BRCA1/2 and Other Breast Cancer Gene Mutations in Patients Unselected for Family History
How frequent are mutations in known breast cancer predisposition genes in women with TNBC who were unselected for family history?
Overall, between 12% and 15% of breast cancers are triple-negative breast tumors (TNBC), which are most common in younger, premenopausal women and African Americans and refractory to treatments, such as herceptin, that have improved breast cancer outcomes for many women.
In series of unselected TNBC patients, approximately 10% are associated with BRCA1 germline mutations, leading the National Comprehensive Cancer Network (NCCN) to recommend BRCA1/2 testing when TNBC is diagnosed in women younger than age 60.1,2
The availability of options that decrease risk and improve mortality in BRCA1/2-positive cancers makes identification of the best candidates for genetic testing of great importance to optimal care.
A new study led by Fergus J. Couch, PhD, of the Mayo Clinic in Rochester, MN, and published in the Journal of Clinical Oncology, examined the frequency of mutations in known breast cancer predisposition genes in a multinational cohort of 1,824 women with TNBC who were unselected for family history.
Across the entire cohort, 14.6% of women at least 1 deleterious mutation, predominantly BRCA1, identified in 8.5% (155 patients), and BRCA2, identified in 2.7% (49 patients). As expected, family histories of breast (BRCA1) or ovarian (BRCA1 and BRCA2) cancer were strongly associated with BRCA1/2 mutations (all, P<0.001).
However, substantial proportions of women who tested positive for BRCA1/2 had no family history of disease. The presence of BRCA1/2 in women without family history was strongly associated with younger age: only 1.4% of women age 60 or older with no family history had BRCA1/2 mutations, compared with 7.5% of women age 50 to 59, 8.6% of women age 40 to 49, 15.4% of women age 35 to 39, and 19.8% of women younger than 35.2