Background: Women with inherited germline BRCA1/2 mutations have a 55-85% cumulative risk of breast cancer (BC) by age 70. Thus, knowledge of expected outcomes following various treatments is needed to advise these patients should they be diagnosed with BC. It is unclear whether breast conservation (BCT) offers similar rates of tumor control as mastectomy (M) in BRCA1/2 carriers and it is doubtful whether a randomized trial comparing these options could be performed. Thus, this analysis compares the outcomes between similarly staged women with BRCA1/2 mutations treated with BCT vs. M.Methods: Women with deleterious BRCA1/2 mutations diagnosed with operable BC and who consented to longitudinal studies were identified at 10 institutions in the US, Australia, Spain and Israel. Patient, clinical and treatment characteristics were compared between those receiving BCT and those receiving M +/- RT. Time-to-event endpoints included first failure of treatment, diagnosis of contralateral breast cancer (CBC), and overall and BC-specific survival. Cox regression models were constructed to detect significant associations between patient and clinical characteristics and time-to-event endpoints.Results: Clinical characteristics and outcomes for 302 BCT and 353 M patients were compared. With a median F/U of 8.2 years for BCT patients and 8.9 years following M, 15-year local failure as first failure was significantly higher with BCT vs. M (23.5% vs. 5.5%, p<0.0001). Multivariate analysis indicted choice of local therapy as the only factor significantly predicting local recurrence, with a 4.5-fold risk of local failure with BCT compared to M (p<0.0001). Local failure analyses by cohort revealed the presence of a BRCA2 mutation (HR 2.8; p=0.024) and no use of adjuvant chemotherapy (HR 5.4; p=0.0001) as significant predictors within the BCT group; presence of invasive lobular cancer (HR 9.9; p=0.004) was the only significant predictor within the M cohort. No significant differences were seen in distant failure, BC-specific or overall survival by local therapy. 15-year estimates of CBC were 52.1% with BCT; 41.4% with M; and 37.9% with M+RT (p=0.44). Analyses of BCT vs. M +/- RT and surgery +/- RT did not reveal significant differences in CBC by cohort.Conclusions: The higher risk of local failure in BRCA1/2-associated BC treated with BCT compared to M did not translate into an increased risk of distant failure or mortality. RT did not result in a detectable increase in CBC at 15 years above baseline elevated rates. These results at both the involved and contralateral breasts should be discussed when patients with BRCA1/2-associated BC are considering local treatment options. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 959.

No abstract

No abstract

No abstract