BRCA2, a gene associated with increased risks of breast cancer, can be mutated in thousands of ways—but only some of those mutations are dangerous. The key question for oncologists, genetic counselors, and women with breast cancer is: which ones?
Ryan B. Jensen, Ph.D., associate professor of therapeutic radiology, is sorting through thousands of BRCA2 mutations to spot the red flags. His work could greatly improve counseling and cancer treatment for breast cancer patients.
Jensen is moving his research forward in part thanks to a grant from Women’s Health Research at Yale (WHRY), a self-supporting center within Yale School of Medicine that will celebrate its 20th anniversary in February. With data developed through $5 million in WHRY grants to date, Yale scientists have gone on to secure $95 million in external grants to further their research into women’s health.
“Women continue to be underserved in terms of research knowledge,” says Carolyn M. Mazure, Ph.D., the Norma Weinberg Spungen and Joan Lebson Bildner Professor of Psychiatry and Psychology, who founded the center in 1998 and has been executive director ever since.
The center focuses on the need to fully account for sex and gender in biomedical research. Women suffer higher rates of Alzheimer’s disease, for instance, and can present with different symptoms than men when experiencing heart attacks. But studies of these diseases traditionally pay inadequate attention to sex differences, Mazure says.
It was not until 1994 that the National Institutes of Health (NIH) required researchers to include women participants in clinical studies and to analyze data by sex or gender. It was not until last year that the NIH required female animals and tissue and cell samples in laboratory studies. To this day, many studies are still not designed to tease out sex differences.
WHRY-funded research, though, has already helped women and girls.
In 2002, for example, a landmark paper published in The Lancet led to better advice for breast cancer patients and those at higher risk for breast cancer. WHRY grant recipient Bruce G. Haffty, M.D., then of the Department of Therapeutic Radiology, showed that certain mutations in the genes BRCA1 and BRCA2 predisposed breast cancer patients to new tumors in either breast.
Girls with autism also stand to benefit from the center’s grants. Because boys outnumber girls in autism diagnoses, many studies include few if any girls.
“They’ve been orphaned from autism research,” says Pamela Ventola, Ph.D., assistant professor in the Yale Child Study Center.
With a 2015 WHRY grant, Ventola tested for the first time a behavioral intervention called Pivotal Response Therapy on girls with autism. The girls made bigger gains in social engagement and functioning than boys in the study—despite having started with more severe impairments.
“Without these pilot data, girls would still be under-studied,” Ventola says. “We are extremely grateful for the funding from WHRY. Without the work supported through this grant, we wouldn’t know the value of this therapy in girls.”
Jensen, too, says the funds were crucial to his work. When he arrived at Yale as a junior faculty member, he had recently made a crucial breakthrough, becoming the first in the world to purify the BRCA2 protein. But there was no way to follow up without seed money that would let him establish the preliminary data necessary for the larger NIH grants he later received and that continue to fund his work today.
“The pilot grants are great for young investigators—I got this within a year of when I came to Yale,” he says. “It gives you practice writing grants at this level, and then you get some feedback. It really helps you start preparing for the big NIH grants. And it keeps your lab going.”
WHRY-funded researchers at Yale study colon cancer and autoimmune disease in women, as well as ovarian cancer, infections during pregnancy, intimate partner violence, and other topics to advance women’s health or discover sex differences to benefit women and men.
Mazure advocates for women’s health research in Washington, D.C., and has frequently spoken at other universities about how they might build programs similar to Yale’s and fully integrate a focus on sex and gender into a medical school curriculum.
“We have been enthusiastic about helping others to build these centers,” says Mazure. “We want more people focusing on the importance of studying women and investigating sex and gender differences. It is vital to help women, and it can also help men. Because in studying differences, we learn things that are very important for the care and treatment of disorders that affect us all.”
Looking back over nearly 20 years, Mazure is quick to turn her attention toward the road that lies ahead. “We have made great progress,” she says. “But there is an enormous amount left to do.”