An in-depth look at the issues associated with the care of women in families with hereditary breast and ovarian cancer syndrome who have not yet developed cancer themselves reveals a need to improve how clinicians can help these women sort through their options.

In the article, published in the New England Journal of Medicine (doi:10.1056/NEJMra1503523), Lynn Hartmann, MD, Mayo Clinic oncologist and lead author, and Noralane Lindor, MD, a pathologist and genetics expert, argue for greater support for women grappling with complex and emotionally charged decisions, and more research to devise improved treatment approaches for hereditary breast and ovarian cancer syndrome.

Mutations in BRCA1 and BRCA2 genes are the most common genetic defects in women with a family history of hereditary breast and ovarian cancer syndrome. BRCA1 and BRCA2 mutations are often lumped together as BRCA1/2, as if the risks and susceptibilities to cancer type are the same for both gene mutations. However, the diseases spawned by the two mutations can be very different.

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Average cumulative risks are 67% for breast cancer and 45% for ovarian cancer by age 80 years for women who carry the BRCA1 mutation. Average cumulative risks for women who carry the BRCA2 mutation are 66% for breast cancer and 12% for ovarian cancer.

Most cases of breast cancer in BRCA1 mutation carriers are high-grade, triple-negative disease. In contrast, breast cancers in BRCA2 mutation carriers are mostly ER-positive disease. These differences include significantly different prognostic and treatment ramifications, as risk-reducing medications are available for ER-positive breast cancer but not for ER-negative disease.

Ovarian cancer is also different in women with one of the two gene mutations. The disease typically develops earlier and with greater frequency in BRCA1 mutation carriers than in BRCA2 mutation carriers.

Current guidelines recommend salpingo-oophorectomy for women ages 35 to 40 years who have no further plans for childbearing. The authors, however, believe women who carry the BRCA2 mutation can hold off undergoing the procedure until they are 45 years old, as they have a 1% risk of developing ovarian cancer by age 50 years.

“Many of the studies we discuss were published recently, so we are taking advantage of the increased knowledge of the types of cancers that these women develop and the ages at which they occur to suggest how we can change our thinking around their management,” says Hartmann.