Why cancers caused by BRCA mutations recur

Findings from Penn Medicine uncover possible drivers of recurrent breast and ovarian cancers among women carrying high-risk genetic mutations, pointing to methods to more effectively treat disease.

Researchers at Penn’s Basser Center for BRCA at the Abramson Cancer Center have discovered factors that may make breast and ovarian cancers associated with BRCA1/2 gene mutations more likely to recur.

Gloved hands putting individual tiny pipettes in a holder in a lab setting.

These mutations strongly predispose women to breast and ovarian cancers, and these cancers have a high risk of recurrence after initial treatment. In the new study, published in Nature Communications, the researchers compared a large set of tumors from patients with primary and recurrent BRCA1/2 mutation-associated breast and ovarian cancers, and found multiple features associated with recurrence, including features that would be expected to improve tumors’ ability to repair treatment-caused DNA damage.

“These results suggest key biological features of therapy-resistant recurrences, which point to new possibilities for treating BRCA1/2-mutation cancers,” says the study’s senior author Katherine Nathanson, the Pearl Basser Professor for BRCA-Related Research in the Perelman School of Medicine, deputy director of the Abramson Cancer Center, and director of Genetics at the Basser Center for BRCA.

The BRCA1 and BRCA2 proteins are key DNA-repair proteins. Their functional loss leaves some cells highly vulnerable to DNA damage, including damage that triggers cancer. Women with inactivating mutations in the BRCA1 or BRCA2 genes have very high lifetime risks of breast cancer, as well as high risks of ovarian cancer. Some women who learn that they have BRCA1/2 mutations opt for surgery to remove their breasts and ovaries to reduce their cancer risks, while others undergo close monitoring aimed at detecting cancers at the earliest stages.

Unfortunately, many women learn that they have a BRCA1/2 mutation only after breast or ovarian cancer has developed, often when the diseases are too advanced to be cured with surgery. These BRCA1/2-mutation-associated tumors often can be put into remission with chemo drugs and radiation, which take advantage of the tumors’ lower DNA-repair capacity. But these tumors have a high risk of recurrence within a few years after patients complete first-line therapy—and scientists know relatively little about the factors that drive recurrence.

Read more at Penn Medicine News.