the epithelial and stro-mal tissues. With growth of the cancer and invasion of the surrounding breast tissues, the accompanying desmoplastic response entraps and shortens Cooper’s suspensory ligaments to produce a characteristic skin retraction. Localized edema (peau d’orange) develops when drainage of lymph fluid from the skin is disrupted. With continued growth, cancer
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suspensory ligaments to produce a characteristic skin retraction. Localized edema (peau d’orange) develops when drainage of lymph fluid from the skin is disrupted. With continued growth, cancer cells invade the skin, and eventually ulceration occurs. As new areas of skin are invaded, small satellite nodules appear near the primary ulceration. The size of the primary breast cancer correlates with disease-free and overall survival, but there is a close associa-tion between cancer size and axillary lymph node involvement (Fig. 17-14). In general, up to 20% of breast cancer recurrences are local-regional, >60% are distant, and 20% are both local-regional and distant.Brunicardi_Ch17_p0541-p0612.indd 56201/03/19 5:04 PM 563THE BREASTCHAPTER 17xxxxxxxxxx**********Diameter (cm)0.980.950.900.800.700.600.500.400.300.20Proportion of patients with metastases10100Volume (ml)2345676891011100908070605040302010Percent survivors31529717363653126317714265321234909214425N + >3 (183)N + (381)N + 1
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Surgery_Schwartz. suspensory ligaments to produce a characteristic skin retraction. Localized edema (peau d’orange) develops when drainage of lymph fluid from the skin is disrupted. With continued growth, cancer cells invade the skin, and eventually ulceration occurs. As new areas of skin are invaded, small satellite nodules appear near the primary ulceration. The size of the primary breast cancer correlates with disease-free and overall survival, but there is a close associa-tion between cancer size and axillary lymph node involvement (Fig. 17-14). In general, up to 20% of breast cancer recurrences are local-regional, >60% are distant, and 20% are both local-regional and distant.Brunicardi_Ch17_p0541-p0612.indd 56201/03/19 5:04 PM 563THE BREASTCHAPTER 17xxxxxxxxxx**********Diameter (cm)0.980.950.900.800.700.600.500.400.300.20Proportion of patients with metastases10100Volume (ml)2345676891011100908070605040302010Percent survivors31529717363653126317714265321234909214425N + >3 (183)N + (381)N + 1
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of patients with metastases10100Volume (ml)2345676891011100908070605040302010Percent survivors31529717363653126317714265321234909214425N + >3 (183)N + (381)N + 1 (198)N (335)Whole series (716)241068Years after mastectomyABFigure 17-14. A. Overall survival for women with breast cancer according to axillary lymph node status. The time periods are years after radical mastectomy. (Reproduced with permission from Vala-gussa P, Bonadonna G, Veronesi U, et al: Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients, Cancer. 1978 Mar;41(3):1170-1178.) B. Risk of metasta-ses according to breast cancer volume and diameter. (Reproduced with permission from Koscielny S, Tubiana M, Lê MG, et al: Breast cancer: Relationship between the size of the primary tumour and the probability of metastatic dissemination, Br J Cancer. 1984 Jun;49(6):709-715.)Axillary Lymph Node Metastases. As the size of the pri-mary breast cancer increases, some cancer cells are
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Surgery_Schwartz. of patients with metastases10100Volume (ml)2345676891011100908070605040302010Percent survivors31529717363653126317714265321234909214425N + >3 (183)N + (381)N + 1 (198)N (335)Whole series (716)241068Years after mastectomyABFigure 17-14. A. Overall survival for women with breast cancer according to axillary lymph node status. The time periods are years after radical mastectomy. (Reproduced with permission from Vala-gussa P, Bonadonna G, Veronesi U, et al: Patterns of relapse and survival following radical mastectomy. Analysis of 716 consecutive patients, Cancer. 1978 Mar;41(3):1170-1178.) B. Risk of metasta-ses according to breast cancer volume and diameter. (Reproduced with permission from Koscielny S, Tubiana M, Lê MG, et al: Breast cancer: Relationship between the size of the primary tumour and the probability of metastatic dissemination, Br J Cancer. 1984 Jun;49(6):709-715.)Axillary Lymph Node Metastases. As the size of the pri-mary breast cancer increases, some cancer cells are
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tumour and the probability of metastatic dissemination, Br J Cancer. 1984 Jun;49(6):709-715.)Axillary Lymph Node Metastases. As the size of the pri-mary breast cancer increases, some cancer cells are shed into cellular spaces and transported via the lymphatic network of the breast to the regional lymph nodes, especially the axillary lymph nodes. Lymph nodes that contain metastatic cancer are at first ill-defined and soft but become firm or hard with con-tinued growth of the metastatic cancer. Eventually the lymph nodes adhere to each other and form a conglomerate mass. Cancer cells may grow through the lymph node capsule and fix to contiguous structures in the axilla, including the chest wall. Typically, axillary lymph nodes are involved sequentially from the low (level I) to the central (level II) to the apical (level III) lymph node groups. Approximately 95% of the women who die of breast cancer have distant metastases, and traditionally the most important prognostic correlate of
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Surgery_Schwartz. tumour and the probability of metastatic dissemination, Br J Cancer. 1984 Jun;49(6):709-715.)Axillary Lymph Node Metastases. As the size of the pri-mary breast cancer increases, some cancer cells are shed into cellular spaces and transported via the lymphatic network of the breast to the regional lymph nodes, especially the axillary lymph nodes. Lymph nodes that contain metastatic cancer are at first ill-defined and soft but become firm or hard with con-tinued growth of the metastatic cancer. Eventually the lymph nodes adhere to each other and form a conglomerate mass. Cancer cells may grow through the lymph node capsule and fix to contiguous structures in the axilla, including the chest wall. Typically, axillary lymph nodes are involved sequentially from the low (level I) to the central (level II) to the apical (level III) lymph node groups. Approximately 95% of the women who die of breast cancer have distant metastases, and traditionally the most important prognostic correlate of
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(level II) to the apical (level III) lymph node groups. Approximately 95% of the women who die of breast cancer have distant metastases, and traditionally the most important prognostic correlate of disease-free and over-all survival was axillary lymph node status (see Fig. 17-14A). Women with node-negative disease had less than a 30% risk of recurrence, compared with as much as a 75% risk for women with node-positive disease.Distant Metastases. At approximately the 20th cell dou-bling, breast cancers acquire their own blood supply (neovas-cularization). Thereafter, cancer cells may be shed directly into the systemic venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson’s plexus of veins, which courses the length of the vertebral column. These cells are scavenged by natural killer lymphocytes and macrophages. Successful implantation of metastatic foci from breast cancer predictably occurs after the primary cancer
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Surgery_Schwartz. (level II) to the apical (level III) lymph node groups. Approximately 95% of the women who die of breast cancer have distant metastases, and traditionally the most important prognostic correlate of disease-free and over-all survival was axillary lymph node status (see Fig. 17-14A). Women with node-negative disease had less than a 30% risk of recurrence, compared with as much as a 75% risk for women with node-positive disease.Distant Metastases. At approximately the 20th cell dou-bling, breast cancers acquire their own blood supply (neovas-cularization). Thereafter, cancer cells may be shed directly into the systemic venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson’s plexus of veins, which courses the length of the vertebral column. These cells are scavenged by natural killer lymphocytes and macrophages. Successful implantation of metastatic foci from breast cancer predictably occurs after the primary cancer
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vertebral column. These cells are scavenged by natural killer lymphocytes and macrophages. Successful implantation of metastatic foci from breast cancer predictably occurs after the primary cancer exceeds 0.5 cm in diameter, which corresponds to the 27th cell doubling. For 10 years after initial treatment, distant metastases are the most common cause of death in breast cancer patients. For this reason, conclusive results cannot be derived from breast cancer trials until at least 5 to 10 years have elapsed. Although 60% of the women who develop distant metastases will do so within 60 months of treatment, metastases may become evident as late as 20 to 30 years after treatment of the primary cancer.123 Patients with estrogen receptor nega-tive breast cancers are proportionately more likely to develop recurrence in the first 3 to 5 years, whereas those with estrogen receptor positive tumors have a risk of developing recurrence, which drops off more slowly beyond 5 years than is seen with
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Surgery_Schwartz. vertebral column. These cells are scavenged by natural killer lymphocytes and macrophages. Successful implantation of metastatic foci from breast cancer predictably occurs after the primary cancer exceeds 0.5 cm in diameter, which corresponds to the 27th cell doubling. For 10 years after initial treatment, distant metastases are the most common cause of death in breast cancer patients. For this reason, conclusive results cannot be derived from breast cancer trials until at least 5 to 10 years have elapsed. Although 60% of the women who develop distant metastases will do so within 60 months of treatment, metastases may become evident as late as 20 to 30 years after treatment of the primary cancer.123 Patients with estrogen receptor nega-tive breast cancers are proportionately more likely to develop recurrence in the first 3 to 5 years, whereas those with estrogen receptor positive tumors have a risk of developing recurrence, which drops off more slowly beyond 5 years than is seen with
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develop recurrence in the first 3 to 5 years, whereas those with estrogen receptor positive tumors have a risk of developing recurrence, which drops off more slowly beyond 5 years than is seen with ER-negative tumors.124 Recently, a report showed that tumor size and nodal status remain powerful predictors of late recur-rences compared to more recently developed tools such as the immunohistochemical score (IHC4) and two gene expression profile tests (Recurrence Score and PAM50).125 Common sites of involvement, in order of frequency, are bone, lung, pleura, soft tissues, and liver. Brain metastases are less frequent over-all, although with the advent of adjuvant systemic therapies it has been reported that CNS disease may be seen earlier.126,127 There are also reports of factors that are associated with the risk of developing brain metastases.128 For example, they are more likely to be seen in patients with triple receptor negative breast cancer (ER-negative, PR-negative, and
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Surgery_Schwartz. develop recurrence in the first 3 to 5 years, whereas those with estrogen receptor positive tumors have a risk of developing recurrence, which drops off more slowly beyond 5 years than is seen with ER-negative tumors.124 Recently, a report showed that tumor size and nodal status remain powerful predictors of late recur-rences compared to more recently developed tools such as the immunohistochemical score (IHC4) and two gene expression profile tests (Recurrence Score and PAM50).125 Common sites of involvement, in order of frequency, are bone, lung, pleura, soft tissues, and liver. Brain metastases are less frequent over-all, although with the advent of adjuvant systemic therapies it has been reported that CNS disease may be seen earlier.126,127 There are also reports of factors that are associated with the risk of developing brain metastases.128 For example, they are more likely to be seen in patients with triple receptor negative breast cancer (ER-negative, PR-negative, and
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are associated with the risk of developing brain metastases.128 For example, they are more likely to be seen in patients with triple receptor negative breast cancer (ER-negative, PR-negative, and HER2-negative) or patients with HER2-positive breast cancer who have received chemotherapy and HER2-directed therapies.HISTOPATHOLOGY OF BREAST CANCERCarcinoma In SituCancer cells are in situ or invasive depending on whether or not they invade through the basement membrane.129,130 Broders’s original description of in situ breast cancer stressed the absence of invasion of cells into the surrounding stroma and their confine-ment within natural ductal and alveolar boundaries.129 Because areas of invasion may be minute, the accurate diagnosis of in situ cancer necessitates the analysis of multiple microscopic sec-tions to exclude invasion. In 1941, Foote and Stewart published Brunicardi_Ch17_p0541-p0612.indd 56301/03/19 5:04 PM 564SPECIFIC CONSIDERATIONSPART IITable 17-8Salient
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Surgery_Schwartz. are associated with the risk of developing brain metastases.128 For example, they are more likely to be seen in patients with triple receptor negative breast cancer (ER-negative, PR-negative, and HER2-negative) or patients with HER2-positive breast cancer who have received chemotherapy and HER2-directed therapies.HISTOPATHOLOGY OF BREAST CANCERCarcinoma In SituCancer cells are in situ or invasive depending on whether or not they invade through the basement membrane.129,130 Broders’s original description of in situ breast cancer stressed the absence of invasion of cells into the surrounding stroma and their confine-ment within natural ductal and alveolar boundaries.129 Because areas of invasion may be minute, the accurate diagnosis of in situ cancer necessitates the analysis of multiple microscopic sec-tions to exclude invasion. In 1941, Foote and Stewart published Brunicardi_Ch17_p0541-p0612.indd 56301/03/19 5:04 PM 564SPECIFIC CONSIDERATIONSPART IITable 17-8Salient
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of multiple microscopic sec-tions to exclude invasion. In 1941, Foote and Stewart published Brunicardi_Ch17_p0541-p0612.indd 56301/03/19 5:04 PM 564SPECIFIC CONSIDERATIONSPART IITable 17-8Salient characteristics of in situ ductal (DCIS) and lobular (LCIS) carcinoma of the breast LCISDCISAge (years)44–4754–58Incidencea2%–5%5%–10%Clinical signsNoneMass, pain, nipple dischargeMammographic signsNoneMicrocalcificationsPremenopausal2/31/3Incidence of synchronous invasive carcinoma5%2%–46%Multicentricity60%–90%40%–80%Bilaterality50%–70%10%–20%Axillary metastasis1%1%–2%Subsequent carcinomas: Incidence25%–35%25%–70% LateralityBilateralIpsilateral Interval to diagnosis15–20 y5–10 y Histologic typeDuctalDuctalaIn biopsy specimens of mammographically detected breast lesions.Reproduced with permission from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Table 17-9Classification of breast ductal
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Surgery_Schwartz. of multiple microscopic sec-tions to exclude invasion. In 1941, Foote and Stewart published Brunicardi_Ch17_p0541-p0612.indd 56301/03/19 5:04 PM 564SPECIFIC CONSIDERATIONSPART IITable 17-8Salient characteristics of in situ ductal (DCIS) and lobular (LCIS) carcinoma of the breast LCISDCISAge (years)44–4754–58Incidencea2%–5%5%–10%Clinical signsNoneMass, pain, nipple dischargeMammographic signsNoneMicrocalcificationsPremenopausal2/31/3Incidence of synchronous invasive carcinoma5%2%–46%Multicentricity60%–90%40%–80%Bilaterality50%–70%10%–20%Axillary metastasis1%1%–2%Subsequent carcinomas: Incidence25%–35%25%–70% LateralityBilateralIpsilateral Interval to diagnosis15–20 y5–10 y Histologic typeDuctalDuctalaIn biopsy specimens of mammographically detected breast lesions.Reproduced with permission from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Table 17-9Classification of breast ductal
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from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Table 17-9Classification of breast ductal carcinoma in situ (DCIS)HISTOLOGIC SUBTYPE DETERMINING CHARACTERISTICSDCIS GRADE NUCLEAR GRADENECROSISComedoHighExtensiveHighIntermediateaIntermediateFocal or absentIntermediateNoncomedobLowAbsentLowaOften a mixture of noncomedo patterns.bSolid, cribriform, papillary, or focal micropapillary.Adapted with permission from Koo JS, Kim MJ, Kim EK, et al: Comparison of immunohistochemical staining in breast papillary neoplasms of cytokeratin 5/6 and p63 in core needle biopsies and surgical excisions, Appl Immunohistochem Mol Morphol. 2012 Mar;20(2):108-115.a landmark description of LCIS, which distinguished it from DCIS.130 In the late 1960s, Gallagher and Martin published their study of whole-breast sections and described a stepwise progres-sion from benign breast tissue to in situ cancer and
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Surgery_Schwartz. from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Table 17-9Classification of breast ductal carcinoma in situ (DCIS)HISTOLOGIC SUBTYPE DETERMINING CHARACTERISTICSDCIS GRADE NUCLEAR GRADENECROSISComedoHighExtensiveHighIntermediateaIntermediateFocal or absentIntermediateNoncomedobLowAbsentLowaOften a mixture of noncomedo patterns.bSolid, cribriform, papillary, or focal micropapillary.Adapted with permission from Koo JS, Kim MJ, Kim EK, et al: Comparison of immunohistochemical staining in breast papillary neoplasms of cytokeratin 5/6 and p63 in core needle biopsies and surgical excisions, Appl Immunohistochem Mol Morphol. 2012 Mar;20(2):108-115.a landmark description of LCIS, which distinguished it from DCIS.130 In the late 1960s, Gallagher and Martin published their study of whole-breast sections and described a stepwise progres-sion from benign breast tissue to in situ cancer and
