Mutations commonly linked to breast cancer found to pose no increased risk

Several genetic mutations previously linked to breast cancer and included on commercial genetic tests, including direct-to-consumer tests, were found not to increase a woman’s risk of disease, according to a population study of more than 64,000 women published in the New England Journal of Medicine from several institutions, including Penn Medicine. The findings show that risks associated with mutations for women in the general population are often lower than previous estimates, and, importantly, provide new insights informing the debate over whom should be recommended for genetic testing.

Gloved hands putting individual tiny pipettes in a holder in a lab setting.

Penn Medicine authors on the paper—which analyzed data from the CARRIERS study, or “CAnceR RIsk Estimates Related to Susceptibility”—include Katherine L. Nathanson, deputy director of the Abramson Cancer Center and the Pearl Basser Professor for BRCA-Related Research in the Perelman School of Medicine and Susan M. Domchek, executive director of the Basser Center for BRCA at the Abramson Cancer Center.

According to past estimates, seven to 10% of women with breast cancer carry variants in genes associated with an increased risk. However, that statistic is based largely on studies of high-risk women, including those with a family history or a young age of cancer diagnosis.

This study—the first to look at a large group of women of different ages from the general population—suggests that the frequency of these variants in genes associated with breast cancer risk among women in the general population is 5%. Further, of the 28 breast cancer genes studied, only 12 had clear evidence of associated cancer risk.

“These findings have important implications for the clinical management of patients,” Nathanson says. “This study has a more accurate risk estimate for the overall breast cancer population, as opposed to selected high-risk patients, that we believe will inform ongoing and future discussions around genetic testing for women and other risk management strategies.”

Read more at Penn Medicine News.