Histologic and Immunophenotypic Comparison of Estrogen Receptor (ER)-Positive Breast Cancers in BRCA1 Mutation Carriers and Sporadic ER-Positive Breast Cancers: A Case-Control Study
J Kaplan, S Schnitt, L Collins, Y Wang, J Garber, K Montgomery, R West, N Tung. Beth Israel Deaconess Medical Center, Boston, MA; Dana Farber Cancer Institute, Boston, MA; Harvard Medical School, Boston, MA; Stanford University, Palo Alto, CA
Background: Most invasive breast cancers (IBC) in BRCA1 mutation carriers are ER negative (-). These tumors are most often high grade invasive ductal carcinomas and have a basal-like phenotype. However, up to one-third of BRCA1-associated IBC are ER positive (+). We previously reported that ER+ BRCA1-associated IBC show a wider spectrum of histologic types and grades than ER- IBC that occur in this setting, raising the possibility that at least some of these ER+ IBC may be sporadic rather than mutation-related. However, how the features of ER+ BRCA1-related IBC compare directly to sporadic ER+ IBC has not been previously studied.
Design: We performed a case-control study of 60 ER+ IBC arising in women with BRCA1 germline mutations (cases) matched on age and year of diagnosis with 174 ER+ sporadic breast cancers (controls). Histologic features were reviewed and tissue microarrays (TMAs) were constructed and immunostained for CK5/6, CK7/8, CK14, CK18, CK19, EGFR, and HER2. Immunostain results were analyzed by unsupervised hierarchical clustering using Cluster and Treeview programs.
Results: ER+ BRCA1-associated IBC were significantly more likely than sporadic ER+ IBC to be invasive ductal type (p=0.005), histologic grade 3 (p=0.006) and to have a high mitotic rate (p=0.0003). In addition, ER+ BRCA1-associated IBC were 4-times more likely to express basal cytokeratin CK14 than ER+ sporadic IBC (13% versus 3%, respectively, p = 0.02). On unsupervised cluster analysis, ER+ BRCA1-associated IBC were heterogeneous with regard to their biomarker expression profile; some clustered more closely with sporadic ER+ IBC whereas others clustered more closely with ER- BRCA1-associated IBC.
Conclusions: The results of this study show for the first time that ER+ breast cancers arising in women with BRCA1 germline mutations show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers. This raises the possibility that some ER+ BRCA1-associated invasive breast cancers are mutation-related and others are sporadic or that there is a unique mechanism by which ER+ cancers develop in mutation carriers. Additional immunophenotypic and molecular studies are underway to further characterize this group of tumors.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 22, Monday Morning