Even Those With Susceptibility Genes Can Lower Breast Cancer Risk

People who carry a germline breast cancer susceptibility mutation can still substantially lower their risk of developing breast cancer, according to a new study.

People who carry a germline breast cancer susceptibility mutation can still substantially lower their risk of developing breast cancer, according to a new model published in JAMA Oncology.

The model of risk stratification suggests that genetics do not solely predict a breast cancer fate. According to the authors led by Paige Maas, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute in Bethesda, Maryland, this type of model could improve public health strategies for breast cancer prevention.

The researchers found that 28.9% of breast cancer cases among white women, including those with a family history of the disease and genetic risk, could be prevented if women adopt a healthy lifestyle by avoiding smoking, drinking very little alcohol, keeping a stable, healthy body weight, and opting out of hormone replacement therapy.

Besides mutations in BRCA1 and BRCA2, there are about 92 other mutations that have been linked to an increased risk of breast cancer. While these single nucleotide polymorphisms (SNPs) are each associated with only a small effect size, they can cumulatively explain substantial variation in risk.

Using 17,171 cases and 19,862 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3), as well as 5,879 women participating in the 2010 National Health Interview Survey, the researchers compiled individual data of epidemiologic risk factors to build a model of absolute breast cancer risk. The model also included 24 genotyped SNPs from prospective cohort studies, published estimate of odds ratios for 68 additional SNPs, and incidence rates and distribution of risk factors in the United States among white women.

The average chance of a 30-year-old white woman being diagnosed with breast cancer before age 80 is about 11%. Maas and colleagues found that white women at high risk for the disease who had a low body mass index and who did not drink or smoke and did not use hormone replacement therapy, had about the same risk as an average white women in the United States.

“People think that their genetic risk for developing cancer is set in stone,” said study author Nilanjan Chatterjee, PhD, of the department of biostatistics at the Bloomberg School of Public Health at Johns Hopkins University, in a statement. “While you can’t change your genes, this study tells us even people who are at high genetic risk can change their health outlook by making better lifestyle choices such as eating right, exercising, and quitting smoking.”

Still, the model thus far is only for those with an increased risk of breast cancer due to a genetic mutation.

The study points to a potential strategy for screening stratification. Older age is the most important risk factor for developing breast cancer. According to the model, about 16% of 40-year-old women have the same risk as an average 50-year-old woman, suggesting that some women may need to undergo screening starting at an earlier age.

With about 245,000 new cases of breast cancer diagnosed in the United States in 2016 and 40,000 women who die of the disease annually, the model provides a way forward to combine genetics and lifestyle information to inform breast cancer prevention strategies.