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it from DCIS.130 In the late 1960s, Gallagher and Martin published their study of whole-breast sections and described a stepwise progres-sion from benign breast tissue to in situ cancer and subsequently to invasive cancer. Before the widespread use of mammography, diagnosis of breast cancer was by physical examination. At that time, in situ cancers constituted <6% of all breast cancers, and LCIS was more frequently diagnosed than DCIS by a ratio of >2:1. However, when screening mammography became popular, a 14-fold increase in the incidence of in situ cancer (45%) was demonstrated, and DCIS was more frequently diagnosed than LCIS by a ratio of >2:1. Table 17-8 lists the clinical and patho-logic characteristics of DCIS and LCIS. Multicentricity refers to the occurrence of a second breast cancer outside the breast quadrant of the primary cancer (or at least 4 cm away), whereas multifocality refers to the occurrence of a second cancer within the same breast quadrant as the primary cancer
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Surgery_Schwartz. it from DCIS.130 In the late 1960s, Gallagher and Martin published their study of whole-breast sections and described a stepwise progres-sion from benign breast tissue to in situ cancer and subsequently to invasive cancer. Before the widespread use of mammography, diagnosis of breast cancer was by physical examination. At that time, in situ cancers constituted <6% of all breast cancers, and LCIS was more frequently diagnosed than DCIS by a ratio of >2:1. However, when screening mammography became popular, a 14-fold increase in the incidence of in situ cancer (45%) was demonstrated, and DCIS was more frequently diagnosed than LCIS by a ratio of >2:1. Table 17-8 lists the clinical and patho-logic characteristics of DCIS and LCIS. Multicentricity refers to the occurrence of a second breast cancer outside the breast quadrant of the primary cancer (or at least 4 cm away), whereas multifocality refers to the occurrence of a second cancer within the same breast quadrant as the primary cancer
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outside the breast quadrant of the primary cancer (or at least 4 cm away), whereas multifocality refers to the occurrence of a second cancer within the same breast quadrant as the primary cancer (or within 4 cm of it). Multicentricity occurs in 60% to 90% of women with LCIS, whereas the rate of multicentricity for DCIS is reported to be 40% to 80%. LCIS occurs bilaterally in 50% to 70% of cases, whereas DCIS occurs bilaterally in 10% to 20% of cases.Lobular Carcinoma In Situ. LCIS originates from the termi-nal duct lobular units and develops only in the female breast. It is characterized by distention and distortion of the terminal duct lobular units by cells that are large but maintain a normal nuclear to cytoplasmic ratio. Cytoplasmic mucoid globules are a distinctive cellular feature. LCIS may be observed in breast tissues that contain microcalcifications, but the calcifications associated with LCIS typically occur in adjacent tissues. This neighborhood calcification is a feature
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Surgery_Schwartz. outside the breast quadrant of the primary cancer (or at least 4 cm away), whereas multifocality refers to the occurrence of a second cancer within the same breast quadrant as the primary cancer (or within 4 cm of it). Multicentricity occurs in 60% to 90% of women with LCIS, whereas the rate of multicentricity for DCIS is reported to be 40% to 80%. LCIS occurs bilaterally in 50% to 70% of cases, whereas DCIS occurs bilaterally in 10% to 20% of cases.Lobular Carcinoma In Situ. LCIS originates from the termi-nal duct lobular units and develops only in the female breast. It is characterized by distention and distortion of the terminal duct lobular units by cells that are large but maintain a normal nuclear to cytoplasmic ratio. Cytoplasmic mucoid globules are a distinctive cellular feature. LCIS may be observed in breast tissues that contain microcalcifications, but the calcifications associated with LCIS typically occur in adjacent tissues. This neighborhood calcification is a feature
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LCIS may be observed in breast tissues that contain microcalcifications, but the calcifications associated with LCIS typically occur in adjacent tissues. This neighborhood calcification is a feature that is unique to LCIS and contributes to its diagnosis. The frequency of LCIS in the general population cannot be reliably determined because it usu-ally presents as an incidental finding. The average age at diag-nosis is 45 years, which is approximately 15 to 25 years younger than the age at diagnosis for invasive breast cancer. LCIS has a distinct racial predilection, occurring 12 times more frequently in white women than in African-American women. Invasive breast cancer develops in 25% to 35% of women with LCIS. Invasive cancer may develop in either breast, regardless of which breast harbored the initial focus of LCIS, and is detected synchronously with LCIS in 5% of cases. In women with a his-tory of LCIS, up to 65% of subsequent invasive cancers are duc-tal, not lobular, in origin.
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Surgery_Schwartz. LCIS may be observed in breast tissues that contain microcalcifications, but the calcifications associated with LCIS typically occur in adjacent tissues. This neighborhood calcification is a feature that is unique to LCIS and contributes to its diagnosis. The frequency of LCIS in the general population cannot be reliably determined because it usu-ally presents as an incidental finding. The average age at diag-nosis is 45 years, which is approximately 15 to 25 years younger than the age at diagnosis for invasive breast cancer. LCIS has a distinct racial predilection, occurring 12 times more frequently in white women than in African-American women. Invasive breast cancer develops in 25% to 35% of women with LCIS. Invasive cancer may develop in either breast, regardless of which breast harbored the initial focus of LCIS, and is detected synchronously with LCIS in 5% of cases. In women with a his-tory of LCIS, up to 65% of subsequent invasive cancers are duc-tal, not lobular, in origin.
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the initial focus of LCIS, and is detected synchronously with LCIS in 5% of cases. In women with a his-tory of LCIS, up to 65% of subsequent invasive cancers are duc-tal, not lobular, in origin. For these reasons, LCIS is regarded as a marker of increased risk for invasive breast cancer rather than as an anatomic precursor. Individuals should be counseled regarding their risk of developing breast cancer and appropriate risk reduction strategies, including observation with screening, chemoprevention, and risk-reducing bilateral mastectomy.Ductal Carcinoma In Situ. Although DCIS is predominantly seen in the female breast, it accounts for 5% of male breast cancers. Published series suggest a detection frequency of 7% in all biopsy tissue specimens. The term intraductal carcinoma is frequently applied to DCIS, which carries a high risk for progres-sion to an invasive cancer. Histologically, DCIS is characterized by a proliferation of the epithelium that lines the minor ducts, resulting in
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Surgery_Schwartz. the initial focus of LCIS, and is detected synchronously with LCIS in 5% of cases. In women with a his-tory of LCIS, up to 65% of subsequent invasive cancers are duc-tal, not lobular, in origin. For these reasons, LCIS is regarded as a marker of increased risk for invasive breast cancer rather than as an anatomic precursor. Individuals should be counseled regarding their risk of developing breast cancer and appropriate risk reduction strategies, including observation with screening, chemoprevention, and risk-reducing bilateral mastectomy.Ductal Carcinoma In Situ. Although DCIS is predominantly seen in the female breast, it accounts for 5% of male breast cancers. Published series suggest a detection frequency of 7% in all biopsy tissue specimens. The term intraductal carcinoma is frequently applied to DCIS, which carries a high risk for progres-sion to an invasive cancer. Histologically, DCIS is characterized by a proliferation of the epithelium that lines the minor ducts, resulting in
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applied to DCIS, which carries a high risk for progres-sion to an invasive cancer. Histologically, DCIS is characterized by a proliferation of the epithelium that lines the minor ducts, resulting in papillary growths within the duct lumina. Early in their development, the cancer cells do not show pleomorphism, mitoses, or atypia, which leads to difficulty in distinguishing early DCIS from benign hyperplasia. The papillary growths (papillary growth pattern) eventually coalesce and fill the duct lumina so that only scattered, rounded spaces remain between the clumps of atypical cancer cells, which show hyperchroma-sia and loss of polarity (cribriform growth pattern). Eventually pleomorphic cancer cells with frequent mitotic figures obliterate the lumina and distend the ducts (solid growth pattern). With continued growth, these cells outstrip their blood supply and become necrotic (comedo growth pattern). Calcium deposition occurs in the areas of necrosis and is a common feature seen on
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Surgery_Schwartz. applied to DCIS, which carries a high risk for progres-sion to an invasive cancer. Histologically, DCIS is characterized by a proliferation of the epithelium that lines the minor ducts, resulting in papillary growths within the duct lumina. Early in their development, the cancer cells do not show pleomorphism, mitoses, or atypia, which leads to difficulty in distinguishing early DCIS from benign hyperplasia. The papillary growths (papillary growth pattern) eventually coalesce and fill the duct lumina so that only scattered, rounded spaces remain between the clumps of atypical cancer cells, which show hyperchroma-sia and loss of polarity (cribriform growth pattern). Eventually pleomorphic cancer cells with frequent mitotic figures obliterate the lumina and distend the ducts (solid growth pattern). With continued growth, these cells outstrip their blood supply and become necrotic (comedo growth pattern). Calcium deposition occurs in the areas of necrosis and is a common feature seen on
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With continued growth, these cells outstrip their blood supply and become necrotic (comedo growth pattern). Calcium deposition occurs in the areas of necrosis and is a common feature seen on mammography. DCIS is now frequently classified based on nuclear grade and the presence of necrosis (Table 17-9). Based Brunicardi_Ch17_p0541-p0612.indd 56401/03/19 5:04 PM 565THE BREASTCHAPTER 17on multiple consensus meetings, grading of DCIS has been rec-ommended. Although there is no universal agreement on clas-sification, most systems endorse the use of cytologic grade and presence or absence of necrosis.131The risk for invasive breast cancer is increased nearly fivefold in women with DCIS.132 The invasive cancers are observed in the ipsilateral breast, usually in the same quadrant as the DCIS that was originally detected, which suggests that DCIS is an anatomic precursor of invasive ductal carcinoma (Fig. 17-15A and B).Invasive Breast CarcinomaInvasive breast cancers have been described as
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Surgery_Schwartz. With continued growth, these cells outstrip their blood supply and become necrotic (comedo growth pattern). Calcium deposition occurs in the areas of necrosis and is a common feature seen on mammography. DCIS is now frequently classified based on nuclear grade and the presence of necrosis (Table 17-9). Based Brunicardi_Ch17_p0541-p0612.indd 56401/03/19 5:04 PM 565THE BREASTCHAPTER 17on multiple consensus meetings, grading of DCIS has been rec-ommended. Although there is no universal agreement on clas-sification, most systems endorse the use of cytologic grade and presence or absence of necrosis.131The risk for invasive breast cancer is increased nearly fivefold in women with DCIS.132 The invasive cancers are observed in the ipsilateral breast, usually in the same quadrant as the DCIS that was originally detected, which suggests that DCIS is an anatomic precursor of invasive ductal carcinoma (Fig. 17-15A and B).Invasive Breast CarcinomaInvasive breast cancers have been described as
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was originally detected, which suggests that DCIS is an anatomic precursor of invasive ductal carcinoma (Fig. 17-15A and B).Invasive Breast CarcinomaInvasive breast cancers have been described as lobular or duc-tal in origin.128-131 Early classifications used the term lobular to describe invasive cancers that were associated with LCIS, whereas all other invasive cancers were referred to as ductal. Current histologic classifications recognize special types of breast cancers (10% of total cases), which are defined by spe-cific histologic features. To qualify as a special-type cancer, at least 90% of the cancer must contain the defining histologic features. About 80% of invasive breast cancers are described as invasive ductal carcinoma of no special type (NST). These can-cers generally have a worse prognosis than special-type cancers. Foote and Stewart originally proposed the following classifica-tion for invasive breast cancer130:1. Paget’s disease of the nipple2. Invasive ductal
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Surgery_Schwartz. was originally detected, which suggests that DCIS is an anatomic precursor of invasive ductal carcinoma (Fig. 17-15A and B).Invasive Breast CarcinomaInvasive breast cancers have been described as lobular or duc-tal in origin.128-131 Early classifications used the term lobular to describe invasive cancers that were associated with LCIS, whereas all other invasive cancers were referred to as ductal. Current histologic classifications recognize special types of breast cancers (10% of total cases), which are defined by spe-cific histologic features. To qualify as a special-type cancer, at least 90% of the cancer must contain the defining histologic features. About 80% of invasive breast cancers are described as invasive ductal carcinoma of no special type (NST). These can-cers generally have a worse prognosis than special-type cancers. Foote and Stewart originally proposed the following classifica-tion for invasive breast cancer130:1. Paget’s disease of the nipple2. Invasive ductal
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have a worse prognosis than special-type cancers. Foote and Stewart originally proposed the following classifica-tion for invasive breast cancer130:1. Paget’s disease of the nipple2. Invasive ductal carcinoma—Adenocarcinoma with produc-tive fibrosis (scirrhous, simplex, NST), 80%3. Medullary carcinoma, 4%4. Mucinous (colloid) carcinoma, 2%5. Papillary carcinoma, 2%6. Tubular carcinoma, 2%7. Invasive lobular carcinoma, 10%8. Rare cancers (adenoid cystic, squamous cell, apocrine)Paget’s disease of the nipple was described in 1874. It fre-quently presents as a chronic, eczematous eruption of the nipple, which may be subtle but may progress to an ulcerated, weeping lesion. Paget’s disease usually is associated with extensive DCIS and may be associated with an invasive cancer. A palpable mass may or may not be present. A nipple biopsy specimen will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer
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Surgery_Schwartz. have a worse prognosis than special-type cancers. Foote and Stewart originally proposed the following classifica-tion for invasive breast cancer130:1. Paget’s disease of the nipple2. Invasive ductal carcinoma—Adenocarcinoma with produc-tive fibrosis (scirrhous, simplex, NST), 80%3. Medullary carcinoma, 4%4. Mucinous (colloid) carcinoma, 2%5. Papillary carcinoma, 2%6. Tubular carcinoma, 2%7. Invasive lobular carcinoma, 10%8. Rare cancers (adenoid cystic, squamous cell, apocrine)Paget’s disease of the nipple was described in 1874. It fre-quently presents as a chronic, eczematous eruption of the nipple, which may be subtle but may progress to an ulcerated, weeping lesion. Paget’s disease usually is associated with extensive DCIS and may be associated with an invasive cancer. A palpable mass may or may not be present. A nipple biopsy specimen will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer
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or may not be present. A nipple biopsy specimen will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium. Paget’s disease may be confused with superficial spreading melanoma. Differ-entiation from pagetoid intraepithelial melanoma is based on the presence of S-100 antigen immunostaining in melanoma and carcinoembryonic antigen immunostaining in Paget’s disease. Surgical therapy for Paget’s disease may involve lumpectomy or mastectomy, depending on the extent of involvement of the nipple-areolar complex and the presence of DCIS or invasive cancer in the underlying breast parenchyma.Invasive ductal carcinoma of the breast with productive fibrosis (scirrhous, simplex, NST) accounts for 80% of breast cancers and presents with macroscopic or microscopic axillary lymph node metastases in up to 25% of
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Surgery_Schwartz. or may not be present. A nipple biopsy specimen will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget cells) in the rete pegs of the epithelium. Paget’s disease may be confused with superficial spreading melanoma. Differ-entiation from pagetoid intraepithelial melanoma is based on the presence of S-100 antigen immunostaining in melanoma and carcinoembryonic antigen immunostaining in Paget’s disease. Surgical therapy for Paget’s disease may involve lumpectomy or mastectomy, depending on the extent of involvement of the nipple-areolar complex and the presence of DCIS or invasive cancer in the underlying breast parenchyma.Invasive ductal carcinoma of the breast with productive fibrosis (scirrhous, simplex, NST) accounts for 80% of breast cancers and presents with macroscopic or microscopic axillary lymph node metastases in up to 25% of
