Risk of breast, ovarian cancer may differ by type of BRCA mutation: study

Women who have inherited mutations in the BRCA1 or BRCA2 genes have an increased risk of breast and ovarian cancers, but the impact varies depending on the type and location of the mutations, researchers said Tuesday.

The results, published in the U.S. journal JAMA, may lead to more effective cancer risk assessment, care and prevention strategies for health care providers and BRCA1 or BRCA2 carriers.

"We've made a lot of progress toward understanding how to reduce the cancer risks associated with inherited mutations in BRCA1 or BRCA2 mutations, but until now, little has been known about how cancer risks differ by the specific mutation a woman has inherited," first author Timothy Rebbeck, professor of the University of Pennsylvania said in a statement.

"The results of this study are a first step in understanding how to personalize risk assessment around a woman's specific mutation, which can help guide carriers and providers in the cancer prevention decision making process," said Rebbeck, also associate director for Population Science at Penn Medicine's Abramson Cancer Center.

Rebbeck and colleagues analyzed more than 31,000 women from 33 countries who had mutations in the BRCA1 or BRCA2 genes.

Of the over 19,000 women with a BRCA1 mutation, 46 percent were diagnosed with breast cancer, 12 percent with ovarian cancer, 5 percent with breast and ovarian cancer, and 37 percent with no cancer.

Of the nearly 12,000 women with a BRCA2 mutation, 52 percent were diagnosed with breast cancer, 6 percent with ovarian cancer, 2 percent with breast and ovarian cancer, and 40 percent with no cancer.

Within the BRCA1 and BRCA2 genes, the researchers identified certain mutations that significantly increased or decreased a person's risk of breast or ovarian cancer.

Previously, a woman with a BRCA1 mutation would have been thought to have a 59 percent risk of breast cancer and a 34 percent risk for ovarian cancer, up until age 70.

However, the new research suggested that women who carry a specific subset of BRCA mutations most commonly present in the Ashkenazi Jewish population have a 69 percent risk of breast cancer and a 26 percent risk of ovarian cancer, for example.

The important question that remains is whether these differences will change the decisions a woman makes about preventive surgery or other behaviors, the researchers said.

"Additional research is needed to determine the absolute risks associated with different mutations, and how those differences might influence decision making and standards of care, such as preventive surgery, for carriers of BRCA1 and BRCA2 mutations," said senior author Katherine Nathanson, associate professor of Medicine and director of Genetics in the Basser Research Center for BRCA at Penn's Abramson Cancer Center.

BRCA1 and BRCA2 were thrown into the spotlight two years ago after film star Angelina Jolie, who carried a BRCA1 mutation, revealed her decision to get a preventive, bilateral mastectomy. Last month, Jolie announced she had undergone a second preventative surgery to have her ovaries and fallopian tubes removed. Endite