FORCE has a strong commitment to promoting research to benefit our community. We advocate for more research funding, educate people about available studies, and report findings back to our community.
by Tracy M. Diaz
Women from high-risk families live with awareness of their heightened risk. Even for women who test negative in a family with a known BRCA mutation, it is sometimes difficult to let go of the fear of cancer. In 2007, a British research study written by Smith et. al. suggested that female family members of BRCA1/BRCA2 mutation carriers who tested negative for the gene mutation still carried a 5-fold increased risk of developing breast cancer. Many well-regarded genetics experts disputed this finding. FORCE published an article on this study in a previous FORCE newsletter. A recent study by Dr. Allison Kurian, of Stanford University, pulished in the Journal of Clinical Oncology, refutes the Smith study and shows that noncarriers in BRCA families do not have an increased risk of breast cancer.
Researchers looked at 3047 families enrolled in the Breast Cancer Family Registry (BCFR) sites in Australia, Canada, and Northern California that have tested for BRCA mutations. Of those tested, 160 were found to have BRCA1 mutations and 132 had BRCA2 mutations. In order to calculate breast cancer risk for noncarriers, the no mutation carrying first degree relatives (FDRs) of BRCA positive breast cancer patients were compared to the FDRs of breast cancer patients without BRCA mutations. In this comparison the relative risk for breast cancer was not'significantly increased in non-mutation carriers from BRCA families compared with those from families who did not have BRCA. The comparison of 292 BRCA mutation carrying families to 2755 families without BRCA mutations in this study is the largest analysis of breast cancer risk for non-mutation-carriers from BRCA families.
In an accompanying editorial to Dr. Kurian's article, Dr. Mark E. Robson, Director of Clinical Genetics at Memorial Sloan-Kettering discusses the limitations of prior studies as well as how the Kurian study is different. Dr. Kurian's approach is considered more representative of the cancer risk in this population than Smith's study. The conclusion drawn from this and prior studies is that women who are mutation negative are not at a high enough increased risk to justify specialized surveillance or preventive strategies. While Dr. Robson cautions that this study, along with previous studies, does not exclude the possibility that mutation negative women are at a slightly higher cancer risk than women in the general population, it does show that the magnitude of the increased risk is not sufficient for noncarriers to be advised like their mutation carrying family members.
Kurian AW, Gong GD, John EM, Wittemore AS, et al. Breast cancer risk for noncarriers of family-specific BRCA1 and BRCA2 mutations: Findings from the Breast Cancer Family Registry. Journal of Clinical Oncology, vol. 29(33), November, 2011.
Robson, M. Do Women Remain at Risk Even If They Do Not Inherit a Familial BRCA1/2 Mutation? Journal of Clinical Oncology; vol. 29(33), November, 2011.
Smith, A, Moran, A, Boyd, MC, et. al. Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening. J Med Genet. 2007; vol. 44(1), January, 2007.