BACKGROUND: The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population. The Ontario Familial Breast Cancer Registry collects clinical and family history data in familial breast carcinoma cases, and unselected Ashkenazi breast carcinomas, and acts as a tumor tissue repository. METHODS: Using this resource, we examined the tumor morphology, hormone receptor status, and HER-2/neu protein overexpression in Canadian Ashkenazi breast carcinoma patients whose germline BRCA1 mutation status is known. RESULTS: Thirty-eight tumors from 32 BRCA1 carriers and 354 tumors from 334 noncarriers were analyzed. The tumors in BRCA1 mutation carriers were more likely to be high grade (P < 0.0001) and estrogen receptor negative (P < 0.004). There was an increased frequency of typical medullary carcinomas in mutation carriers when all tumors were analyzed. However, this difference did not remain statistically significant when only the first tumor diagnosed in each patient was included in the analysis. There was no difference in HER-2/neu protein overexpression between the two groups overall (P = 0.07). However, when the analysis was restricted to Grade III tumors, there were significantly fewer HER-2/neu-positive tumors in the mutation carriers versus noncarriers (3.1% vs. 21.5%, P = 0.012). No significant differences were found in the incidence of lymph node status, progesterone receptor status, lymphatic vessel invasion, degree of lymphocytic infiltration, or in the presence of ductal carcinoma in situ associated with the invasive tumors. CONCLUSIONS: Increasing awareness of the morphologic and immunophenotypic features more commonly found in BRCA1-associated breast carcinomas may lead to a wider use of these characteristics in genetic screening programs and provide further clues to their pathogenesis. Copyright 2002 American Cancer Society.
BACKGROUND: The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population. The Ontario Familial Breast Cancer Registry collects clinical and family history data in familial breast carcinoma cases, and unselected Ashkenazi breast carcinomas, and acts as a tumor tissue repository. METHODS: Using this resource, we examined the tumor morphology, hormone receptor status, and HER-2/neu protein overexpression in Canadian Ashkenazi breast carcinomapatients whose germline BRCA1 mutation status is known. RESULTS: Thirty-eight tumors from 32 BRCA1 carriers and 354 tumors from 334 noncarriers were analyzed. The tumors in BRCA1 mutation carriers were more likely to be high grade (P < 0.0001) and estrogen receptor negative (P < 0.004). There was an increased frequency of typical medullary carcinomas in mutation carriers when all tumors were analyzed. However, this difference did not remain statistically significant when only the first tumor diagnosed in each patient was included in the analysis. There was no difference in HER-2/neu protein overexpression between the two groups overall (P = 0.07). However, when the analysis was restricted to Grade III tumors, there were significantly fewer HER-2/neu-positive tumors in the mutation carriers versus noncarriers (3.1% vs. 21.5%, P = 0.012). No significant differences were found in the incidence of lymph node status, progesterone receptor status, lymphatic vessel invasion, degree of lymphocytic infiltration, or in the presence of ductal carcinoma in situ associated with the invasive tumors. CONCLUSIONS: Increasing awareness of the morphologic and immunophenotypic features more commonly found in BRCA1-associated breast carcinomas may lead to a wider use of these characteristics in genetic screening programs and provide further clues to their pathogenesis. Copyright 2002 American Cancer Society.
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