Estrogen receptor positive breast cancers in BRCA1mutation carriers: clinical risk factors and pathologic features

Most breast cancers that occur in women with germline BRCA1mutations 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 BRCA1mutation carriers and to characterize the pathologic features of these tumors. Clinical characteristics of BRCA1carriers with 58 ER+ and 114 ER- first invasive breast cancers were compared. Pathologic features of BRCA1ER+ cancers were compared to those of BRCA1ER- cancers and to age-matched ER+ sporadic cancers. BRCA1carriers 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+ BRCA1cancers were less likely than ER- BRCA1cancers 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+ BRCA1cancers 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). BRCA1carriers who are older at first breast cancer diagnosis are more likely to have ER+ tumors than younger BRCA1carriers. These ER+ cancers appear pathologically "intermediate" between ER- BRCA1cancers and ER+ sporadic breast cancers raising the possibility that either some ER+ BRCA1cancers are incidental or that there is a unique mechanism by which these cancers develop.