SAN ANTONIO — Consider lowering the threshold for BRCA mutation testing in patients with early-onset breast cancer who have fewer than two first- or second-degree female relatives older than age 45, Dr. Jeffrey N. Weitzel advised at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
Patients with this sort of family situation, which he terms a “limited family structure,” were 3.5-fold more likely to carry a deleterious BRCA mutation than were early-onset breast cancer patients with an adequate family structure, in his observational study.
Selecting appropriate candidates for BRCA mutation testing can be a challenge.
Current guidelines agree that testing is not appropriate for women without breast cancer in the general population. But the guidelines are less clear regarding what to do about women who develop breast cancer at a young age in the absence of a family history of breast or ovarian cancer.
Consideration of family structure provides a quick, useful aid in this decision making, according to Dr. Weitzel, director of the department of clinical cancer genetics and the cancer screening and prevention program at City of Hope National Medical Center, Duarte, Calif.
He reported on 1,097 women who underwent BRCA mutation testing in the center's clinic for genetic cancer risk assessment. Of these women, 210 had breast cancer prior to age 50 and no family history of breast or ovarian cancer in first- or second-degree relatives. Half of these 210 women had a limited family structure.
A BRCA mutation was found in 17.3% of the women with early-onset breast cancer and a limited family structure, and in 5.7% of those with early-onset disease and an adequate family structure.
Family structure taken as a predictive factor for BRCA mutation had a sensitivity of 75% and a specificity of 54%.
Family structure's positive predictive value of 18% and negative predictive value of 91% were superior to the commonly used models for estimating the probability that a woman has a BRCA mutation—the Myriad Genetics, Couch, and BRCAPRO models.
None of those models proved sensitive to family structure as a risk factor, so consideration of family structure brings additional clinically relevant information to the table, Dr. Weitzel said.