Abstract 866: Identification of novel early detection candidate protein biomarkers for ER+/PR+ invasive ductal breast carcinoma using pre-clinical plasma from the Women's Health Initiative Observational Study

Abstract

Abstract Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for approximately 45% of all invasive breast cancers (BC) diagnosed in the United States each year. While mammography screening and adjuvant hormonal therapy have played key roles in reducing breast cancer mortality, an important challenge remains the development of clinically useful blood-based biomarkers for early detection. The objective of this study was to identify and initially validate novel candidate markers for ER+/PR+ ductal BC, using pre-clinical plasma samples collected up to 12.5 months before diagnosis from 121 cases, 121 matched controls, and 201 non-matched controls from the Women's Health Initiative Observational Study. These specimens were equally divided into training and testing sets and interrogated by a customized antibody array, which included over 3,000 antibodies targeting more than 2,000 proteins. In the training set, statistically significant differences in matched case versus control signals were observed for 374 (11.4 %) antibodies at P<0.05, with 42 of these 374 candidates confirmed in the testing set (P<0.05). Four markers remained significant in the pooled matched pairs sample set after Bonferroni correction for multiple comparisons (P<0.05/3286=1.52x10-5). Areas under the curve for the full list of candidates ranged from 0.55 to 0.66, when assessed in an expanded sample including non-matched controls. With specificity set at 95%, sensitivity ranged from 4 to 19%, with six candidates having a sensitivity of ≥15% at 95% specificity and ≥20% at 90% specificity. The majority of these putative markers did not overlap with those identified in a parallel analysis of triple-negative BC from the same cohort population, suggesting the potential for BC sub-type specificity at the level of the pre-clinical plasma proteome. Additional studies are needed to validate these findings in larger sample sets and further explore their biologic implications in relation to ER+/PR+ BC etiology. Citation Format: Matthew F. Buas, Yuzheng Zhang, Junghyun Rho, Margaret Pepe, Paul Lampe, Christopher Li. Identification of novel early detection candidate protein biomarkers for ER+/PR+ invasive ductal breast carcinoma using pre-clinical plasma from the Women's Health Initiative Observational Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 866. doi:10.1158/1538-7445.AM2014-866