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of the breast with productive fibrosis (scirrhous, simplex, NST) accounts for 80% of breast cancers and presents with macroscopic or microscopic axillary lymph node metastases in up to 25% of screen-detected cases and up to 60% of symptomatic cases. This cancer occurs most frequently in perimenopausal or postmenopausal women in the fifth to sixth decades of life as a solitary, firm mass. It has poorly defined margins, and its cut surfaces show a central stellate con-figuration with chalky white or yellow streaks extending into surrounding breast tissues. The cancer cells often are arranged in small clusters, and there is a broad spectrum of histologic types with variable cellular and nuclear grades (Fig. 17-16A and B). In a large patient series from the SEER database, 75% of ductal cancers showed estrogen receptor expression.133Medullary carcinoma is a special-type breast cancer; it accounts for 4% of all invasive breast cancers and is a fre-quent phenotype of BRCA1 hereditary breast
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Surgery_Schwartz. of the breast with productive fibrosis (scirrhous, simplex, NST) accounts for 80% of breast cancers and presents with macroscopic or microscopic axillary lymph node metastases in up to 25% of screen-detected cases and up to 60% of symptomatic cases. This cancer occurs most frequently in perimenopausal or postmenopausal women in the fifth to sixth decades of life as a solitary, firm mass. It has poorly defined margins, and its cut surfaces show a central stellate con-figuration with chalky white or yellow streaks extending into surrounding breast tissues. The cancer cells often are arranged in small clusters, and there is a broad spectrum of histologic types with variable cellular and nuclear grades (Fig. 17-16A and B). In a large patient series from the SEER database, 75% of ductal cancers showed estrogen receptor expression.133Medullary carcinoma is a special-type breast cancer; it accounts for 4% of all invasive breast cancers and is a fre-quent phenotype of BRCA1 hereditary breast
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showed estrogen receptor expression.133Medullary carcinoma is a special-type breast cancer; it accounts for 4% of all invasive breast cancers and is a fre-quent phenotype of BRCA1 hereditary breast cancer. Grossly, the cancer is soft and hemorrhagic. A rapid increase in size may occur secondary to necrosis and hemorrhage. On physi-cal examination, it is bulky and often positioned deep within the breast. Bilaterality is reported in 20% of cases. Medullary carcinoma is characterized microscopically by: (a) a dense lym-phoreticular infiltrate composed predominantly of lymphocytes and plasma cells; (b) large pleomorphic nuclei that are poorly ABFigure 17-15. Ductal carcinoma in situ (DCIS). A. Craniocau-dal mammographic view shows a poorly defined mass containing microcalcifications. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.) B. Histopathologic preparation of the sur-gical specimen confirms DCIS with
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Surgery_Schwartz. showed estrogen receptor expression.133Medullary carcinoma is a special-type breast cancer; it accounts for 4% of all invasive breast cancers and is a fre-quent phenotype of BRCA1 hereditary breast cancer. Grossly, the cancer is soft and hemorrhagic. A rapid increase in size may occur secondary to necrosis and hemorrhage. On physi-cal examination, it is bulky and often positioned deep within the breast. Bilaterality is reported in 20% of cases. Medullary carcinoma is characterized microscopically by: (a) a dense lym-phoreticular infiltrate composed predominantly of lymphocytes and plasma cells; (b) large pleomorphic nuclei that are poorly ABFigure 17-15. Ductal carcinoma in situ (DCIS). A. Craniocau-dal mammographic view shows a poorly defined mass containing microcalcifications. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.) B. Histopathologic preparation of the sur-gical specimen confirms DCIS with
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permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.) B. Histopathologic preparation of the sur-gical specimen confirms DCIS with necrosis (100x). (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 56501/03/19 5:04 PM 566SPECIFIC CONSIDERATIONSPART IIABFigure 17-16. Invasive ductal carcinoma with productive fibrosis (scirrhous, simplex, no special type) A. 100x. B. 200x. (Used with permis-sion from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Figure 17-17. Lobular carcinoma (100×). Uniform, relatively small lobular carcinoma cells are seen arranged in a single-file orientation (“Indian file”). (Used with permission from Dr. Sindhu Menon,
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Surgery_Schwartz. permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.) B. Histopathologic preparation of the sur-gical specimen confirms DCIS with necrosis (100x). (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 56501/03/19 5:04 PM 566SPECIFIC CONSIDERATIONSPART IIABFigure 17-16. Invasive ductal carcinoma with productive fibrosis (scirrhous, simplex, no special type) A. 100x. B. 200x. (Used with permis-sion from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Figure 17-17. Lobular carcinoma (100×). Uniform, relatively small lobular carcinoma cells are seen arranged in a single-file orientation (“Indian file”). (Used with permission from Dr. Sindhu Menon,
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17-17. Lobular carcinoma (100×). Uniform, relatively small lobular carcinoma cells are seen arranged in a single-file orientation (“Indian file”). (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)differentiated and show active mitosis; and (c) a sheet-like growth pattern with minimal or absent ductal or alveolar dif-ferentiation. Approximately 50% of these cancers are associated with DCIS, which characteristically is present at the periphery of the cancer, and <10% demonstrate hormone receptors. In rare circumstances, mesenchymal metaplasia or anaplasia is noted. Because of the intense lymphocyte response associated with the cancer, benign or hyperplastic enlargement of the lymph nodes of the axilla may contribute to erroneous clinical staging. Women with this cancer have a better 5-year survival rate than those with NST or invasive lobular
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Surgery_Schwartz. 17-17. Lobular carcinoma (100×). Uniform, relatively small lobular carcinoma cells are seen arranged in a single-file orientation (“Indian file”). (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)differentiated and show active mitosis; and (c) a sheet-like growth pattern with minimal or absent ductal or alveolar dif-ferentiation. Approximately 50% of these cancers are associated with DCIS, which characteristically is present at the periphery of the cancer, and <10% demonstrate hormone receptors. In rare circumstances, mesenchymal metaplasia or anaplasia is noted. Because of the intense lymphocyte response associated with the cancer, benign or hyperplastic enlargement of the lymph nodes of the axilla may contribute to erroneous clinical staging. Women with this cancer have a better 5-year survival rate than those with NST or invasive lobular
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enlargement of the lymph nodes of the axilla may contribute to erroneous clinical staging. Women with this cancer have a better 5-year survival rate than those with NST or invasive lobular carcinoma.Mucinous carcinoma (colloid carcinoma), another spe-cial-type breast cancer, accounts for 2% of all invasive breast cancers and typically presents in the older population as a bulky tumor. This cancer is defined by extracellular pools of mucin, which surround aggregates of low-grade cancer cells. The cut surface of this cancer is glistening and gelatinous in quality. Fibrosis is variable, and when abundant it imparts a firm consis-tency to the cancer. Over 90% of mucinous carcinomas display hormone receptors.133 Lymph node metastases occur in 33% of cases, and 5and 10-year survival rates are 73% and 59%, respectively. Because of the mucinous component, cancer cells may not be evident in all microscopic sections, and analysis of multiple sections is essential to confirm the diagnosis of a
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Surgery_Schwartz. enlargement of the lymph nodes of the axilla may contribute to erroneous clinical staging. Women with this cancer have a better 5-year survival rate than those with NST or invasive lobular carcinoma.Mucinous carcinoma (colloid carcinoma), another spe-cial-type breast cancer, accounts for 2% of all invasive breast cancers and typically presents in the older population as a bulky tumor. This cancer is defined by extracellular pools of mucin, which surround aggregates of low-grade cancer cells. The cut surface of this cancer is glistening and gelatinous in quality. Fibrosis is variable, and when abundant it imparts a firm consis-tency to the cancer. Over 90% of mucinous carcinomas display hormone receptors.133 Lymph node metastases occur in 33% of cases, and 5and 10-year survival rates are 73% and 59%, respectively. Because of the mucinous component, cancer cells may not be evident in all microscopic sections, and analysis of multiple sections is essential to confirm the diagnosis of a
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73% and 59%, respectively. Because of the mucinous component, cancer cells may not be evident in all microscopic sections, and analysis of multiple sections is essential to confirm the diagnosis of a mucinous carcinoma.Papillary carcinoma is a special-type cancer of the breast that accounts for 2% of all invasive breast cancers. It generally presents in the seventh decade of life and occurs in a dispropor-tionate number of nonwhite women. Typically, papillary car-cinomas are small and rarely attain a size of 3 cm in diameter. These cancers are defined by papillae with fibrovascular stalks and multilayered epithelium. In a large series from the SEER database 87% of papillary cancers have been reported to express estrogen receptor.133 McDivitt and colleagues noted that these tumors showed a low frequency of axillary lymph node metas-tases and had 5and 10-year survival rates similar to those for mucinous and tubular carcinoma.134Tubular carcinoma is another special-type breast cancer and
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Surgery_Schwartz. 73% and 59%, respectively. Because of the mucinous component, cancer cells may not be evident in all microscopic sections, and analysis of multiple sections is essential to confirm the diagnosis of a mucinous carcinoma.Papillary carcinoma is a special-type cancer of the breast that accounts for 2% of all invasive breast cancers. It generally presents in the seventh decade of life and occurs in a dispropor-tionate number of nonwhite women. Typically, papillary car-cinomas are small and rarely attain a size of 3 cm in diameter. These cancers are defined by papillae with fibrovascular stalks and multilayered epithelium. In a large series from the SEER database 87% of papillary cancers have been reported to express estrogen receptor.133 McDivitt and colleagues noted that these tumors showed a low frequency of axillary lymph node metas-tases and had 5and 10-year survival rates similar to those for mucinous and tubular carcinoma.134Tubular carcinoma is another special-type breast cancer and
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low frequency of axillary lymph node metas-tases and had 5and 10-year survival rates similar to those for mucinous and tubular carcinoma.134Tubular carcinoma is another special-type breast cancer and accounts for 2% of all invasive breast cancers. It is reported in as many as 20% of women whose cancers are diagnosed by mammographic screening and usually is diagnosed in the perimenopausal or early menopausal periods. Under low-power magnification, a haphazard array of small, randomly arranged tubular elements is seen. In a large SEER database 94% of tubular cancers were reported to express estrogen receptor.133 Approximately 10% of women with tubular carcinoma or with invasive cribriform carcinoma, a special-type cancer closely related to tubular carcinoma, will develop axillary lymph node metastases. However, the presence of metastatic disease in one or two axillary lymph nodes does not adversely affect survival. Distant metastases are rare in tubular carcinoma and invasive cribriform
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Surgery_Schwartz. low frequency of axillary lymph node metas-tases and had 5and 10-year survival rates similar to those for mucinous and tubular carcinoma.134Tubular carcinoma is another special-type breast cancer and accounts for 2% of all invasive breast cancers. It is reported in as many as 20% of women whose cancers are diagnosed by mammographic screening and usually is diagnosed in the perimenopausal or early menopausal periods. Under low-power magnification, a haphazard array of small, randomly arranged tubular elements is seen. In a large SEER database 94% of tubular cancers were reported to express estrogen receptor.133 Approximately 10% of women with tubular carcinoma or with invasive cribriform carcinoma, a special-type cancer closely related to tubular carcinoma, will develop axillary lymph node metastases. However, the presence of metastatic disease in one or two axillary lymph nodes does not adversely affect survival. Distant metastases are rare in tubular carcinoma and invasive cribriform
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metastases. However, the presence of metastatic disease in one or two axillary lymph nodes does not adversely affect survival. Distant metastases are rare in tubular carcinoma and invasive cribriform carcinoma. Long-term survival approaches 100%.Invasive lobular carcinoma accounts for 10% of breast cancers. The histopathologic features of this cancer include small cells with rounded nuclei, inconspicuous nucleoli, and scant cytoplasm (Fig. 17-17). Special stains may confirm the Brunicardi_Ch17_p0541-p0612.indd 56601/03/19 5:04 PM 567THE BREASTCHAPTER 17presence of intracytoplasmic mucin, which may displace the nucleus (signet-ring cell carcinoma). At presentation, invasive lobular carcinoma varies from clinically inapparent carcinomas to those that replace the entire breast with a poorly defined mass. It is frequently multifocal, multicentric, and bilateral. Because of its insidious growth pattern and subtle mammographic fea-tures, invasive lobular carcinoma may be difficult to
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Surgery_Schwartz. metastases. However, the presence of metastatic disease in one or two axillary lymph nodes does not adversely affect survival. Distant metastases are rare in tubular carcinoma and invasive cribriform carcinoma. Long-term survival approaches 100%.Invasive lobular carcinoma accounts for 10% of breast cancers. The histopathologic features of this cancer include small cells with rounded nuclei, inconspicuous nucleoli, and scant cytoplasm (Fig. 17-17). Special stains may confirm the Brunicardi_Ch17_p0541-p0612.indd 56601/03/19 5:04 PM 567THE BREASTCHAPTER 17presence of intracytoplasmic mucin, which may displace the nucleus (signet-ring cell carcinoma). At presentation, invasive lobular carcinoma varies from clinically inapparent carcinomas to those that replace the entire breast with a poorly defined mass. It is frequently multifocal, multicentric, and bilateral. Because of its insidious growth pattern and subtle mammographic fea-tures, invasive lobular carcinoma may be difficult to
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defined mass. It is frequently multifocal, multicentric, and bilateral. Because of its insidious growth pattern and subtle mammographic fea-tures, invasive lobular carcinoma may be difficult to detect. Over 90% of lobular cancers express estrogen receptor.133DIAGNOSIS OF BREAST CANCERIn ∼30% of cases, the woman discovers a lump in her breast. Other less frequent presenting signs and symptoms of breast cancer include: (a) breast enlargement or asymmetry; (b) nipple changes, retraction, or discharge; (c) ulceration or erythema of the skin of the breast; (d) an axillary mass; and (e) musculoskel-etal discomfort. However, up to 50% of women presenting with breast complaints have no physical signs of breast pathology. Breast pain usually is associated with benign disease.Misdiagnosed breast cancer accounts for the greatest num-ber of malpractice claims for errors in diagnosis and for the largest number of paid claims. Litigation often involves younger women, whose physical examination and
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Surgery_Schwartz. defined mass. It is frequently multifocal, multicentric, and bilateral. Because of its insidious growth pattern and subtle mammographic fea-tures, invasive lobular carcinoma may be difficult to detect. Over 90% of lobular cancers express estrogen receptor.133DIAGNOSIS OF BREAST CANCERIn ∼30% of cases, the woman discovers a lump in her breast. Other less frequent presenting signs and symptoms of breast cancer include: (a) breast enlargement or asymmetry; (b) nipple changes, retraction, or discharge; (c) ulceration or erythema of the skin of the breast; (d) an axillary mass; and (e) musculoskel-etal discomfort. However, up to 50% of women presenting with breast complaints have no physical signs of breast pathology. Breast pain usually is associated with benign disease.Misdiagnosed breast cancer accounts for the greatest num-ber of malpractice claims for errors in diagnosis and for the largest number of paid claims. Litigation often involves younger women, whose physical examination and
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accounts for the greatest num-ber of malpractice claims for errors in diagnosis and for the largest number of paid claims. Litigation often involves younger women, whose physical examination and mammogram may be misleading. If a young woman (≤45 years) presents with a palpable breast mass and equivocal mammographic findings, ultrasound examination and biopsy are used to avoid a delay in diagnosis.ExaminationInspection. The clinician inspects the woman’s breast with her arms by her side (Fig. 17-18A), with her arms straight up in the air (Fig. 17-18B), and with her hands on her hips (with and without pectoral muscle contraction).135,136 Symmetry, size, and shape of the breast are recorded, as well as any evidence of edema (peau d’orange), nipple or skin retraction, or erythema. With the arms extended forward and in a sitting position, the woman leans forward to accentuate any skin retraction.Figure 17-18. Examination of the breast. A. Inspection of the breast with arms at sides. B.
