Abstract P4-02-05: A blinded multicenter phase II study of a panel of plasma biomarkers for the detection of triple negative breast cancer
Authors: Anderson Karen S , Pepe Margaret , Marks Jeffrey , Engstrom Paul , Patriotis Christos , Zangar Richard , Skates Steven , Lampe Paul , LaBaer Joshua , Li Christopher I 
Published: May 2015

Abstract
Background: Triple negative breast cancers (TNBC) comprise 15-20% of all breast cancers and frequently present as interval cancers with high proliferative rates and increased risk of mortality. There is a clinical need for biomarkers for the early detection of TNBC to complement radiologic imaging. No plasma biomarkers for TNBC currently exist. The purpose of this study is to evaluate a panel of novel plasma biomarkers for TNBC for the discrimination of TNBC and benign breast disease as a crucial step in identifying a panel of plasma biomarkers for early detection.
Methods: In a multicenter collaboration between the NCI EDRN and the CPTAC consortium, we conducted a prospective blinded phase II biomarker study that evaluated 76 candidate TNBC plasma biomarkers. Plasma samples collected at the time of diagnosis from 65 TNBC cases and 195 matched controls with benign breast disease without atypia were identified from multiple clinical sites. The samples were distributed as blinded aliquots to the biomarker laboratories for protein and autoantibody detection. Candidate protein (n=54) and autoantibody (n=22) biomarkers were selected and ranked prior to evaluation. All results were centrally analyzed. The sensitivity at 95% specificity was calculated for each biomarker. Effects of age, race, and specimen source on biomarkers were evaluated. Logistic regression was used to assess complementarity of biomarkers. The top three biomarkers underwent verification with an independent set of 60 TNBC cases and 180 matched controls from women undergoing mammography.
Results: Statistically significant differences in case versus control signals were observed for 3 biomarkers with sensitivities of 17-23% at 95% specificity (p &lt;0.008, unadjusted) and areas under the curve of 0.55-0.57. These three biomarkers were confirmed in the independent set of 60 cases and 180 controls with sensitivities 12-23% at 95% specificity and cross-validated combined sensitivity of 27%. In the subset of women ages 50-79 (cases n=38, controls n=119), five biomarkers were identified with sensitivities of 15.7-16.2% at 95% specificity (p&lt;0.10).
Conclusion: We have developed a pipeline strategy for the validation of plasma biomarkers for detection of breast cancer. At least three biomarkers for TNBC were confirmed in this study. Further evaluation of these biomarkers for early detection is ongoing.
Citation Format: Karen S Anderson, Margaret Pepe, Jeffrey Marks, Paul Engstrom, Christos Patriotis, Richard Zangar, Steven Skates, Paul Lampe, Joshua LaBaer, Christopher I Li. A blinded multicenter phase II study of a panel of plasma biomarkers for the detection of triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-02-05.