Original ArticlesPathologic Features and Immunophenotype of Estrogen Receptor–positive Breast Cancers in BRCA1 Mutation CarriersKaplan, Jennifer S. MD*,†; Schnitt, Stuart J. MD*,†; Collins, Laura C. MD*,†; Wang, Yihong MD, PhD*,†; Garber, Judy E. MD†,‡; Montgomery, Kelli BA§; West, Robert B. MD, PhD§; Krag, Karen MD∥; Fetten, Katharina MA¶; Lincoln, Anne MS¶; Tung, Nadine M. MD†,¶Author Information *Department of Pathology ¶Division of Hematology/Oncology, Beth Israel Deaconess Medical Center ‡Division of Population Sciences and Adult Oncology, Dana Farber Cancer Institute †Harvard Medical School, Boston ∥Program in Oncology, North Shore Medical Center, Danvers, MA §Department of Pathology, Stanford University Medical School, Stanford, CA Conflicts of Interest and Source of Funding: Supported in part by a grant from the Breast Cancer Research Foundation to S.J.S. and N.M.T. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Stuart J. Schnitt, MD, Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215 (e-mail: [email protected]). The American Journal of Surgical Pathology: October 2012 - Volume 36 - Issue 10 - p 1483-1488 doi: 10.1097/PAS.0b013e31825789ed Buy Metrics Abstract Although most breast cancers in BRCA1 mutation carriers are estrogen receptor negative (ER−) with a basal-like phenotype, up to one third are ER positive (ER+). Little is known about the characteristics of this subgroup. To address this, we compared histologic and immunophenotypic features of 60 BRCA1-related ER+ breast cancers with those of 85 BRCA1-related ER− cancers and 174 matched ER+ sporadic cancers. ER+ BRCA1–related cancers were significantly less likely than ER− BRCA1–related cancers to be of pure invasive ductal type (P<0.001) and to be of histologic grade 3 (P<0.001), and less frequently to have a high mitotic rate (P<0.001), pushing (or unknown) margins (P<0.001), a moderate/marked lymphocytic infiltrate (P=0.003), or geographic necrosis/fibrotic focus (P<0.001). In addition, ER+ BRCA1–related cancers less often expressed CK5/6 (P<0.0001), CK14 (P<0.0001), and epidermal growth factor receptor (P<0.0001) and more often expressed progesterone receptor (P<0.0001). In contrast, when compared with ER+ sporadic cancers, ER+ BRCA1–related cancers were significantly more often of invasive ductal type (P=0.005) and of histologic grade 3 (P=0.006), more frequently had a high mitotic rate (P=0.0003), and were more often CK14+ (P=0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more closely with sporadic ER+ cancers, whereas others clustered more closely with ER− BRCA1–related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1 in ER+ BRCA1–related cancers were similar to those in ER− BRCA1–related cancers but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1–related breast cancers show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers as well as some similarities to ER− BRCA1–related cancers. © 2012 Lippincott Williams & Wilkins, Inc.