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Surgery_Schwartz. accounts for the greatest num-ber of malpractice claims for errors in diagnosis and for the largest number of paid claims. Litigation often involves younger women, whose physical examination and mammogram may be misleading. If a young woman (≤45 years) presents with a palpable breast mass and equivocal mammographic findings, ultrasound examination and biopsy are used to avoid a delay in diagnosis.ExaminationInspection. The clinician inspects the woman’s breast with her arms by her side (Fig. 17-18A), with her arms straight up in the air (Fig. 17-18B), and with her hands on her hips (with and without pectoral muscle contraction).135,136 Symmetry, size, and shape of the breast are recorded, as well as any evidence of edema (peau d’orange), nipple or skin retraction, or erythema. With the arms extended forward and in a sitting position, the woman leans forward to accentuate any skin retraction.Figure 17-18. Examination of the breast. A. Inspection of the breast with arms at sides. B.
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arms extended forward and in a sitting position, the woman leans forward to accentuate any skin retraction.Figure 17-18. Examination of the breast. A. Inspection of the breast with arms at sides. B. Inspection of the breast with arms raised. C. Palpation of the breast with the patient supine. D. Palpa-tion of the axilla.Palpation. As part of the physical examination, the breast is carefully palpated. With the patient in the supine position (see Fig. 17-18C) the clinician gently palpates the breasts, making certain to examine all quadrants of the breast from the sternum laterally to the latissimus dorsi muscle and from the clavicle inferiorly to the upper rectus sheath. The examination is per-formed with the palmar aspects of the fingers, avoiding a grasp-ing or pinching motion. The breast may be cupped or molded in the examiner’s hands to check for retraction. A systematic search for lymphadenopathy then is performed. Figure 17-18D shows the position of the patient for examination of
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Surgery_Schwartz. arms extended forward and in a sitting position, the woman leans forward to accentuate any skin retraction.Figure 17-18. Examination of the breast. A. Inspection of the breast with arms at sides. B. Inspection of the breast with arms raised. C. Palpation of the breast with the patient supine. D. Palpa-tion of the axilla.Palpation. As part of the physical examination, the breast is carefully palpated. With the patient in the supine position (see Fig. 17-18C) the clinician gently palpates the breasts, making certain to examine all quadrants of the breast from the sternum laterally to the latissimus dorsi muscle and from the clavicle inferiorly to the upper rectus sheath. The examination is per-formed with the palmar aspects of the fingers, avoiding a grasp-ing or pinching motion. The breast may be cupped or molded in the examiner’s hands to check for retraction. A systematic search for lymphadenopathy then is performed. Figure 17-18D shows the position of the patient for examination of
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may be cupped or molded in the examiner’s hands to check for retraction. A systematic search for lymphadenopathy then is performed. Figure 17-18D shows the position of the patient for examination of the axilla. By supporting the upper arm and elbow, the examiner stabi-lizes the shoulder girdle. Using gentle palpation, the clinician assesses all three levels of possible axillary lymphadenopathy. Careful palpation of supraclavicular and parasternal sites also is performed. A diagram of the chest and contiguous lymph node sites is useful for recording location, size, consistency, shape, mobility, fixation, and other characteristics of any palpable breast mass or lymphadenopathy (Fig. 17-19).Imaging TechniquesMammography. Mammography has been used in North Amer-ica since the 1960s, and the techniques used continue to be mod-ified and improved to enhance image quality.137-140 Conventional mammography delivers a radiation dose of 0.1 cGy per study. By comparison, chest radiography delivers
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Surgery_Schwartz. may be cupped or molded in the examiner’s hands to check for retraction. A systematic search for lymphadenopathy then is performed. Figure 17-18D shows the position of the patient for examination of the axilla. By supporting the upper arm and elbow, the examiner stabi-lizes the shoulder girdle. Using gentle palpation, the clinician assesses all three levels of possible axillary lymphadenopathy. Careful palpation of supraclavicular and parasternal sites also is performed. A diagram of the chest and contiguous lymph node sites is useful for recording location, size, consistency, shape, mobility, fixation, and other characteristics of any palpable breast mass or lymphadenopathy (Fig. 17-19).Imaging TechniquesMammography. Mammography has been used in North Amer-ica since the 1960s, and the techniques used continue to be mod-ified and improved to enhance image quality.137-140 Conventional mammography delivers a radiation dose of 0.1 cGy per study. By comparison, chest radiography delivers
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used continue to be mod-ified and improved to enhance image quality.137-140 Conventional mammography delivers a radiation dose of 0.1 cGy per study. By comparison, chest radiography delivers 25% of this dose. However, there is no increased breast cancer risk associated with the radiation dose delivered with screening mammography. Screening mammography is used to detect unexpected breast cancer in asymptomatic women. In this regard, it supplements history taking and physical examination. With screening mam-mography, two views of the breast are obtained: the craniocau-dal (CC) view (Fig. 17-20A,B) and the mediolateral oblique (MLO) view (Fig. 17-20C,D). The MLO view images the great-est volume of breast tissue, including the upper outer quadrant and the axillary tail of Spence. Compared with the MLO view, the CC view provides better visualization of the medial aspect of the breast and permits greater breast compression. Diagnos-tic mammography is used to evaluate women with abnormal
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Surgery_Schwartz. used continue to be mod-ified and improved to enhance image quality.137-140 Conventional mammography delivers a radiation dose of 0.1 cGy per study. By comparison, chest radiography delivers 25% of this dose. However, there is no increased breast cancer risk associated with the radiation dose delivered with screening mammography. Screening mammography is used to detect unexpected breast cancer in asymptomatic women. In this regard, it supplements history taking and physical examination. With screening mam-mography, two views of the breast are obtained: the craniocau-dal (CC) view (Fig. 17-20A,B) and the mediolateral oblique (MLO) view (Fig. 17-20C,D). The MLO view images the great-est volume of breast tissue, including the upper outer quadrant and the axillary tail of Spence. Compared with the MLO view, the CC view provides better visualization of the medial aspect of the breast and permits greater breast compression. Diagnos-tic mammography is used to evaluate women with abnormal
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with the MLO view, the CC view provides better visualization of the medial aspect of the breast and permits greater breast compression. Diagnos-tic mammography is used to evaluate women with abnormal Figure 17-19. A breast examination record. Brunicardi_Ch17_p0541-p0612.indd 56701/03/19 5:04 PM 568SPECIFIC CONSIDERATIONSPART IIABCDFigure 17-20. A-D. Mammogram of a premenopausal breast with a dense fibroglandular pattern. E-H. Mammogram of a postmenopausal breast with a sparse fibroglandular pattern. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 56801/03/19 5:04 PM 569THE BREASTCHAPTER 17EFGHFigure 17-20. (Continued)findings such as a breast mass or nipple discharge. In addition to the MLO and CC views, a diagnostic examination may use views that better define the nature of any abnormalities, such as the 90° lateral and spot compression views. The 90° lateral
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Surgery_Schwartz. with the MLO view, the CC view provides better visualization of the medial aspect of the breast and permits greater breast compression. Diagnos-tic mammography is used to evaluate women with abnormal Figure 17-19. A breast examination record. Brunicardi_Ch17_p0541-p0612.indd 56701/03/19 5:04 PM 568SPECIFIC CONSIDERATIONSPART IIABCDFigure 17-20. A-D. Mammogram of a premenopausal breast with a dense fibroglandular pattern. E-H. Mammogram of a postmenopausal breast with a sparse fibroglandular pattern. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 56801/03/19 5:04 PM 569THE BREASTCHAPTER 17EFGHFigure 17-20. (Continued)findings such as a breast mass or nipple discharge. In addition to the MLO and CC views, a diagnostic examination may use views that better define the nature of any abnormalities, such as the 90° lateral and spot compression views. The 90° lateral
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In addition to the MLO and CC views, a diagnostic examination may use views that better define the nature of any abnormalities, such as the 90° lateral and spot compression views. The 90° lateral view is used along with the CC view to triangulate the exact location of an abnormality. Spot compression may be done in any pro-jection by using a small compression device, which is placed directly over a mammographic abnormality that is obscured by overlying tissues (Fig. 17-21C). The compression device mini-mizes motion artifact, improves definition, separates overlying tissues, and decreases the radiation dose needed to penetrate the breast. Magnification techniques (×1.5) often are combined with spot compression to better resolve calcifications and the margins of masses. Mammography also is used to guide inter-ventional procedures, including needle localization and needle biopsy.Brunicardi_Ch17_p0541-p0612.indd 56901/03/19 5:04 PM 570SPECIFIC CONSIDERATIONSPART IIABCFigure
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Surgery_Schwartz. In addition to the MLO and CC views, a diagnostic examination may use views that better define the nature of any abnormalities, such as the 90° lateral and spot compression views. The 90° lateral view is used along with the CC view to triangulate the exact location of an abnormality. Spot compression may be done in any pro-jection by using a small compression device, which is placed directly over a mammographic abnormality that is obscured by overlying tissues (Fig. 17-21C). The compression device mini-mizes motion artifact, improves definition, separates overlying tissues, and decreases the radiation dose needed to penetrate the breast. Magnification techniques (×1.5) often are combined with spot compression to better resolve calcifications and the margins of masses. Mammography also is used to guide inter-ventional procedures, including needle localization and needle biopsy.Brunicardi_Ch17_p0541-p0612.indd 56901/03/19 5:04 PM 570SPECIFIC CONSIDERATIONSPART IIABCFigure
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also is used to guide inter-ventional procedures, including needle localization and needle biopsy.Brunicardi_Ch17_p0541-p0612.indd 56901/03/19 5:04 PM 570SPECIFIC CONSIDERATIONSPART IIABCFigure 17-21. Mammogram revealing a small, spiculated mass in the right breast A. A small, spiculated mass is seen in the right breast with skin tethering (CC view). B. Mass seen on oblique view of the right breast. C. Spot compression mammography view of the cancer seen in A and B. The spiculated margins of the cancer are accentuated by compression. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Specific mammographic features that suggest a diagnosis of breast cancer include a solid mass with or without stellate features, asymmetric thickening of breast tissues, and clustered microcalcifications. The presence of fine, stippled calcium in and around a suspicious lesion is suggestive of breast cancer and occurs in
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Surgery_Schwartz. also is used to guide inter-ventional procedures, including needle localization and needle biopsy.Brunicardi_Ch17_p0541-p0612.indd 56901/03/19 5:04 PM 570SPECIFIC CONSIDERATIONSPART IIABCFigure 17-21. Mammogram revealing a small, spiculated mass in the right breast A. A small, spiculated mass is seen in the right breast with skin tethering (CC view). B. Mass seen on oblique view of the right breast. C. Spot compression mammography view of the cancer seen in A and B. The spiculated margins of the cancer are accentuated by compression. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Specific mammographic features that suggest a diagnosis of breast cancer include a solid mass with or without stellate features, asymmetric thickening of breast tissues, and clustered microcalcifications. The presence of fine, stippled calcium in and around a suspicious lesion is suggestive of breast cancer and occurs in
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asymmetric thickening of breast tissues, and clustered microcalcifications. The presence of fine, stippled calcium in and around a suspicious lesion is suggestive of breast cancer and occurs in as many as 50% of nonpalpable cancers. These microcalcifications are an especially important sign of cancer in younger women, in whom it may be the only mammographic abnormality. The clinical impetus for screening mammogra-phy came from the Health Insurance Plan study and the Breast Cancer Detection Demonstration Project, which demonstrated a 33% reduction in mortality for women after72 screening mam-mography. Mammography was more accurate than clinical examination for the detection of early breast cancers, providing a true-positive rate of 90%. Only 20% of women with nonpal-pable cancers had axillary lymph node metastases, compared with 50% of women with palpable cancers.141 Current guide-lines of the National Comprehensive Cancer Network suggest that normal-risk women ≥20 years of age should
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Surgery_Schwartz. asymmetric thickening of breast tissues, and clustered microcalcifications. The presence of fine, stippled calcium in and around a suspicious lesion is suggestive of breast cancer and occurs in as many as 50% of nonpalpable cancers. These microcalcifications are an especially important sign of cancer in younger women, in whom it may be the only mammographic abnormality. The clinical impetus for screening mammogra-phy came from the Health Insurance Plan study and the Breast Cancer Detection Demonstration Project, which demonstrated a 33% reduction in mortality for women after72 screening mam-mography. Mammography was more accurate than clinical examination for the detection of early breast cancers, providing a true-positive rate of 90%. Only 20% of women with nonpal-pable cancers had axillary lymph node metastases, compared with 50% of women with palpable cancers.141 Current guide-lines of the National Comprehensive Cancer Network suggest that normal-risk women ≥20 years of age should
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lymph node metastases, compared with 50% of women with palpable cancers.141 Current guide-lines of the National Comprehensive Cancer Network suggest that normal-risk women ≥20 years of age should have a breast examination at least every 3 years. Starting at age 40 years, breast examinations should be performed yearly, and a yearly mammogram should be taken.142 Screening mammography in women ≥50 years of age has been noted to reduce breast cancer mortality by 20% to 25%.72,79 With the increased discussion about the potential harms associated with breast screening, the United Kingdom recently established an independent expert panel to review the published literature and estimate the ben-efits and harms associated with its national screening program for women age >50 years. The panel estimated that in women invited to screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite this overdiagno-sis, the panel concluded that breast screening programs
