Goldberg Family Foundation advances research on inherited breast cancer risk

For people who inherit mutations in the BRCA1 gene, the increased risk of breast cancer can mean making extraordinarily difficult choices, including surgery to remove healthy breast tissue. Evan M. Goldberg, AB ’87, and Cindy Goldberg hope research can offer less invasive options for those at elevated risk.

Their recent $1.06 million gift through the Goldberg Family Foundation supports a collaboration between Joan Brugge, PhD, the Louise Foote Pfeiffer Professor of Cell Biology in the Blavatnik Institute at Harvard Medical School and co-director of the Ludwig Center at Harvard, and Eliezer Mendel Van Allen, MD, an HMS professor of medicine at Dana-Farber Cancer Institute (DFCI). The gift builds on the Goldbergs’ long-standing support for collaborative BRCA research between HMS and DFCI.

BRCA1 normally helps to repair damaged DNA and suppress the development of cancer. Mutations in this gene can impair its protective function, increasing the risk of several cancers. Brugge and Van Allen are focused specifically on developing targeted, less invasive strategies to intervene in breast cancer before it takes hold.

According to the National Cancer Institute, more than 60% of women who inherit a mutation in BRCA1 or BRCA2 will develop breast cancer during their lifetime. By contrast, about 13% of women in the general population will develop breast cancer during their lifetime.

Their project builds on evidence suggesting that an increase in the number of copies of 1q—a section of chromosome 1—may be one of the earliest changes that enables breast cells with BRCA1 mutations to progress toward cancer. The team will combine laboratory experiments with genomics, computational analysis, and artificial intelligence to identify the genes and cellular programs that help these cells survive after BRCA1 function is lost and set the stage for tumor formation.

Learn how Joan Brugge’s professional fight against cancer began 

“Just as cancer treatment often requires a combination of therapies, groundbreaking cancer research often requires a combination of skills and expertise,” says Evan Goldberg. “Bringing these two incredible researchers together to marry the science with advanced computational tools is an especially powerful combination.”

The project will draw on the Gray BRCA Pre-Cancer Atlas, which contains breast tissue samples from women with mutations in BRCA1 or the related BRCA2 gene, as well as from women without mutations in either gene. These samples will allow researchers to compare individual cells and examine how their genetic activity changes as they move toward cancer. The team will use CRISPR gene-editing screens to test candidate genes, then evaluate promising targets in organoids and mouse models that mimic the earliest stages of BRCA1-related breast cancer.

The researchers will also investigate +1q aneuploidy, an abnormal gain of genetic material on chromosome arm 1q. Understanding how this change affects breast tissue with BRCA1 mutations could reveal why some cells progress toward cancer and identify vulnerabilities that can be targeted. As Brugge explains, “These studies will set the stage for a much larger, highly ambitious, and interdisciplinary project at the interface of cancer development and AI, with emphasis on BRCA1 and BRCA2 carriers and studying the origins of this disease toward devising novel strategies for prevention.”

Goldberg says that a better understanding of how cancer develops from inherited mutations will help these and other cancer researchers know where to focus their work and “move us down the road to the ultimate destination—where individuals affected by familial cancer, including those in BRCA families, are freed from the invasive preventative measures they must take now.”