Deciding who should be screened for the BRCA1 and BRCA2 gene variants that increase the risk of breast and ovarian cancer became a bit more complicated recently after Dr. Mary-Claire King, the scientist who discovered the BRCA1 gene, made the bold recommendation that all adult women should be screened for these variants beginning at age 30. In contemporary clinical practice, healthcare providers generally recommend BRCA1 and BRCA2 screening based on personal and family history and ancestry. Dr. King, however, asserts that screening the general population is a better way to identify women who are BRCA1 and BRCA2 carriers so that healthcare providers can better monitor them and deliver early intervention to reduce their cancer risk.
Dr. King based her recommendation on the results of a study that she and her colleagues conducted in a population of Ashkenazi Jewish men and women in Israel. The investigators screened more than 8000 healthy Ashkenazi Jewish men for 3 specific variants in BRCA1 and BRCA2 known to account for the majority of inherited cancer risk in this population. Screening men rather than women may seem like an odd approach, but keep in mind that BRCA1 and BRCA2 variants are equally common in both women and men and are inherited equally from mothers and fathers. Screening men for the variants enabled the researchers to identify female carriers based on their relationship to a male relative rather than on their personal or family history of cancer.
The results showed that among female relatives who were carriers, cumulative risk of developing either breast or ovarian cancer by age 60 was 60% for BRCA1 carriers and 33% for BRCA2 carriers. Half of the families found to harbor BRCA1 or BRCA2 variants had no history of breast or ovarian cancer that would have led their healthcare providers to recommend screening. Without population-based screening, the women in these families would not have known they were carriers until they developed cancer.
And that’s the concern among geneticists and breast cancer advocates. Just because a woman carries one of the BRCA1 or BRCA2 variants doesn’t mean she will ultimately develop cancer. As these results show, there was a 40% risk of not developing breast or ovarian cancer by age 60 in BRCA1 carriers. A woman who learns she carries one of these genes may make the decision to undergo radical surgery she might not even need. Another concern: can we extrapolate the results of this study conducted in a relatively genetically homogenous population to the entire population of the United States? We know that the number and frequency of BRCA1 and BRCA2 variants vary among populations. The results of 1 study in the Ashkenazi Jewish population in Israel simply don’t provide enough evidence to support screening all adult women in the United States.
Hayes agrees that women, when armed with knowledge, can make wise, informed decisions that improve their health. Certainly, population-based screening programs have their place in clinical practice. But at this point in time, we just don’t have enough evidence to support screening all women for BRCA1 and BRCA2. Until more evidence accumulates, we would advise women to do what they can to modify their cancer risk—exercise, maintain a healthy weight, eat a healthy diet, and follow screening guidelines for the low-risk population. If women are concerned they may be at risk to be a BRCA1 or BRCA2 carrier, we urge them to discuss their concerns with their healthcare providers to determine the best approach for each individual.