PURPOSE: Guidelines for BRCA1/2 testing recommend first testing a relative with cancer (proband) and, if a mutation is found, offering testing to other family members. We compared the current practice of proband testing with directly testing an unaffected woman relative without first testing the proband.

METHODS: We used a Markov model to evaluate two testing strategies. The first strategy (Proband Testing) tests the identified relative with cancer and then if she is found to carry a BRCA1/2 mutation tests an unaffected relative. The second strategy (Unaffected-Woman Testing) tests the unaffected relative who is seeking testing without first testing the proband. We evaluated women from two populations: a “high-risk” general population (women with first degree relative with either ovarian cancer or breast cancer before age 35); and a “high-risk” Ashkenazi Jewish population (women with a first degree relative with either ovarian cancer or breast cancer before age 40). We evaluated four scenarios in which women have all combinations of high utilities (0.97) or low utilities (0.83) for prophylactic oophorectomy and mastectomy.

RESULTS: In the high-risk general population (prevalence BRCA1/2 = 8% in probands), Unaffected-Woman Testing resulted in slightly more quality-adjusted life years (QALYs) than did Proband Testing for women whose preference for prophylactic oophorectomy and/or mastectomy is high (range of 3.5 to 4.4 quality-adjusted days). The incremental cost-effectiveness ratio (ICER) of Unaffected-Woman testing compared to proband testing is < $50,000/QALY in each scenario. In unaffected women whose utilities for both surgeries were low, no BRCA1/2 testing is the preferred strategy. For high-risk Ashkenazi Jewish women, (prevalence BRCA1/2 = 20% in probands), Unaffected-Woman Testing was associated with more QALYs than Proband Testing (2.8 quality-adjusted days) for women whose preference for either prophylactic mastectomy or prophylactic oophorectomy was high (ICER approximately $20,000/QALY). For women who have a high utility for prophylactic mastectomy and for prophylactic oophorectomy, Proband Testing was recommended before testing the unaffected woman. For women whose utilities for both surgeries were low, it was cost-effective ($66,623/QALY) to first test the proband before testing the unaffected woman.

CONCLUSIONS: Although current recommendations suggest testing probands first, our analysis found that testing an unaffected relative first is a reasonable option depending on a woman's utilities for prophylactic surgery. These findings have implication for testing guidelines.