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Most breast cancers that occur in women with germline  BRCA1  mutations are estrogen receptor-negative (ER-) and also typically lack expression of progesterone receptor (PR) and HER2 overexpression. We undertook a study to assess the clinical factors that predict for an estrogen receptor positive (ER+) breast cancer in  BRCA1  mutation carriers and to characterize the pathologic features of these tumors.    Methods  Clinical characteristics of  BRCA1  carriers with 58 ER+ and 114 ER- first invasive breast cancers were compared. Pathologic features of  BRCA1  ER+ cancers were compared to those of  BRCA1  ER- cancers and to age-matched ER+ sporadic cancers.    Results   BRCA1  carriers aged ≥ 50 at diagnosis of first invasive breast cancer were more likely to have an ER+ cancer compared to those aged < 50 (57% vs 29%,  P  = 0.005). ER+  BRCA1  cancers were less likely than ER-  BRCA1  cancers to have " BRCA -associated" features such as high mitotic activity, geographic necrosis/fibrotic focus, and pushing margins (RR 0.06, 0.22, 0.24;  P  < 0.001, 0.02, 0.03 respectively). When compared to sporadic ER+ cancers, ER+  BRCA1  cancers were more often of invasive ductal type (RR 2.4,  P  = 0.03), with a high mitotic rate (RR 5.0,  P  = 0.006) and absent or mild lymphocytic infiltrate (RR 10.2,  P  = 0.04).    Conclusions   BRCA1  carriers who are older at first breast cancer diagnosis are more likely to have ER+ tumors than younger  BRCA1  carriers. These ER+ cancers appear pathologically "intermediate" between ER-  BRCA1  cancers and ER+ sporadic breast cancers raising the possibility that either some ER+  BRCA1  cancers are incidental or that there is a unique mechanism by which these cancers develop.

Estrogen receptor positive breast cancers in BRCA1 mutation carriers: clinical risk factors and pathologic features