Abstract 1030: Pathology, BRCA status, and ancestry among Hispanics with breast cancer
Authors: Clague Jessica , Martir-Negron Arelis E. , Ogaz Raquel , Herzog Josef , Port Danielle , Sand Sharon , Weitzel Jeffrey N. 
Published: August 2012

Abstract
Purpose: Classical epidemiologic approaches to breast cancer (BC) causation may benefit from the identification of particularly high-risk subsets such as BRCA carriers, given that Hispanics appear to have one of the highest rates (25%) of BRCA mutations among women with BC. A pilot study suggested a lower rate of progesterone receptor (PR) BC among BRCA-positive Hispanics vs non-Hispanic whites (Lagos, BreastCancerResTreat, 2011). Methods: We investigated the pathological characteristics of BC in Hispanics, along with ancestral admixture, stratified by BRCA status in a large cohort of Hispanics with a personal or family history of breast and/or ovarian cancer. All subjects were enrolled in an IRB-approved registry and underwent genetic cancer risk assessment (GCRA) and BRCA testing within a consortium of 14 high-risk clinics across the US. Multigenerational pedigrees and data on grandparental geographic origins, as well as epidemiologic factors, were obtained at the initial GCRA visit. Clinical information was abstracted from pathology reports. Genotyping of 59 ancestry informative markers (AIMs) and STRUCTURE analysis was performed to determine differences in ancestry. Results: Of the 746 Hispanic individuals enrolled, 610 were diagnosed with invasive breast cancer. Among the BC cases, 152 (25%) had deleterious BRCA mutations (98 in BRCA1, 54 in BRCA2), 30 (5%) had one or more unclassified variants, and 428 (70%) had a negative result. The overall mean age of diagnosis was 40.5 years (±8.8); no difference was observed by BRCA status. Overall, 39.9% of cases were estrogen receptor (ER)-negative, 50.2% were PR-negative and 74.2% HER2-negative (7.4% were negative for ER, PR and HER2). BRCA1 carriers were more likely to have ER-negative and PR-negative tumors than either BRCA2 carriers or non-carriers (P&lt;0.001) and no difference in hormone receptor status was observed between BRCA2 carriers and non-carriers (P&gt;0.05). Mean percentage of European ancestry was highest among BRCA2 carriers (54.5%) compared to non-carriers (51.6%) and BRCA1 carriers (46.3%; P&lt;0.05). Higher European and lower AmerIndian ancestry was observed among cases with HER2-positive tumors versus negative tumors (P&lt;0.05). Conclusions: To date, this is the largest study of high-risk Hispanic families in the US with complete BRCA testing, multigenerational pedigrees, and detailed clinical and ancestral data. Interestingly, the rate of PR negativity was much higher than what has been reported among non-Hispanic whites in the literature. This supports our pilot study observations. Since PR has been found to be an independent predictor of endocrine therapy response, further study of lower levels of PR in the Hispanic population is warranted. Data on non-Hispanic white women is currently being collected for direct comparison. Additional research is needed to investigate the potential unique BC immunophenotypes and genetic profiles by ancestral background.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1030. doi:1538-7445.AM2012-1030