Breast Cancer
Ovarian Cancer

Hereditary Breast and Ovarian Cancers: Moving Toward More Precise Prevention

By NIH Director Francis Collins, M.D., Ph.D.

Inherited mutations in the BRCA1 gene and closely related BRCA2 gene account for about 5 to 10 percent of all breast cancers and 15 percent of ovarian cancers [1]. For any given individual, the likelihood that one of these mutations is responsible goes up significantly in the presence of  a strong family history of developing such cancers at a relatively early age. Recently, actress Angelina Jolie revealed that she’d had her ovaries removed to reduce her risk of ovarian cancer—news that follows her courageous disclosure a couple of years ago that she’d undergone a prophylactic double mastectomy after learning she’d inherited a mutated version of BRCA1.

As life-saving as genetic testing and preventive surgery may be for certain individuals, it remains unclear exactly which women with BRCA1/2 mutations stand to benefit from these drastic measures. For example, it’s been estimated that about 65 percent of women born with a BRCA1 mutation will develop invasive breast cancer over the course of their lives—which means approximately 35 percent will not. How can women in this situation be provided with more precise, individualized guidance on cancer prevention? An international team, led by NIH-funded researchers at the University of Pennsylvania, recently took an important first step towards answering that complex question.

In a study published in the journal JAMA, the researchers analyzed genetic data and health information from more than 31,000 women with mutations in BRCA1/2. They found that among such women, the answer to whether a particular individual will develop breast cancer, ovarian cancer, both types of cancer, or neither cancer appears to vary considerably depending upon two factors: the precise type of mutation inherited and the locations of these mutations in the DNA sequences of the genes [2].

We’ve known about the roles of BRCA1 and BRCA2 in inherited breast and ovarian cancer for some time. The tumor suppressor genes, which code for proteins involved in DNA repair, were first isolated 20 years ago. However, over the years, we’ve also learned that each of these genes can contain different types of inherited mutations that vary among the individuals/families being studied. Until we understand with far greater precision how each of these many mutations (or even groups of mutations) affects individual cancer susceptibility, the best that health-care professionals can do is to offer BRCA1/2 carriers prevention guidance based on general risk calculations.