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Surgery_Schwartz. lymph node metastases, compared with 50% of women with palpable cancers.141 Current guide-lines of the National Comprehensive Cancer Network suggest that normal-risk women ≥20 years of age should have a breast examination at least every 3 years. Starting at age 40 years, breast examinations should be performed yearly, and a yearly mammogram should be taken.142 Screening mammography in women ≥50 years of age has been noted to reduce breast cancer mortality by 20% to 25%.72,79 With the increased discussion about the potential harms associated with breast screening, the United Kingdom recently established an independent expert panel to review the published literature and estimate the ben-efits and harms associated with its national screening program for women age >50 years. The panel estimated that in women invited to screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite this overdiagno-sis, the panel concluded that breast screening programs
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that in women invited to screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite this overdiagno-sis, the panel concluded that breast screening programs confer significant benefit and should continue. The use of screening mammography in women <50 years of age is more controversial for previously noted reasons: (a) reduced sensitivity, (b) reduced specificity, and (c) lower incidence of breast cancer. Because of the combination of these three reasons, targeting mammography screening to women <50 years of age, who are at higher risk of breast cancer, improves the balance of risks and benefits and is the approach some health care systems have taken. There are now a number of risk assessment models—as described earlier in this chapter—that can be used to estimate a younger woman’s risk of developing breast cancer and that help assess the risks and benefits of regular screening.Screen film mammography has replaced xeromam-mography because it
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Surgery_Schwartz. that in women invited to screening, about 11% of the cancers diagnosed in their lifetime constitute overdiagnosis. Despite this overdiagno-sis, the panel concluded that breast screening programs confer significant benefit and should continue. The use of screening mammography in women <50 years of age is more controversial for previously noted reasons: (a) reduced sensitivity, (b) reduced specificity, and (c) lower incidence of breast cancer. Because of the combination of these three reasons, targeting mammography screening to women <50 years of age, who are at higher risk of breast cancer, improves the balance of risks and benefits and is the approach some health care systems have taken. There are now a number of risk assessment models—as described earlier in this chapter—that can be used to estimate a younger woman’s risk of developing breast cancer and that help assess the risks and benefits of regular screening.Screen film mammography has replaced xeromam-mography because it
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used to estimate a younger woman’s risk of developing breast cancer and that help assess the risks and benefits of regular screening.Screen film mammography has replaced xeromam-mography because it requires a lower dose of radiation and provides similar image quality. Digital mammography was developed to allow the observer to manipulate the degree of contrast in the image. This is especially useful in women with dense breasts and women <50 years of age. Recently, investigators directly compared digital vs. screen film mam-mography in a prospective (DMIST) trial that enrolled over 42,000 women.143 The investigators found that digital and screen film mammography had similar accuracy; however, digital mammography was more accurate in women <50 years of age, women with mammographically dense breasts, and premenopausal or perimenopausal women. The use of digital breast tomosynthesis with 3D images has been introduced as an alternative to standard 2D mammography imaging that is limited by
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Surgery_Schwartz. used to estimate a younger woman’s risk of developing breast cancer and that help assess the risks and benefits of regular screening.Screen film mammography has replaced xeromam-mography because it requires a lower dose of radiation and provides similar image quality. Digital mammography was developed to allow the observer to manipulate the degree of contrast in the image. This is especially useful in women with dense breasts and women <50 years of age. Recently, investigators directly compared digital vs. screen film mam-mography in a prospective (DMIST) trial that enrolled over 42,000 women.143 The investigators found that digital and screen film mammography had similar accuracy; however, digital mammography was more accurate in women <50 years of age, women with mammographically dense breasts, and premenopausal or perimenopausal women. The use of digital breast tomosynthesis with 3D images has been introduced as an alternative to standard 2D mammography imaging that is limited by
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breasts, and premenopausal or perimenopausal women. The use of digital breast tomosynthesis with 3D images has been introduced as an alternative to standard 2D mammography imaging that is limited by superimposition of breast parenchyma and breast density.144,145 The STORM trial reported that in 7,292 women screened, 3D mammography had a higher cancer detection rate and fewer false-positive recalls than the standard 2D imaging.146,147 Randomized controlled trials are planned to fur-ther study tomosynthesis and its role in breast cancer screen-ing. Standard two-dimensional mammography has limitations, Brunicardi_Ch17_p0541-p0612.indd 57001/03/19 5:04 PM 571THE BREASTCHAPTER 17such as the parenchymal density or superimposition of breast tissue, which obscures cancers or causes normal structures to appear suspicious reducing the sensitivity of mammography and increasing the false-positive rates. Digital breast tomo-synthesis is a technology developed to assist with overcom-ing these
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Surgery_Schwartz. breasts, and premenopausal or perimenopausal women. The use of digital breast tomosynthesis with 3D images has been introduced as an alternative to standard 2D mammography imaging that is limited by superimposition of breast parenchyma and breast density.144,145 The STORM trial reported that in 7,292 women screened, 3D mammography had a higher cancer detection rate and fewer false-positive recalls than the standard 2D imaging.146,147 Randomized controlled trials are planned to fur-ther study tomosynthesis and its role in breast cancer screen-ing. Standard two-dimensional mammography has limitations, Brunicardi_Ch17_p0541-p0612.indd 57001/03/19 5:04 PM 571THE BREASTCHAPTER 17such as the parenchymal density or superimposition of breast tissue, which obscures cancers or causes normal structures to appear suspicious reducing the sensitivity of mammography and increasing the false-positive rates. Digital breast tomo-synthesis is a technology developed to assist with overcom-ing these
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to appear suspicious reducing the sensitivity of mammography and increasing the false-positive rates. Digital breast tomo-synthesis is a technology developed to assist with overcom-ing these limitations. In digital breast tomosynthesis, multiple projection images are reconstructed to allow visual review of thin breast sections, each reconstructed slice as thin as 0.5 mm, which provides better characterization of noncalcified lesions. These multiple projection exposures are obtained by a digi-tal detector from a mammography X-ray source that moves through a limited arc angle while the breast is compressed. Then these projection image data sets are reconstructed using specific algorithms, which provide the clinical reader a series of images through the entire breast.148In 2011, tomosynthesis was approved by the U.S. Food and Drug Administration (FDA) to be used in combination with standard digital mammography for breast cancer screening. The total radiation dose when tomosynthesis is
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Surgery_Schwartz. to appear suspicious reducing the sensitivity of mammography and increasing the false-positive rates. Digital breast tomo-synthesis is a technology developed to assist with overcom-ing these limitations. In digital breast tomosynthesis, multiple projection images are reconstructed to allow visual review of thin breast sections, each reconstructed slice as thin as 0.5 mm, which provides better characterization of noncalcified lesions. These multiple projection exposures are obtained by a digi-tal detector from a mammography X-ray source that moves through a limited arc angle while the breast is compressed. Then these projection image data sets are reconstructed using specific algorithms, which provide the clinical reader a series of images through the entire breast.148In 2011, tomosynthesis was approved by the U.S. Food and Drug Administration (FDA) to be used in combination with standard digital mammography for breast cancer screening. The total radiation dose when tomosynthesis is
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was approved by the U.S. Food and Drug Administration (FDA) to be used in combination with standard digital mammography for breast cancer screening. The total radiation dose when tomosynthesis is added is about twice the current dose of digital mammography alone but remains below the limits set by the FDA.149The STORM-2 trial reported that synthetic 2D-3D mammography yields similar breast cancer detection as dual-acquisition 2D-3D mammography with the advantage of reduc-ing radiation exposure.150Contrast-enhanced digital mammography (CEDM) was also approved by the FDA in 2001, which utilizes an iodinated contrast material and modified digital mammography units for imaging.148 CEDM has been shown to be feasible and detects breast cancers at a rate similar to MRI, which has potential to offer an alternative to MRI.151 The advantages of CEDM over MRI are that the use of compression limits motion, there is decrease in cost, decrease in exam time, and there is an option for patients who
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Surgery_Schwartz. was approved by the U.S. Food and Drug Administration (FDA) to be used in combination with standard digital mammography for breast cancer screening. The total radiation dose when tomosynthesis is added is about twice the current dose of digital mammography alone but remains below the limits set by the FDA.149The STORM-2 trial reported that synthetic 2D-3D mammography yields similar breast cancer detection as dual-acquisition 2D-3D mammography with the advantage of reduc-ing radiation exposure.150Contrast-enhanced digital mammography (CEDM) was also approved by the FDA in 2001, which utilizes an iodinated contrast material and modified digital mammography units for imaging.148 CEDM has been shown to be feasible and detects breast cancers at a rate similar to MRI, which has potential to offer an alternative to MRI.151 The advantages of CEDM over MRI are that the use of compression limits motion, there is decrease in cost, decrease in exam time, and there is an option for patients who
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an alternative to MRI.151 The advantages of CEDM over MRI are that the use of compression limits motion, there is decrease in cost, decrease in exam time, and there is an option for patients who are unable to tolerate MRI or who due to vari-ous reasons cannot have MRI due to incompatibility, such as the presence of a pacemaker or tissue expanders.148,152Ductography. The primary indication for ductography is nipple discharge, particularly when the fluid contains blood. Radiopaque contrast media is injected into one or more of the major ducts, and mammography is performed. A duct is gen-tly enlarged with a dilator, and then a small, blunt cannula is inserted under sterile conditions into the nipple ampulla. With the patient in a supine position, 0.1 to 0.2 mL of dilute con-trast media is injected, and CC and MLO mammographic views are obtained without compression. Intraductal papillomas are seen as small filling defects surrounded by contrast media (Fig. 17-22). Cancers may appear as
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Surgery_Schwartz. an alternative to MRI.151 The advantages of CEDM over MRI are that the use of compression limits motion, there is decrease in cost, decrease in exam time, and there is an option for patients who are unable to tolerate MRI or who due to vari-ous reasons cannot have MRI due to incompatibility, such as the presence of a pacemaker or tissue expanders.148,152Ductography. The primary indication for ductography is nipple discharge, particularly when the fluid contains blood. Radiopaque contrast media is injected into one or more of the major ducts, and mammography is performed. A duct is gen-tly enlarged with a dilator, and then a small, blunt cannula is inserted under sterile conditions into the nipple ampulla. With the patient in a supine position, 0.1 to 0.2 mL of dilute con-trast media is injected, and CC and MLO mammographic views are obtained without compression. Intraductal papillomas are seen as small filling defects surrounded by contrast media (Fig. 17-22). Cancers may appear as
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injected, and CC and MLO mammographic views are obtained without compression. Intraductal papillomas are seen as small filling defects surrounded by contrast media (Fig. 17-22). Cancers may appear as irregular masses or as mul-tiple intraluminal filling defects.Ultrasonography. Second only to mammography in fre-quency of use for breast imaging, ultrasonography is an impor-tant method of resolving equivocal mammographic findings, defining cystic masses, and demonstrating the echogenic qual-ities of specific solid abnormalities. On ultrasound examina-tion, breast cysts are well circumscribed, with smooth margins and an echo-free center (Fig. 17-23). Benign breast masses usually show smooth contours, round or oval shapes, weak internal echoes, and well-defined anterior and posterior mar-gins (Fig. 17-24). Breast cancer characteristically has irregular walls (Fig. 17-25) but may have smooth margins with acous-tic enhancement. Ultrasonography is used to guide fine-needle aspiration biopsy,
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Surgery_Schwartz. injected, and CC and MLO mammographic views are obtained without compression. Intraductal papillomas are seen as small filling defects surrounded by contrast media (Fig. 17-22). Cancers may appear as irregular masses or as mul-tiple intraluminal filling defects.Ultrasonography. Second only to mammography in fre-quency of use for breast imaging, ultrasonography is an impor-tant method of resolving equivocal mammographic findings, defining cystic masses, and demonstrating the echogenic qual-ities of specific solid abnormalities. On ultrasound examina-tion, breast cysts are well circumscribed, with smooth margins and an echo-free center (Fig. 17-23). Benign breast masses usually show smooth contours, round or oval shapes, weak internal echoes, and well-defined anterior and posterior mar-gins (Fig. 17-24). Breast cancer characteristically has irregular walls (Fig. 17-25) but may have smooth margins with acous-tic enhancement. Ultrasonography is used to guide fine-needle aspiration biopsy,
