When the BRCA test is negative-Prevention strategies in women who have no detectable mutation (BRCA-) compared to women harboring positive BRCA mutations (BRCA+).

1534 Background: Much attention has been focused on screening and risk reduction, including prophylactic mastectomy (PM) or oophorectomy (PO) in BRCA+ mutation carriers (Rebbeck 1999, Eisen 2005, Kauff 2007). In families with a known BRCA mutation (BRCA+) or a history of hereditary breast cancer (BC) or ovarian cancer (OC), relatives in whom a mutation is not identified are considered 'high risk' and prevention strategies, including the need for PM or PO are undefined. We undertook a prospective evaluation of relatives from families wherein a BRCA mutation was present, with the intent to understand how BRCA- members view and manage their risks of BC or OC over time.,Participants were 1st and 2nd degree unaffected relatives of 27 BRCA+ patients known to have BC or OC (20 BRCA1 and 7 BRCA2), referred to the high risk clinic for screening and prevention advice. Prior to and following genetic testing, participants were evaluated for individual risk factors for BC, self-perceived risk of BC, anxiety, prevention preferences and intentions. Genetic testing identified 62 BRCA+ (med. age 44) and 53 BRCA- (med. age 39) relatives, median Gail scores were 3.10 and 2.59 respectively.,Prior to genetic testing, 90% of all patients, regardless of BRCA status reported 'extreme' anxiety and a 'very high' perceived lifetime risk of BC. Two-thirds expressed interest in PM and/or PO. After genetic testing, 50% and 90% in the BRCA+ cohort, and 20% and 32% in the BRCA- cohort underwent PM and PO respectively. Less than 10% chose chemoprevention (CP) in both groups. At 6 months post PM or PO 80% and 65% of BRCA+ and BRCA- cohorts expressed decisional satisfaction. Significant factors determining PM in the BRCA- cohort were: age (>40), 1st degree relative with BC, family history of BRCA1 mutation, 'high' anxiety persisting >1 year.,BRCA- relatives of BRCA+ families believe that they are highly susceptible to BC, experiencing high anxiety post-test disclosure and have an unexpectedly high rate of PM and PO. CP is unexpectedly low in both cohorts. Improved strategies for assessment and management of risk in these patients are required. No significant financial relationships to disclose.