Preventing Cancer in BRCA Mutation Carriers

Every woman with a mutated BRCA1 or BRCA2 gene should have their ovaries removed to lower their risk of ovarian cancer, said Susan Domchek, MD, during an educational session Wednesday at the San Antonio Breast Cancer Symposium.

Prophylactic oophorectomy, the surgical removal of the ovaries, is most effective when a carrier is premenopausal, she told attendees.

Calling the preventive surgery “mandatory” in BRCA1 and BRCA2 mutation carriers, Domchek, of the Abramson Cancer Center in Pennsylvania, said there’s no evidence that current ovarian cancer screening is effective. Plus, age matters.

Women who carry a genetic mutation in either the BRCA1 or BRCA2 gene are at a substantially higher risk for both breast and ovarian cancer than the general population. For carriers who want to lower their risk of breast cancer, prophylactic mastectomy can reduce this risk by more than 90 percent, said Domchek, stopping shy of giving it the “mandatory” stamp.

For women with breast or ovarian cancer who know they carry a BRCA1 or BRCA2 mutation, the risk of a second cancer adds another layer of medical decision-making. An ovarian cancer patient, for instance, may be concerned about her breast cancer risk. However, Domchek said that for the first few years after diagnosis, these patients' cancer risk is largely driven by possible recurrence of their original cancer.

“They have to remember that their dominant risk is the cancer they already have—not the cancer that they then might get,” she said. As a patient gets further out from treatment, Domchek said she starts screening with breast MRI. She puts any discussions about preventive mastectomy on hold for at least two years.

For women seeking a therapeutic rather than a surgical approach, a new class of drugs called PARP inhibitors might have a role in prevention. Researchers recently found that inhibiting PARP, an enzyme that fixes DNA damage in both healthy cells and cancer cells, can effectively treat breast and ovarian cancer in women with BRCA mutations. (Read more about PARP inhibitors in Fall 2010’s "A New Hope".) Investigators hope that since the thinking is that if these drugs can treat BRCA-related tumors, maybe they can prevent them as well.

A prevention study using a PARP inhibitor in women who carry a BRCA mutation is about to start at Dana-Farber Cancer Institute, said Domchek. Considering the newness of the PARP inhibitors, she urged caution until the data are in.