Of additional interest, this study used multigene testing and discovered 15 other genetic mutations that were present to varying degrees in 3.7% of the women. The most frequent (after BRCA1/2) were mutations in PALB2, found in 21 patients (1.2%).
Other mutations found in more than 2 women included BARD1 (9 patients), BRIP1 (8 patients), RAD51D (7 patients), RAD50 (6 patients), RAD51C (6 patients), and XRCC2 (2 patients). Many of these genes are involved in homologous recombination repair, suggesting that disruption of that process may be implicated in development of TNBC.2
Overall, 38% of mutations were found in women younger than age 40, and presence of any mutation was associated with diagnosis at a significantly younger ages (from 4 to 8 years depending on the mutation) than a TNBC diagnosis with wild-type genes.2
The data from this large series of women with TNBC demonstrate that a substantial proportion of women who develop TNBC prior to age 60 harbor mutations in BRCA1/2.
Because many women do not recognize aspects of their family history, especially when breast or ovarian cancer may have occurred in their father’s family, these results give added relevance to NCCN guidelines recommending BRCA1/2 testing when TNBC is diagnosed in women younger than age 60, regardless of family history.
Whether testing for other mutations using multigene panels has clinical relevance for breast cancer treatment and outcomes is a question that requires further research.1
- Domchek SM. Evolution of genetic testing for inherited susceptibility to breast cancer. J Clin Oncol. December 15, 2014. doi:10.1200/JCO.2014.59.3178. [Epub ahead of print]
- Couch FJ, Hart SN, Sharma P, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. December 1, 2014. doi:10.1200/JCO.2014.57.1414. [Epub ahead of print]