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(Fig. 17-24). Breast cancer characteristically has irregular walls (Fig. 17-25) but may have smooth margins with acous-tic enhancement. Ultrasonography is used to guide fine-needle aspiration biopsy, core-needle biopsy, and needle localization ABFigure 17-22. Ductogram. Craniocaudal (A) and mediolateral oblique (B) mammographic views demonstrate a mass (arrows) posterior to the nipple and outlined by contrast, which also fills the proximal ductal structures. (Used with permission from B. Steinbach.)of breast lesions. Its findings are highly reproducible, and it has a high patient acceptance rate, but it does not reliably detect lesions that are ≤1 cm in diameter. Ultrasonography can also be utilized to image the regional lymph nodes in patients with breast cancer (Fig. 17-26). The sensitivity of examination for the status of axillary nodes ranges from 35% to 82% and specificity ranges from 73% to 97%. The features of a lymph node involved with cancer include cortical thickening,
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Surgery_Schwartz. (Fig. 17-24). Breast cancer characteristically has irregular walls (Fig. 17-25) but may have smooth margins with acous-tic enhancement. Ultrasonography is used to guide fine-needle aspiration biopsy, core-needle biopsy, and needle localization ABFigure 17-22. Ductogram. Craniocaudal (A) and mediolateral oblique (B) mammographic views demonstrate a mass (arrows) posterior to the nipple and outlined by contrast, which also fills the proximal ductal structures. (Used with permission from B. Steinbach.)of breast lesions. Its findings are highly reproducible, and it has a high patient acceptance rate, but it does not reliably detect lesions that are ≤1 cm in diameter. Ultrasonography can also be utilized to image the regional lymph nodes in patients with breast cancer (Fig. 17-26). The sensitivity of examination for the status of axillary nodes ranges from 35% to 82% and specificity ranges from 73% to 97%. The features of a lymph node involved with cancer include cortical thickening,
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of examination for the status of axillary nodes ranges from 35% to 82% and specificity ranges from 73% to 97%. The features of a lymph node involved with cancer include cortical thickening, change in shape of the node to more circular appearance, size larger Brunicardi_Ch17_p0541-p0612.indd 57101/03/19 5:05 PM 572SPECIFIC CONSIDERATIONSPART IIABFigure 17-24. Ultrasonography images of benign breast tumors. A. Fibroadenoma. B. Intraductal papilloma (see arrow). (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)ABCFigure 17-23. Breast cyst. A. Simple cyst. Ultrasound image of the mass shows it to be anechoic with a well-defined back wall, characteristic of a cyst. B. Complex solid and cystic mass. C. Complex solid and cystic mass characteristic of intracystic papillary tumor. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby,
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Surgery_Schwartz. of examination for the status of axillary nodes ranges from 35% to 82% and specificity ranges from 73% to 97%. The features of a lymph node involved with cancer include cortical thickening, change in shape of the node to more circular appearance, size larger Brunicardi_Ch17_p0541-p0612.indd 57101/03/19 5:05 PM 572SPECIFIC CONSIDERATIONSPART IIABFigure 17-24. Ultrasonography images of benign breast tumors. A. Fibroadenoma. B. Intraductal papilloma (see arrow). (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)ABCFigure 17-23. Breast cyst. A. Simple cyst. Ultrasound image of the mass shows it to be anechoic with a well-defined back wall, characteristic of a cyst. B. Complex solid and cystic mass. C. Complex solid and cystic mass characteristic of intracystic papillary tumor. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby,
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solid and cystic mass characteristic of intracystic papillary tumor. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)than 10 mm, absence of a fatty hilum and hypoechoic internal echoes.153Magnetic Resonance Imaging. In the process of evaluating magnetic resonance imaging (MRI) as a means of character-izing mammographic abnormalities, additional breast lesions have been detected. However, in the circumstance of negative findings on both mammography and physical examination, the probability of a breast cancer being diagnosed by MRI is extremely low. There is current interest in the use of MRI to screen the breasts of high-risk women and of women with a newly diagnosed breast cancer. In the first case, women who have a strong family history of breast cancer or who carry known genetic mutations require screening at an early age because mammographic evaluation is limited due to the increased breast density
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Surgery_Schwartz. solid and cystic mass characteristic of intracystic papillary tumor. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)than 10 mm, absence of a fatty hilum and hypoechoic internal echoes.153Magnetic Resonance Imaging. In the process of evaluating magnetic resonance imaging (MRI) as a means of character-izing mammographic abnormalities, additional breast lesions have been detected. However, in the circumstance of negative findings on both mammography and physical examination, the probability of a breast cancer being diagnosed by MRI is extremely low. There is current interest in the use of MRI to screen the breasts of high-risk women and of women with a newly diagnosed breast cancer. In the first case, women who have a strong family history of breast cancer or who carry known genetic mutations require screening at an early age because mammographic evaluation is limited due to the increased breast density
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who have a strong family history of breast cancer or who carry known genetic mutations require screening at an early age because mammographic evaluation is limited due to the increased breast density in younger women. In the second case, an MRI study of the contralateral breast in women with a known breast cancer has shown a contralateral breast cancer in 5.7% of these women (Fig. 17-27). MRI can also detect additional tumors in the index breast (multifocal or multicen-tric disease) that may be missed on routine breast imaging and this may alter surgical decision making (Fig. 17-28). In fact, MRI has been advocated by some for routine use in surgical treatment planning based on the fact that additional disease can be identified with this advanced imaging modality and the Brunicardi_Ch17_p0541-p0612.indd 57201/03/19 5:05 PM 573THE BREASTCHAPTER 17Figure 17-25. Ultrasonography images of malignant breast lesions. A. 25 mm irregular mass. B. Ultrasound 30 mm mass anterior to an
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Surgery_Schwartz. who have a strong family history of breast cancer or who carry known genetic mutations require screening at an early age because mammographic evaluation is limited due to the increased breast density in younger women. In the second case, an MRI study of the contralateral breast in women with a known breast cancer has shown a contralateral breast cancer in 5.7% of these women (Fig. 17-27). MRI can also detect additional tumors in the index breast (multifocal or multicen-tric disease) that may be missed on routine breast imaging and this may alter surgical decision making (Fig. 17-28). In fact, MRI has been advocated by some for routine use in surgical treatment planning based on the fact that additional disease can be identified with this advanced imaging modality and the Brunicardi_Ch17_p0541-p0612.indd 57201/03/19 5:05 PM 573THE BREASTCHAPTER 17Figure 17-25. Ultrasonography images of malignant breast lesions. A. 25 mm irregular mass. B. Ultrasound 30 mm mass anterior to an
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57201/03/19 5:05 PM 573THE BREASTCHAPTER 17Figure 17-25. Ultrasonography images of malignant breast lesions. A. 25 mm irregular mass. B. Ultrasound 30 mm mass anterior to an implant. C. Ultrasound breast cancer with calcification. D. Ultrasound shows a 9 mm spiculated mass (see arrow) with attenuation. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)extent of disease may be more accurately assessed. A random-ized trial performed in the United Kingdom (COMICE trial) that enrolled 1623 women did not show a decrease in rates of reoperation in those women randomized to undergo MRI in addition to mammography and ultrasonography (19%) com-pared to those undergoing standard breast imaging without MRI (19%).154 Houssami and colleagues performed a meta-analysis including two randomized trials and seven compara-tive cohort studies to examine the effect of preoperative MRI compared to standard preoperative
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Surgery_Schwartz. 57201/03/19 5:05 PM 573THE BREASTCHAPTER 17Figure 17-25. Ultrasonography images of malignant breast lesions. A. 25 mm irregular mass. B. Ultrasound 30 mm mass anterior to an implant. C. Ultrasound breast cancer with calcification. D. Ultrasound shows a 9 mm spiculated mass (see arrow) with attenuation. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)extent of disease may be more accurately assessed. A random-ized trial performed in the United Kingdom (COMICE trial) that enrolled 1623 women did not show a decrease in rates of reoperation in those women randomized to undergo MRI in addition to mammography and ultrasonography (19%) com-pared to those undergoing standard breast imaging without MRI (19%).154 Houssami and colleagues performed a meta-analysis including two randomized trials and seven compara-tive cohort studies to examine the effect of preoperative MRI compared to standard preoperative
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Houssami and colleagues performed a meta-analysis including two randomized trials and seven compara-tive cohort studies to examine the effect of preoperative MRI compared to standard preoperative evaluation on surgical out-comes.155 They reported that the use of MRI was associated with increased mastectomy rates. This is problematic because there is no evidence that the additional disease detected by MRI is of clinical or biologic significance, particularly in light of the low local-regional failure rates currently reported in patients undergoing breast conserving surgery who receive whole breast irradiation and systemic therapies. There is an ongoing trial in the Alliance for Clinical Trials in Oncology that is randomizing patients to preoperative MRI vs. standard imaging to assess the impact of MRI on local regional recur-rence rates in patients with triple receptor negative and HER2 positive breast cancers.The use of dedicated breast coils is mandatory in the MRI imaging of the
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Surgery_Schwartz. Houssami and colleagues performed a meta-analysis including two randomized trials and seven compara-tive cohort studies to examine the effect of preoperative MRI compared to standard preoperative evaluation on surgical out-comes.155 They reported that the use of MRI was associated with increased mastectomy rates. This is problematic because there is no evidence that the additional disease detected by MRI is of clinical or biologic significance, particularly in light of the low local-regional failure rates currently reported in patients undergoing breast conserving surgery who receive whole breast irradiation and systemic therapies. There is an ongoing trial in the Alliance for Clinical Trials in Oncology that is randomizing patients to preoperative MRI vs. standard imaging to assess the impact of MRI on local regional recur-rence rates in patients with triple receptor negative and HER2 positive breast cancers.The use of dedicated breast coils is mandatory in the MRI imaging of the
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impact of MRI on local regional recur-rence rates in patients with triple receptor negative and HER2 positive breast cancers.The use of dedicated breast coils is mandatory in the MRI imaging of the breast. A BIRADS lexicon is assigned to each examination and an abnormality noted on MRI that is not seen on mammography requires a focused ultrasound examination for further assessment. If the abnormality is not seen on corre-sponding mammogram or ultrasound, then MRI-guided biopsy is necessary. Some clinical scenarios where MRI may be use-ful include the evaluation of a patient who presents with nodal metastasis from breast cancer without an identifiable primary tumor; to assess response to therapy in the setting of neoadjuvant ABCDBrunicardi_Ch17_p0541-p0612.indd 57301/03/19 5:05 PM 574SPECIFIC CONSIDERATIONSPART IIFigure 17-26. Ultrasonography images of lymph nodes. A. Nor-mal axillary lymph node (see arrows). B. Indeterminate axillary lymph node. C. Malignant appearing axillary
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Surgery_Schwartz. impact of MRI on local regional recur-rence rates in patients with triple receptor negative and HER2 positive breast cancers.The use of dedicated breast coils is mandatory in the MRI imaging of the breast. A BIRADS lexicon is assigned to each examination and an abnormality noted on MRI that is not seen on mammography requires a focused ultrasound examination for further assessment. If the abnormality is not seen on corre-sponding mammogram or ultrasound, then MRI-guided biopsy is necessary. Some clinical scenarios where MRI may be use-ful include the evaluation of a patient who presents with nodal metastasis from breast cancer without an identifiable primary tumor; to assess response to therapy in the setting of neoadjuvant ABCDBrunicardi_Ch17_p0541-p0612.indd 57301/03/19 5:05 PM 574SPECIFIC CONSIDERATIONSPART IIFigure 17-26. Ultrasonography images of lymph nodes. A. Nor-mal axillary lymph node (see arrows). B. Indeterminate axillary lymph node. C. Malignant appearing axillary
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CONSIDERATIONSPART IIFigure 17-26. Ultrasonography images of lymph nodes. A. Nor-mal axillary lymph node (see arrows). B. Indeterminate axillary lymph node. C. Malignant appearing axillary lymph node. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)ABCsystemic treatment; to select patients for partial breast irradia-tion techniques; and evaluation of the treated breast for tumor recurrence.Breast BiopsyNonpalpable Lesions. Image-guided breast biopsy specimens are frequently required to diagnose nonpalpable lesions.156 Ultrasound localization techniques are used when a mass is present, whereas stereotactic techniques are used when no mass is present (microcalcifications or architectural distortion only). The combination of diagnostic mammography, ultrasound or stereotactic localization, and fine-needle aspiration (FNA) biopsy achieves almost 100% accuracy in the preoperative diag-nosis of breast cancer.
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Surgery_Schwartz. CONSIDERATIONSPART IIFigure 17-26. Ultrasonography images of lymph nodes. A. Nor-mal axillary lymph node (see arrows). B. Indeterminate axillary lymph node. C. Malignant appearing axillary lymph node. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)ABCsystemic treatment; to select patients for partial breast irradia-tion techniques; and evaluation of the treated breast for tumor recurrence.Breast BiopsyNonpalpable Lesions. Image-guided breast biopsy specimens are frequently required to diagnose nonpalpable lesions.156 Ultrasound localization techniques are used when a mass is present, whereas stereotactic techniques are used when no mass is present (microcalcifications or architectural distortion only). The combination of diagnostic mammography, ultrasound or stereotactic localization, and fine-needle aspiration (FNA) biopsy achieves almost 100% accuracy in the preoperative diag-nosis of breast cancer.
