BRCA1a has antitumor activity in triple-negative breast cancers

Most BRCA1-related breast cancers are high-grade, basal-like, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and Her2-negative. Triple-negative breast cancers are more common in younger black women than their white counterparts, have higher rates of distant metastasis, and currently there are no effective treatments against these cancers. We have previously characterized a splice variant of BRCA1 (BRCA1a/p110), which is expressed at reduced levels in several breast tumors. Stable expression of BRCA1a resulted in inhibition of growth in vitro of human breast, ovarian, prostate and colon cancer cells, and only those cells with wild-type Rb were sensitive to BRCA1a-induced growth suppression and the status of p53 did not affect the ability of BRCA1a to suppress growth of tumor cells. We have introduced BRCA1a into the CAL51 cell line, which is negative for ER and PR, and our results using semiquantitative immunocytochemistry show CAL51 to be negative for HER2. These transfectants were analyzed for BRCA1a protein expression by western blot analysis. The BRCA1a transfectants were slow growing and 98% inhibited in their growth in soft agar. BRCA1a also significantly inhibited CAL-51 triple-negative breast cancer xenografts in nude mice. These results suggest that the majority of exon 11 sequences lost in BRCA1a are not required for the tumor suppressor function. This is the first report showing antitumor activity of BRCA1a in triple-negative breast cancers.