Abstract 1338: Breast cancer survival of <i>BRCA1/2</i> carriers compared to non-<i>BRCA1/2</i> carriers in a large breast cancer cohort.
Authors: Marjanka MK Schmidt, Alexandra J. van den Broek, Rob AEM Tollenaar, Flora E. van Leeuwen, Laura J. Van ‘t Veer
Journal: Cancer Research (2013)

Abstract The biological background and different pathological aspects of BRCA1-associated tumors support the hypothesis that patients carrying a BRCA1 and/or BRCA2 mutation might have a worse breast cancer prognosis compared to non-carriers. However, studies showed inconsistent results, possibly due to differences in study design, study size, study populations and methodological quality. We recently performed a systematic review taking into account the quality of all relevant studies published so far on BRCA1/2 mutation carriership and survival (n=63). Using a best-evidence synthesis, we found that there is only moderate evidence for a worse unadjusted recurrence-free survival for BRCA1 mutation carriers compared to non-carriers (pooled absolute survival difference of 10%) (to be submitted). The aim of the current study was to evaluate breast cancer outcome in a multicenter cohort of breast cancer patients with long-term follow-up, unselected for family history. We included invasive pathologically-confirmed breast cancers, diagnosed before &amp;lt;50 years of age, in the period 1970-2002, in ten Dutch centers, in patients with no previous malignancies. DNA for BRCA1/2 analyses was isolated from formalin-fixed, paraffin-embedded tissue blocks containing normal (non-tumor) tissue. A selection of most frequently occurring BRCA1/2 mutations was analyzed using Taqman PCR and fragment length analyses confirmed by direct sequencing, capturing ∼70% of all Dutch pathogenic mutations. Clinico-pathological data and follow-up, including recurrences and second tumors, were retrieved from tumor registries, medical records and the Dutch municipal registry. Part of the tumor characteristics (grade, ER, PR, HER2) was obtained by revision. Cox proportional hazard models were run using STATA; multivariate models were adjusted for grade, size, nodal status and age. Among 5518 breast cancer patients with a BRCA1/2 result we found 3.6% BRCA1 and 1.2% BRCA2 mutation carriers. The proportions of ER-positive breast cancers in non-BRCA, BRCA1 and BRCA2 mutation carriers were 86%, 29% and 81% respectively. Mean follow-up of the cohort was 11.3 years. Overall survival was worse for BRCA1 mutation carriers compared to non-carriers (HR-unadjusted 1.4 (95%CI: 1.1-1.7), p=0.003; HR-adjusted 1.2 (1-1.6), p=0.07); recurrence-free survival was also worse for BRCA1 mutation carriers (HR-adjusted 1.5 (1.1-1.9), p=0.004). We did not find evidence for a different survival of BRCA2 mutation carriers, except for a suggestion of a worse overall survival. These results are preliminary and further analyses including stratifications by tumor subtype and treatment will be presented at the AACR meeting. In one of the largest, unbiased, BRCA1/2 genotyped breast cancer cohort study, we found evidence for a significant worse overall and recurrence-free survival adjusted for clinico-pathological factors of BRCA1 mutation carriers. Citation Format: Marjanka MK Schmidt, Alexandra J. van den Broek, Rob AEM Tollenaar, Flora E. van Leeuwen, Laura J. Van ‘t Veer, on behalf of collaborators of 10 centers in the Netherlands. Breast cancer survival of BRCA1/2 carriers compared to non-BRCA1/2 carriers in a large breast cancer cohort. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1338. doi:10.1158/1538-7445.AM2013-1338