Characterization of estrogen receptor-positive breast cancers in BRCA1 mutation carriers.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #1105 Background: Invasive breast cancers (IBC) in BRCA1 mutation carriers are usually estrogen receptor (ER) negative (-) and more than 80% have a basal-like molecular phenotype. These tumors are typically poorly differentiated invasive ductal carcinomas with a high mitotic rate and frequently show a prominent lymphoid infiltrate, pushing or circumscribed margins, and geographic necrosis or a central fibrotic focus. However, some women with BRCA1 germline mutations develop ER positive (+) cancers; little is known about the characteristics of the ER+ tumors in this group. Design: We identified 41 ER+ IBC that developed in women with BRCA1 germline mutations with available pathologic material for review. The histologic features were analyzed in detail and compared with those of 45 ER- IBC that developed among BRCA1 mutation carriers. Results: Mean patient age was 46y for ER+ and 45y for ER- cases. Ninety percent of the ER+ cases and all the ER- cases were invasive ductal carcinomas or invasive carcinomas with ductal and lobular features. There were 2 mucinous and 2 tubular carcinomas in the ER+ group. The ER+ cancers exhibited a range of histologic grades: 12 (29.3%) were grade I, 10 (24.4%) grade II, and 18 (43.9%) grade III (1 case of microinvasive carcinoma could not be graded). In contrast, 43 of the 45 ER- cancers were grade III (95.6%) and 1 (2.2%) grade II (1 case of microinvasive carcinoma could not be graded). Histologic features commonly seen in association with ER- BRCA1 mutation-associated IBC were compared between the two groups and the results are summarized in the table. ![][1] Of note, a brisk mitotic rate, pushing margin, and the presence of geographic necrosis/central fibrosis were all significantly more common in ER- than in ER+ tumors. Conclusions: To our knowledge, this study is the first to document in detail the histologic features of the uncommon ER+ IBC occurring in BRCA1 mutation carriers. Our observations suggest that ER+ IBC in BRCA1 mutation carriers represent a morphologically diverse group. This raises the possibility that at least some ER+ IBC that develop in women with germline BRCA1 mutations may be sporadic rather than BRCA1 -associated. We are currently analyzing these lesions with a panel of biomarkers and assays for loss of heterozygosity at the BRCA1 mutation sites to further address this important issue. This work was supported by a grant from the Breast Cancer Research Foundation. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1105. [1]: /embed/graphic-1.gif