Abstract
IntroductionMost 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.MethodsClinical 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.ResultsBRCA1 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).ConclusionsBRCA1 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.
Highlights
Most breast cancers that occur in women with germline BRCA1 mutations are estrogen receptornegative (ER-) and typically lack expression of progesterone receptor (PR) and HER2 overexpression
The combination of the triple-negative phenotype and the pathologic features described above have come to be considered characteristic of BRCA1-associated breast cancers, approximately 10 to 36% of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are, ER-positive (ER+) [4,6,8,14,15]
Little is known about these BRCA1-associated ER+ breast cancers or about the factors that predict for the ER status of breast cancers that develop in these women
Summary
Most breast cancers that occur in women with germline BRCA1 mutations are estrogen receptornegative (ER-) and typically lack expression of progesterone receptor (PR) and HER2 overexpression. Most breast cancers that occur in women with germline BRCA1 mutations are estrogen receptor-negative (ER-) and typically lack expression of progesterone receptor (PR) and human epidermal growth factor receptor (HER) 2 overexpression (so-called ‘triple-negative’ breast cancers) [1,2,3,4,5,6,7,8] These BRCA1-associated ER-tumors are most often high-grade invasive ductal carcinomas with a high mitotic rate that frequently exhibit other characteristic pathologic features including a prominent lymphocytic infiltrate, pushing or circumscribed margins, and geographic areas of necrosis or a central fibrotic focus [3,9,10]. This finding suggested that loss of BRCA1 may result in the accumulation of ER- breast stem cells, which are genetically unstable and more likely to undergo carcinogenesis
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