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combination of diagnostic mammography, ultrasound or stereotactic localization, and fine-needle aspiration (FNA) biopsy achieves almost 100% accuracy in the preoperative diag-nosis of breast cancer. However, although FNA biopsy permits cytologic evaluation, core-needle permits the analysis of breast tissue architecture and allows the pathologist to determine whether invasive cancer is present. This permits the surgeon and patient to discuss the specific management of a breast cancer before therapy begins. Core-needle biopsy is preferred over open biopsy for nonpalpable breast lesions because a single sur-gical procedure can be planned based on the results of the core biopsy. The advantages of core-needle biopsy include a low complication rate, minimal scarring, and a lower cost compared with excisional breast biopsy.Palpable Lesions. FNA or core biopsy of a palpable breast mass can usually be performed in an outpatient setting.157 A 1.5-in, 22-gauge needle attached to a 10-mL syringe
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Surgery_Schwartz. combination of diagnostic mammography, ultrasound or stereotactic localization, and fine-needle aspiration (FNA) biopsy achieves almost 100% accuracy in the preoperative diag-nosis of breast cancer. However, although FNA biopsy permits cytologic evaluation, core-needle permits the analysis of breast tissue architecture and allows the pathologist to determine whether invasive cancer is present. This permits the surgeon and patient to discuss the specific management of a breast cancer before therapy begins. Core-needle biopsy is preferred over open biopsy for nonpalpable breast lesions because a single sur-gical procedure can be planned based on the results of the core biopsy. The advantages of core-needle biopsy include a low complication rate, minimal scarring, and a lower cost compared with excisional breast biopsy.Palpable Lesions. FNA or core biopsy of a palpable breast mass can usually be performed in an outpatient setting.157 A 1.5-in, 22-gauge needle attached to a 10-mL syringe
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excisional breast biopsy.Palpable Lesions. FNA or core biopsy of a palpable breast mass can usually be performed in an outpatient setting.157 A 1.5-in, 22-gauge needle attached to a 10-mL syringe or a 14-gauge core biopsy needle is used. For FNA, use of a syringe holder 7Figure 17-27. MRI examination revealing contralateral breast cancer (see arrows) in a patient diag-nosed with unilateral breast cancer on mammography (two arrows). (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 57401/03/19 5:05 PM 575THE BREASTCHAPTER 17enables the surgeon performing the FNA biopsy to control the syringe and needle with one hand while positioning the breast mass with the opposite hand. After the needle is placed in the mass, suction is applied while the needle is moved back and forth within the mass. Once cellular material is seen at the hub of the needle, the suction is released
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Surgery_Schwartz. excisional breast biopsy.Palpable Lesions. FNA or core biopsy of a palpable breast mass can usually be performed in an outpatient setting.157 A 1.5-in, 22-gauge needle attached to a 10-mL syringe or a 14-gauge core biopsy needle is used. For FNA, use of a syringe holder 7Figure 17-27. MRI examination revealing contralateral breast cancer (see arrows) in a patient diag-nosed with unilateral breast cancer on mammography (two arrows). (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 57401/03/19 5:05 PM 575THE BREASTCHAPTER 17enables the surgeon performing the FNA biopsy to control the syringe and needle with one hand while positioning the breast mass with the opposite hand. After the needle is placed in the mass, suction is applied while the needle is moved back and forth within the mass. Once cellular material is seen at the hub of the needle, the suction is released
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After the needle is placed in the mass, suction is applied while the needle is moved back and forth within the mass. Once cellular material is seen at the hub of the needle, the suction is released and the needle is with-drawn. The cellular material is then expressed onto microscope slides. Both air-dried and 95% ethanol–fixed microscopic sec-tions are prepared for analysis. When a breast mass is clinically and mammographically suspicious, the sensitivity and specific-ity of FNA biopsy approaches 100%. Core-needle biopsy of palpable breast masses is performed using a 14-gauge needle, such as the Tru-Cut needle. Automated devices also are avail-able. Vacuum-assisted core biopsy devices (with 8–10 gauge needles) are commonly utilized with image guidance where between 4 and 12 samples can be acquired at different posi-tions within a mass, area of architectural distortion or micro-calcifications. If the target lesion was microcalcifications, the specimen should be radiographed to confirm
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Surgery_Schwartz. After the needle is placed in the mass, suction is applied while the needle is moved back and forth within the mass. Once cellular material is seen at the hub of the needle, the suction is released and the needle is with-drawn. The cellular material is then expressed onto microscope slides. Both air-dried and 95% ethanol–fixed microscopic sec-tions are prepared for analysis. When a breast mass is clinically and mammographically suspicious, the sensitivity and specific-ity of FNA biopsy approaches 100%. Core-needle biopsy of palpable breast masses is performed using a 14-gauge needle, such as the Tru-Cut needle. Automated devices also are avail-able. Vacuum-assisted core biopsy devices (with 8–10 gauge needles) are commonly utilized with image guidance where between 4 and 12 samples can be acquired at different posi-tions within a mass, area of architectural distortion or micro-calcifications. If the target lesion was microcalcifications, the specimen should be radiographed to confirm
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acquired at different posi-tions within a mass, area of architectural distortion or micro-calcifications. If the target lesion was microcalcifications, the specimen should be radiographed to confirm appropriate sam-pling. A radiopaque marker should be placed at the site of the biopsy to mark the area for future intervention. In some cases the entire lesion is removed with the biopsy technique and clip placement allows for accurate targeting of the site for surgi-cal resection. Tissue specimens are placed in formalin and then processed to paraffin blocks. Although the false-negative rate for core-needle biopsy specimens is very low, a tissue speci-men that does not show breast cancer cannot conclusively rule out that diagnosis because a sampling error may have occurred. The clinical, radiographic, and pathologic findings should be in concordance. If the biopsy findings do not concur with the clinical and radiographic findings, the multidisciplinary team (including clinician,
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Surgery_Schwartz. acquired at different posi-tions within a mass, area of architectural distortion or micro-calcifications. If the target lesion was microcalcifications, the specimen should be radiographed to confirm appropriate sam-pling. A radiopaque marker should be placed at the site of the biopsy to mark the area for future intervention. In some cases the entire lesion is removed with the biopsy technique and clip placement allows for accurate targeting of the site for surgi-cal resection. Tissue specimens are placed in formalin and then processed to paraffin blocks. Although the false-negative rate for core-needle biopsy specimens is very low, a tissue speci-men that does not show breast cancer cannot conclusively rule out that diagnosis because a sampling error may have occurred. The clinical, radiographic, and pathologic findings should be in concordance. If the biopsy findings do not concur with the clinical and radiographic findings, the multidisciplinary team (including clinician,
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radiographic, and pathologic findings should be in concordance. If the biopsy findings do not concur with the clinical and radiographic findings, the multidisciplinary team (including clinician, radiologist, and pathologist) should review the findings and decide whether or not to recommend an image-guided or open biopsy to be certain that the target lesion has been adequately sampled for diagnosis.BREAST CANCER STAGING AND BIOMARKERSBreast Cancer StagingThe clinical stage of breast cancer is determined primarily through physical examination of the skin, breast tissue, and regional lymph nodes (axillary, supraclavicular, and internal mammary).158 However, clinical determination of axillary lymph node metastases has an accuracy of only 33%. Ultrasound (US) is more sensitive than physical examination alone in determining axillary lymph node involvement during preliminary staging of breast carcinoma. FNA or core biopsy of sonographically inde-terminate or suspicious lymph nodes can
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Surgery_Schwartz. radiographic, and pathologic findings should be in concordance. If the biopsy findings do not concur with the clinical and radiographic findings, the multidisciplinary team (including clinician, radiologist, and pathologist) should review the findings and decide whether or not to recommend an image-guided or open biopsy to be certain that the target lesion has been adequately sampled for diagnosis.BREAST CANCER STAGING AND BIOMARKERSBreast Cancer StagingThe clinical stage of breast cancer is determined primarily through physical examination of the skin, breast tissue, and regional lymph nodes (axillary, supraclavicular, and internal mammary).158 However, clinical determination of axillary lymph node metastases has an accuracy of only 33%. Ultrasound (US) is more sensitive than physical examination alone in determining axillary lymph node involvement during preliminary staging of breast carcinoma. FNA or core biopsy of sonographically inde-terminate or suspicious lymph nodes can
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examination alone in determining axillary lymph node involvement during preliminary staging of breast carcinoma. FNA or core biopsy of sonographically inde-terminate or suspicious lymph nodes can provide a more defini-tive diagnosis than US alone.153,159 Pathologic stage combines the findings from pathologic examination of the resected pri-mary breast cancer and axillary or other regional lymph nodes. Fisher and colleagues found that accurate predictions regarding the occurrence of distant metastases were possible after resec-tion and pathologic analysis of 10 or more levels I and II axillary lymph nodes.160 A frequently used staging system is the TNM (tumor, nodes, and metastasis) system. The American Joint Committee on Cancer (AJCC) has recently modified the TNM system for breast cancer to include both anatomic and biologic factors161 (Tables 17-10 and 17-11). Koscielny and colleagues demonstrated that tumor size correlates with the presence of axillary lymph node metastases (see
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Surgery_Schwartz. examination alone in determining axillary lymph node involvement during preliminary staging of breast carcinoma. FNA or core biopsy of sonographically inde-terminate or suspicious lymph nodes can provide a more defini-tive diagnosis than US alone.153,159 Pathologic stage combines the findings from pathologic examination of the resected pri-mary breast cancer and axillary or other regional lymph nodes. Fisher and colleagues found that accurate predictions regarding the occurrence of distant metastases were possible after resec-tion and pathologic analysis of 10 or more levels I and II axillary lymph nodes.160 A frequently used staging system is the TNM (tumor, nodes, and metastasis) system. The American Joint Committee on Cancer (AJCC) has recently modified the TNM system for breast cancer to include both anatomic and biologic factors161 (Tables 17-10 and 17-11). Koscielny and colleagues demonstrated that tumor size correlates with the presence of axillary lymph node metastases (see
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Surgery_Schwartz_3889
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Surgery_Schwartz
|
to include both anatomic and biologic factors161 (Tables 17-10 and 17-11). Koscielny and colleagues demonstrated that tumor size correlates with the presence of axillary lymph node metastases (see Fig. 17-14B). Others have shown an association between tumor size, axillary lymph node metastases, and disease-free survival. One of the most important predictors of 10and 20-year survival rates in breast cancer is the number of axillary lymph nodes involved with metastatic disease. Routine biopsy of internal mammary lymph nodes is not generally performed; however, it has been reported that in the context of a “triple node” biopsy approach either the internal mammary node or a low axillary node when positive alone carried the same prognostic weight. When both nodes were positive, the prognosis declined to the level associated with apical node positivity. A double node biopsy of the low axil-lary node and either the apical or the internal mammary node gave the same maximum prognostic
|
Surgery_Schwartz. to include both anatomic and biologic factors161 (Tables 17-10 and 17-11). Koscielny and colleagues demonstrated that tumor size correlates with the presence of axillary lymph node metastases (see Fig. 17-14B). Others have shown an association between tumor size, axillary lymph node metastases, and disease-free survival. One of the most important predictors of 10and 20-year survival rates in breast cancer is the number of axillary lymph nodes involved with metastatic disease. Routine biopsy of internal mammary lymph nodes is not generally performed; however, it has been reported that in the context of a “triple node” biopsy approach either the internal mammary node or a low axillary node when positive alone carried the same prognostic weight. When both nodes were positive, the prognosis declined to the level associated with apical node positivity. A double node biopsy of the low axil-lary node and either the apical or the internal mammary node gave the same maximum prognostic
|
Surgery_Schwartz_3890
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Surgery_Schwartz
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declined to the level associated with apical node positivity. A double node biopsy of the low axil-lary node and either the apical or the internal mammary node gave the same maximum prognostic information as a triple node biopsy.162 With the advent of sentinel lymph node dissection and the use of preoperative lymphoscintigraphy for localization of the sentinel nodes, surgeons have again begun to biopsy the internal mammary nodes but in a more targeted manner. The 8th edition of the AJCC staging system does allow for staging based on findings from the internal mammary sentinel nodes.163 Drainage to the internal mammary nodes is more frequent with central and medial quadrant cancers. Clinical or pathologic evi-dence of metastatic spread to supraclavicular lymph nodes is no longer considered stage IV disease, but routine scalene or supraclavicular lymph node biopsy is not indicated.BiomarkersBreast cancer biomarkers are of several types. Risk factor biomarkers are those associated with
|
Surgery_Schwartz. declined to the level associated with apical node positivity. A double node biopsy of the low axil-lary node and either the apical or the internal mammary node gave the same maximum prognostic information as a triple node biopsy.162 With the advent of sentinel lymph node dissection and the use of preoperative lymphoscintigraphy for localization of the sentinel nodes, surgeons have again begun to biopsy the internal mammary nodes but in a more targeted manner. The 8th edition of the AJCC staging system does allow for staging based on findings from the internal mammary sentinel nodes.163 Drainage to the internal mammary nodes is more frequent with central and medial quadrant cancers. Clinical or pathologic evi-dence of metastatic spread to supraclavicular lymph nodes is no longer considered stage IV disease, but routine scalene or supraclavicular lymph node biopsy is not indicated.BiomarkersBreast cancer biomarkers are of several types. Risk factor biomarkers are those associated with
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Surgery_Schwartz_3891
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Surgery_Schwartz
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stage IV disease, but routine scalene or supraclavicular lymph node biopsy is not indicated.BiomarkersBreast cancer biomarkers are of several types. Risk factor biomarkers are those associated with increased cancer risk.164-168 These include familial clustering and inherited germline abnormalities, proliferative breast disease with atypia, and mammographic density. Exposure biomarkers are a subset of risk factors that include measures of carcinogen exposure such as DNA adducts. Surrogate endpoint biomarkers are biologic alterations in tissue that occur between cancer initiation and development. These biomarkers are used as endpoints in short-term chemoprevention trials and include histologic changes, indices of proliferation, and genetic alterations leading to cancer. Prognostic biomarkers provide information regarding Figure 17-28. MRI imaging of the breast reveal-ing multifocal tumors not detected with standard breast imaging. (Used with permission from Dr. Anne Turnbull, Consultant
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Surgery_Schwartz. stage IV disease, but routine scalene or supraclavicular lymph node biopsy is not indicated.BiomarkersBreast cancer biomarkers are of several types. Risk factor biomarkers are those associated with increased cancer risk.164-168 These include familial clustering and inherited germline abnormalities, proliferative breast disease with atypia, and mammographic density. Exposure biomarkers are a subset of risk factors that include measures of carcinogen exposure such as DNA adducts. Surrogate endpoint biomarkers are biologic alterations in tissue that occur between cancer initiation and development. These biomarkers are used as endpoints in short-term chemoprevention trials and include histologic changes, indices of proliferation, and genetic alterations leading to cancer. Prognostic biomarkers provide information regarding Figure 17-28. MRI imaging of the breast reveal-ing multifocal tumors not detected with standard breast imaging. (Used with permission from Dr. Anne Turnbull, Consultant
