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Solving a Puzzle in BRCA1-caused Breast Cancers

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Research Roundup

Susan F. Smith Center for Women’s Cancers

Women who carry a mutant BRCA1 gene are at high risk of developing aggressive breast cancers. Most of the tumors are “ER-negative,” meaning they aren’t driven by the estrogen hormone and thus don’t respond to estrogen-blocking agents.

But about 20 percent of breast cancers in BRCA1 carriers are ER-positive. Research by Susan F. Smith Center for Women’s Cancers scientist Daniel Silver, MD, PhD, is exploring this puzzling minority.

“We were wondering about these ER-positive tumors,” says Dr. Silver, “Where do they come from? Are they caused by the mutant BRCA1 gene, or are they sporadic, meaning they just happen to develop in a BRCA1 carrier but aren’t related to the mutation?

The latter explanation seemed unlikely after a recent study found that the ER-positive tumors in BRCA1 carriers differed from those that developed in women without the BRCA1 mutation. Among other things, the tumors associated with BRCA1 mutations were more aggressive.

In the current study, Silver’s team found that ER-positive and ER-negative tumors in mutation carriers shared similarities. Both tumor types arose from BRCA1-deficient cells. This is important clinically, says Silver, because “it is likely that the ER-positive cancers will benefit from the some of the new therapies used to treat ER-negative tumors in these patients.” These include platinum-based chemotherapeutic agents and new targeted drugs known as PARP inhibitors.


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