Background: In the Ashkenazim, three recurrent germline mutations have been identified in the breast carcinoma susceptibility genes BRCA1 and BRCA2: 185delAG, 5382insC (BRCA1), and 6174delT (BRCA2). The frequency of these mutations in the general Ashkenazi population approaches 2%. There is little available controlled data comparing the characteristics of breast carcinoma arising in BRCA1 mutation carriers or BRCA2 mutation carriers with that arising in noncarriers, although such data would be relevant to the urgent clinical need to develop risk-reduction strategies for individuals at increased risk due to genetic factors.
Methods: The authors screened 149 unselected tumors arising in Ashkenazi Jewish women for the 185delAG, 5382insC, and 6174delT mutations and compared tumors arising in mutation carriers with tumors arising in noncarriers with respect to nuclear grade, steroid hormone receptor status, and axillary lymph node status.
Results: In the 149 cases, the authors found 17 BRCA1 mutations (11.4%; 95% confidence interval [ci], 6.8-17.6%), and 4 6174delT BRCA2 mutations (2.7%; 95% CI, 0.8-6.7%). Tumors from women with BRCA1 mutations were significantly less likely to be estrogen receptor positive (age-adjusted odds ratio [or]: 0.091; P < 0.001) and more likely to have a high nuclear grade (OR: 5.55; P 0.001) than tumors in which no mutation was identified. All four BRCA2 positive breast carcinoma specimens were estrogen receptor positive.
Conclusions: Breast carcinoma arising in Ashkenazim BRCA1 mutation carriers has adverse prognostic features relative to those arising in noncarriers in the same population. This may be relevant to the development of prevention and treatment strategies for these women. For example, if tamoxifen reduces the risk of breast carcinoma via its antiestrogenic effects, it is possible that this effect will be diminished in the largely estrogen receptor negative BRCA1-related hereditary breast carcinoma.