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Surgery_Schwartz_3892
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Surgery_Schwartz
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provide information regarding Figure 17-28. MRI imaging of the breast reveal-ing multifocal tumors not detected with standard breast imaging. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 57501/03/19 5:05 PM 576SPECIFIC CONSIDERATIONSPART IITable 17-10TNM staging system for breast cancerPrimary tumor (T)The T classification of the primary tumor is the same regardless of whether it is based on clinical or pathologic criteria, or both. Size should be measured to the nearest millimeter. If the tumor size is slightly less than or greater than a cutoff for a given T classification, it is recommended that the size be rounded to the millimeter reading that is closest to the cutoff. For example, a reported size of 1.1 mm is reported as 1 mm, or a size of 2.01 cm is reported as 2.0 cm. Designation should be made with the subscript “c” or “p” modifier to indicate whether
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Surgery_Schwartz. provide information regarding Figure 17-28. MRI imaging of the breast reveal-ing multifocal tumors not detected with standard breast imaging. (Used with permission from Dr. Anne Turnbull, Consultant Radiologist/Director of Breast Screening, Royal Derby Hospital, Derby, UK.)Brunicardi_Ch17_p0541-p0612.indd 57501/03/19 5:05 PM 576SPECIFIC CONSIDERATIONSPART IITable 17-10TNM staging system for breast cancerPrimary tumor (T)The T classification of the primary tumor is the same regardless of whether it is based on clinical or pathologic criteria, or both. Size should be measured to the nearest millimeter. If the tumor size is slightly less than or greater than a cutoff for a given T classification, it is recommended that the size be rounded to the millimeter reading that is closest to the cutoff. For example, a reported size of 1.1 mm is reported as 1 mm, or a size of 2.01 cm is reported as 2.0 cm. Designation should be made with the subscript “c” or “p” modifier to indicate whether
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Surgery_Schwartz_3893
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Surgery_Schwartz
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cutoff. For example, a reported size of 1.1 mm is reported as 1 mm, or a size of 2.01 cm is reported as 2.0 cm. Designation should be made with the subscript “c” or “p” modifier to indicate whether the T classification was determined by clinical (physical examination or radiologic) or pathologic measurements, respectively. In general, pathologic determination should take precedence over clinical determination of T size.TXT0Tis (DCIS)*Tis (Paget)T1 T1mi T1a T1b T1cT2T3T4 T4a T4b T4c T4dPrimary tumor cannot be assessedNo evidence of primary tumorDuctal carcinoma in situPaget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted.Tumor ≤20 mm in greatest dimensionTumor ≤1 mm in greatest dimensionTumor >1 mm
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Surgery_Schwartz. cutoff. For example, a reported size of 1.1 mm is reported as 1 mm, or a size of 2.01 cm is reported as 2.0 cm. Designation should be made with the subscript “c” or “p” modifier to indicate whether the T classification was determined by clinical (physical examination or radiologic) or pathologic measurements, respectively. In general, pathologic determination should take precedence over clinical determination of T size.TXT0Tis (DCIS)*Tis (Paget)T1 T1mi T1a T1b T1cT2T3T4 T4a T4b T4c T4dPrimary tumor cannot be assessedNo evidence of primary tumorDuctal carcinoma in situPaget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted.Tumor ≤20 mm in greatest dimensionTumor ≤1 mm in greatest dimensionTumor >1 mm
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Surgery_Schwartz_3894
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Surgery_Schwartz
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on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted.Tumor ≤20 mm in greatest dimensionTumor ≤1 mm in greatest dimensionTumor >1 mm but ≤5 mm in greatest dimension (round any measurement >l.0–1.9 mm to 2 mm).Tumor >5 mim but ≤10 mm in greatest dimensionTumor >10 mm but ≤20 mm in greatest dimensionTumor >20 mm but ≤50 mm in greatest dimensionTumor >50 mm in greatest dimensionTumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4Extension to the chest wall; invasion or adherence to pectoralis muscle in the absence of invasion of chest wall structures does not qualify as T4Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (including peau d’orange) of the skin that does not meet the criteria for inflammatory carcinomaBoth T4a and T4b are presentInflammatory carcinoma (see section “Rules for
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Surgery_Schwartz. on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted.Tumor ≤20 mm in greatest dimensionTumor ≤1 mm in greatest dimensionTumor >1 mm but ≤5 mm in greatest dimension (round any measurement >l.0–1.9 mm to 2 mm).Tumor >5 mim but ≤10 mm in greatest dimensionTumor >10 mm but ≤20 mm in greatest dimensionTumor >20 mm but ≤50 mm in greatest dimensionTumor >50 mm in greatest dimensionTumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4Extension to the chest wall; invasion or adherence to pectoralis muscle in the absence of invasion of chest wall structures does not qualify as T4Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (including peau d’orange) of the skin that does not meet the criteria for inflammatory carcinomaBoth T4a and T4b are presentInflammatory carcinoma (see section “Rules for
|
Surgery_Schwartz_3895
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Surgery_Schwartz
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nodules and/or edema (including peau d’orange) of the skin that does not meet the criteria for inflammatory carcinomaBoth T4a and T4b are presentInflammatory carcinoma (see section “Rules for Classification”)*Note: Lobular carcinoma in situ (LCIS) is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th edition.Regional lymph nodes—Clinical (N)cNX*cN0cN1 cN1mi**cN2 cN2a cN2bcN3 cN3a cN3b cN3cRegional lymph nodes cannot be assessed (e.g., previously removed)No regional lymph node metastases (by imaging or clinical examination)Metastases to movable ipsilateral Level I, II axillary lymph node(s)Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm)Metastases in ipsilateral Level I, II axillary lymph nodes that are clinically fixed or matted;or in ipsilateral internal mammary nodes in the absence of axillary lymph node metastasesMetastases in ipsilateral Level I, II axillary lymph nodes fixed to one another (matted) or
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Surgery_Schwartz. nodules and/or edema (including peau d’orange) of the skin that does not meet the criteria for inflammatory carcinomaBoth T4a and T4b are presentInflammatory carcinoma (see section “Rules for Classification”)*Note: Lobular carcinoma in situ (LCIS) is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th edition.Regional lymph nodes—Clinical (N)cNX*cN0cN1 cN1mi**cN2 cN2a cN2bcN3 cN3a cN3b cN3cRegional lymph nodes cannot be assessed (e.g., previously removed)No regional lymph node metastases (by imaging or clinical examination)Metastases to movable ipsilateral Level I, II axillary lymph node(s)Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm)Metastases in ipsilateral Level I, II axillary lymph nodes that are clinically fixed or matted;or in ipsilateral internal mammary nodes in the absence of axillary lymph node metastasesMetastases in ipsilateral Level I, II axillary lymph nodes fixed to one another (matted) or
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Surgery_Schwartz_3896
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Surgery_Schwartz
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fixed or matted;or in ipsilateral internal mammary nodes in the absence of axillary lymph node metastasesMetastases in ipsilateral Level I, II axillary lymph nodes fixed to one another (matted) or to other structuresMetastases only in ipsilateral internal mammary nodes in the absence of axillary lymph node metastasesMetastases in ipsilateral infraclavicular (Level III axillary) lymph node(s) with or without Level I, II axillary lymph node involvement;or in ipsilateral internal mammary lymph node(s) with Level I, II axillary lymph node metastases;or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvementMetastases in ipsilateral infraclavicular lymph node(s)Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)Metastases in ipsilateral supraclavicular lymph node(s)Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or
|
Surgery_Schwartz. fixed or matted;or in ipsilateral internal mammary nodes in the absence of axillary lymph node metastasesMetastases in ipsilateral Level I, II axillary lymph nodes fixed to one another (matted) or to other structuresMetastases only in ipsilateral internal mammary nodes in the absence of axillary lymph node metastasesMetastases in ipsilateral infraclavicular (Level III axillary) lymph node(s) with or without Level I, II axillary lymph node involvement;or in ipsilateral internal mammary lymph node(s) with Level I, II axillary lymph node metastases;or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvementMetastases in ipsilateral infraclavicular lymph node(s)Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s)Metastases in ipsilateral supraclavicular lymph node(s)Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or
|
Surgery_Schwartz_3897
|
Surgery_Schwartz
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lymph node(s)Metastases in ipsilateral supraclavicular lymph node(s)Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or fine needle aspiration/core needle biopsy respectively.*the cNX category is used sparingly in cases where regional lymph nodes have previously been surgically removed or where there is no documentation of physical examination of the axilla.**cN1mi is rarely used but may be appropriate in cases where sentinel node biopsy is performed before tumor resection, most likely to occur in cases treated with neoadjuvant therapy.(Continued)Brunicardi_Ch17_p0541-p0612.indd 57601/03/19 5:05 PM 577THE BREASTCHAPTER 17Table 17-10TNM staging system for breast cancerRegional lymph nodes—Pathologic (pN)pNXpN0 pN0(i+) pN0(mol+)pN1 pN1mi pN1a pN1b pN1cRegional lymph nodes cannot be assessed (e.g., not removed for pathological study or previously removed)No regional lymph node metastasis identified or ITCs
|
Surgery_Schwartz. lymph node(s)Metastases in ipsilateral supraclavicular lymph node(s)Note: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or fine needle aspiration/core needle biopsy respectively.*the cNX category is used sparingly in cases where regional lymph nodes have previously been surgically removed or where there is no documentation of physical examination of the axilla.**cN1mi is rarely used but may be appropriate in cases where sentinel node biopsy is performed before tumor resection, most likely to occur in cases treated with neoadjuvant therapy.(Continued)Brunicardi_Ch17_p0541-p0612.indd 57601/03/19 5:05 PM 577THE BREASTCHAPTER 17Table 17-10TNM staging system for breast cancerRegional lymph nodes—Pathologic (pN)pNXpN0 pN0(i+) pN0(mol+)pN1 pN1mi pN1a pN1b pN1cRegional lymph nodes cannot be assessed (e.g., not removed for pathological study or previously removed)No regional lymph node metastasis identified or ITCs
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Surgery_Schwartz_3898
|
Surgery_Schwartz
|
lymph nodes cannot be assessed (e.g., not removed for pathological study or previously removed)No regional lymph node metastasis identified or ITCs onlyITCs only (malignant cell clusters no larger than 0.2 mm) in regional lymph node(s)Positive molecular findings by reverse transcriptase polymerase chain reaction (RT-PCR); no ITCs detectedMicrometastases; or metastases in 1–3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsyMicrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm)Metastases in 1–3 axillary lymph nodes, at least one metastasis larger than 2.0 mmMetastases in ipsilateral internal mammary sentinel nodes, excluding ITCspN1a and pNlb combinedpN2 pN2a pN2bpN3 pN3a pN3b pN3cMetastases in 4–9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastasesMetastases in 4–9 axillary
|
Surgery_Schwartz. lymph nodes cannot be assessed (e.g., not removed for pathological study or previously removed)No regional lymph node metastasis identified or ITCs onlyITCs only (malignant cell clusters no larger than 0.2 mm) in regional lymph node(s)Positive molecular findings by reverse transcriptase polymerase chain reaction (RT-PCR); no ITCs detectedMicrometastases; or metastases in 1–3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsyMicrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm)Metastases in 1–3 axillary lymph nodes, at least one metastasis larger than 2.0 mmMetastases in ipsilateral internal mammary sentinel nodes, excluding ITCspN1a and pNlb combinedpN2 pN2a pN2bpN3 pN3a pN3b pN3cMetastases in 4–9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastasesMetastases in 4–9 axillary
|
Surgery_Schwartz_3899
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Surgery_Schwartz
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in 4–9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastasesMetastases in 4–9 axillary lymph nodes (at least one tumor deposit larger than 2.0 mm)Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary nodesMetastases in 10 or more axillary lymph nodes;or in infraclavicular (Level III axillary) lymph nodes;or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive Level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodesMetastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (Level III axillary lymph)
|
Surgery_Schwartz. in 4–9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastasesMetastases in 4–9 axillary lymph nodes (at least one tumor deposit larger than 2.0 mm)Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary nodesMetastases in 10 or more axillary lymph nodes;or in infraclavicular (Level III axillary) lymph nodes;or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive Level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodesMetastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (Level III axillary lymph)
|
Surgery_Schwartz_3900
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Surgery_Schwartz
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ipsilateral supraclavicular lymph nodesMetastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (Level III axillary lymph) nodespNla or pN2a in the presence of cN2b (positive internal mammary nodes by imaging); or pN2a in the presence of pNlbMetastases in ipsilateral supraclavicular lymph nodesNote: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or FNA/core needle biopsy respectively, with NO further resection of nodes.Distant metastasis (M)M0 cM0(i+)cM1pM1No clinical or radiographic evidence of distant metastases*No clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits no larger than 0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastasesDistant metastases detected by
|
Surgery_Schwartz. ipsilateral supraclavicular lymph nodesMetastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (Level III axillary lymph) nodespNla or pN2a in the presence of cN2b (positive internal mammary nodes by imaging); or pN2a in the presence of pNlbMetastases in ipsilateral supraclavicular lymph nodesNote: (sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or FNA/core needle biopsy respectively, with NO further resection of nodes.Distant metastasis (M)M0 cM0(i+)cM1pM1No clinical or radiographic evidence of distant metastases*No clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits no larger than 0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastasesDistant metastases detected by
|
Surgery_Schwartz_3901
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Surgery_Schwartz
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microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastasesDistant metastases detected by clinical and radiographic meansAny histologically proven metastases in distant organs; or if in non-regional nodes, metastases greater than 0.2 mmUsed with the permission of the American College of Surgeons. Amin MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.(Continued)cancer outcome irrespective of therapy, whereas predictive bio-markers provide information regarding response to therapy.169 Candidate prognostic and predictive biomarkers and biologic targets for breast cancer include (a) the steroid hormone recep-tor pathway; (b) growth factors and growth factor receptors such as human epidermal growth factor receptor 2 (HER2)/neu, epidermal growth factor receptor (EGFR), transforming growth factor, platelet-derived growth factor, and the
|
Surgery_Schwartz. microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastasesDistant metastases detected by clinical and radiographic meansAny histologically proven metastases in distant organs; or if in non-regional nodes, metastases greater than 0.2 mmUsed with the permission of the American College of Surgeons. Amin MB, Edge SB, Greene FL, et al. (Eds.) AJCC Cancer Staging Manual, 8th Ed. Springer New York, 2017.(Continued)cancer outcome irrespective of therapy, whereas predictive bio-markers provide information regarding response to therapy.169 Candidate prognostic and predictive biomarkers and biologic targets for breast cancer include (a) the steroid hormone recep-tor pathway; (b) growth factors and growth factor receptors such as human epidermal growth factor receptor 2 (HER2)/neu, epidermal growth factor receptor (EGFR), transforming growth factor, platelet-derived growth factor, and the
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