Eureka!

It’s in the Genes

A breast cancer survivor’s hunch leads to a game-changing study

Illustration by Sandra Dionisi

By Patricia Donovan

In 2007, Veronica Meadows-Ray of Buffalo became the sixth of eight women in her family to be diagnosed with breast cancer.

In her case, it was triple negative breast cancer, an aggressive and frequently recurring type that is most likely to occur before the age of 50, in African-American and Hispanic women, and in women who carry a mutation of the tumor-suppressor gene BRCA1. Meadows-Ray met the first two of those criteria—she is African-American and was 47 when diagnosed—but she tested negative for the BRCA gene. Her one cousin who also underwent genetic screening also tested negative.

“It seemed unlikely that coincidence alone would produce seven cases of breast cancer in two generations,” Meadows-Ray says. “I just felt that something else, maybe an unknown genetic mutation, might be affecting my family.”

Meadows-Ray (left) and Ochs-Balcom (PhD ’04). Photo: Douglas Levere

There were no answers to her questions, however. The pioneering BRCA study, conducted in the 1990s, had found that mutations in the BRCA1 and 2 genes accounted for 20 to 25 percent of hereditary breast cancers, and 5 to 10 percent of all breast cancers, in the study population—but that population was composed of 5,000 women of European heritage. No one had ever conducted a genetic study of breast cancer in African-American families, despite the fact that African-American women have the second-highest incidence of breast cancer in the United States, and the highest rates of mortality from the disease.

Meadows-Ray is active in the Buffalo/Niagara Witness Project, one of more than 30 programs nationwide that work to educate African-American women about early detection for breast cancer. She took her questions to Witness Project co-founder Deborah Erwin, director of the Office of Cancer Health Disparities Research in the Division of Cancer Prevention and Population Sciences at Roswell Park Cancer Institute (RPCI). Citing her family’s breast cancer history, Meadows-Ray proposed a study that would look for new genetic mutations related to breast cancer common in, or even unique to, African-American families.

Erwin proposed the idea to genetic epidemiologist Heather Ochs-Balcom of the UB School of Public Health and Health Professions, and Ochs-Balcom (PhD ’04) turned it into “Jewels in Our Genes,” a nationwide research project conducted between 2009 and 2014. Led by Ochs-Balcom and funded by Susan G. Komen for the Cure, the study involved 106 families from across the U.S. and researchers from UB’s school of public health, Roswell Park, Case Western Reserve University School of Medicine in Cleveland, and the Icahn School of Medicine at Mount Sinai Hospital in New York.

The team recently announced its first discovery: Study participants with breast cancer carry segments of DNA that were previously unknown and that are not carried by their female relatives who don’t have breast cancer.

“This is a very exciting finding,” says Ochs-Balcom, who published the results in the journal Cancer Epidemiology, Biomarkers & Prevention in February. “Now that we’ve found the new genomic regions, we can search them for chromosomal mutations that cause the disease and try to learn if the mutations are unique to African-Americans.”

Ochs-Balcom points out that young African-American women are at higher risk of premenopausal breast cancers than others in their age group. Early-onset cancers and aggressive, difficult-to-treat cancers (like triple negative) are also much more common in African- American women than in other groups. If a genetic mutation is responsible, its discovery would facilitate early detection and treatment for women in at-risk families, which would go a long way toward improving outcomes for those with the gene.

Part of the reason this research hasn’t been done until now, says Ochs-Balcom, is that family studies—the best way to discover genetic anomalies—are difficult; they require a considerable time commitment by multiple family members. This study was made possible by a multipronged recruitment approach involving informed, supportive community partners.

“Across the country, community organizations and individuals like Veronica personally encouraged friends, neighbors and family members to take part,” Ochs-Balcom says, adding that volunteers were especially good at conveying the urgency and importance of this work. Indeed, this community recruitment methodology was so successful, it was presented at the 2014 annual meeting of the American Association for Cancer Research.

Ochs-Balcom says she cannot stress enough the critical role played by Meadows-Ray in making this paradigm-shifting research happen. “Whatever success we realize,” she says, “I want to emphasize that this study—the first of its kind—started with her.”