Prevalence of BRCA1 mutations among 284 women with triple-negative breast cancer.

Abstract

1511 Background: Triple-negative breast cancer (TNBC) is a type of aggressive breast cancer diagnosed in approximately 15% of total breast cancer patients. TNBCs are characterised by the lack of expression of estrogen receptors alpha (ER-α), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2), and thus are unresponsive to currently available ER-targeted and HER2-based treatments. An intriguing characteristic of TNBC is its association with hereditary breast cancers, as TNBCs are over-represented in BRCA1 mutation carriers. The etiology behind this association is yet unclear but may ultimately provide avenues for prevention and targeted therapy. Screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of hereditary breast cancer. Genetic testing is offered to a breast cancer patient usually according to her family history; however some women may qualify for testing solely because of an early age of onset and/or tumor pathology, such as the triple-negative phenotype. There is a lack of population studies that determine the frequency of BRCA1 mutations among TNBC patients. Methods: We studied 284 women who were diagnosed with triple-negative invasive breast cancer independently of their age or family history. The mean age for the total cohort was 50.4 years (range: 21-76). The most prevalent BRCA1 mutations in the Greek population that account for 54% of all mutations detected in both genes (BRCA1 and BRCA2), were screened in all patients. Additionally, BRCA1 exons 5, 11 and 23 were also sequenced in cases with age of onset < 40 years. Results: Thirty deleterious BRCA1 mutations were identified in the 284 patients with triple-negative breast cancer (10.6%). Mean age of onset for all mutation carriers was 40.2 years (range: 28-57). Of the 30 carriers, 10 had no reported family history of breast or ovarian cancer. Among a total of 36 women with early-onset TNBC (< 40 years), 17 (47%) had a BRCA1 mutation. Conclusions: Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer. No significant financial relationships to disclose.