Three decades ago, African-American women and American women of European descent experienced similar rates of death from breast cancer. Since then, mortality rates among the two groups have diverged. The most recent numbers from the US National Cancer Institute indicate that the mortality rate from breast cancer among African-American women is about 28 per 100,000, as compared to 20 per 100,000 among US women of European descent. This difference might partially stem from the fact that new treatments do not always work against the most aggressive breast cancer subtypes, which are more common in the former group than in the latter. But this disparity in cancer-treatment options does not necessarily explain all of the difference between the current mortality rates.

To probe for genetic risk factors that might contribute to the higher prevalence of aggressive and difficult-to-treat tumors in African-American women, in July, the US National Institutes of Health announced that it would fund a new consortium. With the support of a $12-million grant from the agency, the consortium will conduct the largest genetic analysis so far of blood, saliva and breast cancer tissue samples from this patient group. Called the Breast Cancer Genetic Study in African-Ancestry Populations, the project will perform detailed genetic analyses of these tissues, pooled from 18 study cohorts in total. With samples from a total of 20,000 women with breast cancer and 20,000 controls without the disease, it will be more than five times the size of the biggest previous data-sharing partnerships for genetic studies of breast cancer in African-American women. Earlier studies have been too small, and thus statistically too weak, to detect genetic variants that subtly increase breast cancer risk, including most risk variants identified in statistically more powerful genome-wide association studies of women of European and Asian descent. Because many African-American women are not solely of African descent, the new consortium-led study will include data on genetic markers of ancestry. These will enable scientists to use an individual's percentage of African ancestry as a variable in the analysis.

The study will begin with next-generation sequencing of the entire genomes—including noncoding regions—of blood from 1,200 women with breast cancer and 600 healthy controls chosen from cohort studies that contain the best-quality data and samples. Wei Zheng, a cancer epidemiologist at Vanderbilt University and co-investigator of the consortium, hopes to find novel genetic risk variants that might lend themselves to clinical-screening tests or suggest new treatment targets. He and his colleagues will select the most promising genetic variants from this first cohort and look for them in the rest of the samples in the consortium to validate their findings independently.

Vicious variants: Genes influence cancer (pictured). Credit: Photo Researchers, Inc/Alamy Stock Photo

To find genetic risk variants associated with estrogen-receptor-negative breast cancer, the scientists have chosen samples from women with this cancer subtype to make up half of the 1,200 genomes of affected individuals that they plan to sequence completely. 'Triple-negative' tumors, which lack hormone receptors or the growth-promoting HER2 protein on their cell surfaces, occur at a rate of 27 per 100,000 among African-American women—nearly twice the rate for US women of European descent (J. Natl. Cancer Inst. 107, djv048, 2015). This aggressive subtype does not respond to endocrine therapies, such as tamoxifen, or therapies that target HER2. Even outside the US, women of African ancestry have high rates of triple-negative breast cancers, as compared to women of European ancestry (Lancet Oncol. 15, e625–e634, 2014). The greater rate of these cancers in African-American women “definitely plays a role” in the group's higher mortality rate from breast cancer, says Lisa Newman, an oncologist at the University of Michigan.

Still, trying to connect genetic factors with health disparities defined by race is problematic, says Dorothy Roberts, a sociologist at the University of Pennsylvania Law School. “It assumes that African-American women have a peculiar biology that is distinct from the biology of women of other races, and that's not true,” she says. “We should be moving toward research that eliminates the idea that human beings are in biologically distinct races.”

“The answer to health disparities will never be in our genes,” says Alexandra Shields, director of the Harvard–MGH Center on Genomics, Vulnerable Populations, and Health Disparities. Social and environmental factors from structural inequalities are more likely to drive disparities in the rates of breast cancer mortality, she says.

Researchers involved in the new consortium are well aware that genetic studies cannot sufficiently explain the racial disparity in breast cancer mortality. Damali Martin, an epidemiologist at the National Cancer Institute, agrees that social factors such as neighborhood conditions are driving the disparity, but says that genetic factors might also contribute. “Once we've obtained information on genetic risk variants, in combination with environmental risk variants, we can try to understand how all of these work together to cause worse outcomes for breast cancer in African-American women,” she says.

Shawneequa Callier, a bioethicist at George Washington University, applauds the attention given to women previously neglected in genetic research, but notes that learning about breast cancer in African-American women will be only a part of improving medical care. “If we're going to enroll people of color in studies, what will we do to ensure access to care when that knowledge becomes available?”