Mechanism of ER-Negative Breast Cancer in BRCA1-Mutation Carriers

BRCA1 protein directly regulates the estrogen-receptor α gene by binding to its promoter.

Germ-line mutations in the BRCA1 tumor-suppressor gene confer a substantial genetic predisposition for breast and ovarian cancers in carriers. BRCA1-mutant breast tumors tend to be associated with the estrogen-receptor (ER)α-negative, basal subtype of breast cancer (so-called “triple-negative” tumors), in contrast to most sporadic breast cancers that express wild-type BRCA1 and are ERα-positive. The BRCA1 mutation is particularly prevalent in certain ethnic populations, such as Ashkenazi Jews.

BRCA1 inhibits ERα signaling, which results in inhibition of downstream gene expression. Earlier work has suggested a direct connection between BRCA1 expression and ERα function (Endocr Relat Cancer 2005; 12:533). Transient transfection of the BRCA1 ge…

Reviewing Author

William J. Gradishar, MD

Disclosures

Consultant/Advisory BoardLilly; AstraZeneca; Gilead

Grant/Research SupportBreast Cancer Research Foundation

Editorial BoardsClinical Breast Cancer; Oncology; Annals of Surgery; Breast Cancer Research and Treatment

Leadership Positions in Professional SocietiesNational Comprehensive Cancer Network (Chair, Breast Cancer Panel); American Board of Internal Medicine (Medical Oncology Board)