For decades, the only genes tested for breast cancer risk were BRCA1 and BRCA2. Advances in genetic testing for hereditary cancer risk now enable clinicians to use multiple-gene panels to identify mutations. These panels have identified mutations in other cancer-associated genes in 5% to 15% of BRCA1/2-negative patients with suspected hereditary breast and ovarian cancer (HBOC) syndrome—more than doubling the mutation detection rate.
Researchers analyzed data from a commercial laboratory database of 95,561 women tested clinically for hereditary cancer risk with a 25-gene, next-generation sequencing panel. They accounted for family history and examined the association between pathogenic mutations and breast or ovarian cancer. A matched case-control analysis was conducted, defining cases as patients with breast or ovarian cancer and controls as women without cancer.
One or more pathogenic mutations were detected in 6775 (7%) of 95,561 women. Eight genes (ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, PTEN, and TP53) were associated with breast cancer, with odds ratios ranging from two-fold to six-fold.
Eleven genes (ATM, BRCA1, BRCA2, BRIP1, MLH1, MSH2, MSH6, NBN, STK11, RAD51C, and RAD51D) were associated with ovarian cancer, with odds ratios ranging from two-fold to 40-fold. The researchers concluded that among the 95,561 women studied, 7% carried a pathogenic mutation in one or more cancer-associated genes. Associated breast and ovarian cancer risks ranged from two- to 40-fold after controlling for family history. They note that these results may better inform cancer risk counseling. The study findings are available here.