In the study, 15-16 percent of patients with triple-negative breast cancer, one of the most aggressive forms of the disease, were found to have genetic mutations, including BRCA 1 and BRCA 2, that predispose them to breast cancer. In breast cancer patients overall, that figure is much lower—only 5 percent of women have risk-elevated mutations.
The study also found that the breast cancers in women with mutations in predisposition genes emerged at an earlier age and had higher-grade tumors than in those without mutations.
Based on these findings, Dr. Couch and his team decided to study whether current guidelines for determining which women should be tested for genetic mutations were appropriate. In the United States, the National Comprehensive Cancer Network (NCCN) recommends screening for triple negative breast cancer patients when there’s a family history or a diagnosis under 60 years old. While NCCN guidelines work well here in the U.S., missing only 1 percent of patients carrying mutations, guidelines in other countries miss a significant number of mutation carriers. With his research, Dr. Couch is hoping to demonstrate the importance of genetic testing to ensure women around the world are fully informed about their risk.
BCRF: Why does triple negative breast cancer have a higher rate of genetic mutations compared to other types?
Dr. Couch: We think of triple negative breast cancer as having a defect in DNA repair, and our data suggests that’s true. DNA repair gene mutations are more frequent in triple negative disease, which goes along with what we know about BRCA1 and BRCA2 mutations contributing to a higher risk of breast cancer. Our findings generate a whole new set of hypotheses about how triple negative breast cancer might be arising, which could give us better ideas for prevention or new therapies.
BCRF: What does discovering that triple negative breast cancer has a higher incidence of genetic mutations mean for treatment and prevention?
Dr. Couch: The women we screened have already developed their cancers, but there may be specific therapeutic benefits. For instance, some studies suggest that women with triple negative breast cancer and gene mutations are more likely to respond to alternative treatments like PARP inhibitors or Cisplatin. There’s also an increased risk of recurrence among these women.
Additionally, it’s valuable for family members to learn of these mutations since it affects their risk of breast, ovarian and other cancers.
BCRF: What are your recommendations on genetic screening for women who have a high risk of getting breast cancer but don’t yet have the disease?
Dr. Couch: We recommend that all women and men with triple negative breast cancer receive genetic screening and counseling. While the NCCN guidelines have been around for some time now, doctors haven’t always used them because the benefit for the patient was not always clear. Our study suggests that screening will be important for choosing effective therapies, predicting risk of future cancers, and benefits to family members.
BCRF: Your findings were more or less in line with what’s already in place for the U.S., but what does this mean for other countries? What implications do you see your study having for testing guidelines globally?
Dr. Couch: In the United Kingdom, the National Institute for Health and Care Excellence (NICE) guidelines are based on a cost-benefit model. They will test if they can look at a patient’s family history and determine that the probability of a mutation is greater than 10 percent. The problem is that those guidelines miss about 16 percent of mutation carriers, which has major implications for treatment options, and for cancer risks among other family members. We think the NICE guidelines could be expanded to include more of the triple-negative breast cancer patients with mutations.