Most patients with triple-negative breast cancer should undergo genetic testing for mutations in known breast cancer genes, including BRCA1 and BRCA2, according to the largest analysis to date of genetic mutations in TNBC, published in the Journal of Clinical Oncology.
The study found that almost 15 percent of triple-negative breast cancer patients had harmful mutations in breast cancer-related genes. The vast majority of these mutations appeared in genes involved in the repair of DNA damage, suggesting that the origins of triple-negative breast cancer may be different from other forms of the disease. The study also provides evidence in support of the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing of triple-negative breast cancer patients.
Recent studies have suggested that triple-negative breast cancer patients might harbor genetic mutations that make them more likely to respond to alternative treatments like cisplatin, a chemotherapy agent, or PARP inhibitors, anti-cancer agents that inhibit the poly (ADP-ribose) polymerase (PARP) family of enzymes.
In the current study, researchers sequenced DNA from 1,824 triple-negative breast cancer cases seen at 12 oncology clinics in the U.S. and Europe, as part of the Triple-Negative Breast Cancer Consortium.They found dangerous mutations in almost 15 percent of triple-negative breast cancer patients. Of these, 11 percent had mutations in the BRCA1 and BRCA2 genes and the rest had mutations in 15 other predisposition genes, including the DNA repair genes PALB2, BARD1, and RAD51C. No mutations were found in predisposition genes involved in other processes like the cell cycle.
The study also found that individuals with mutations in predisposition genes were diagnosed at an earlier age and had higher-grade tumors than those without mutations. The researchers used their dataset to assess whether the current screening guidelines would identify all the triple-negative individuals with mutations in the two most common predisposition genes, BRCA1 and BRCA2.
They found that the NCCN guidelines, which recommend screening when there is a family history of cancer or a diagnosis under age 60, missed only 1 percent of patients carrying mutations. In contrast, the UK’s National Institute for Clinical Excellence (NICE) guidelines, which use the probability of actually finding a mutation to determine who should be tested, missed 24 percent of mutation carriers. They suggested expanding the NICE guidelines for TNBC patients.