Abstract 713: Proteomic early detection biomarkers for ER+ breast cancer to improve mammography screening
Authors: Garrison Carly B. , Marsh Tracey , Buas Matthew , Zhang Yuzheng , Pepe Margaret , Lampe Paul D. , Li Christopher I. 
Published: July 2017

Abstract
There are clear clinical and public health needs to improve the early detection of breast cancer in order to save lives. Breast cancer is the leading cause of cancer death in women worldwide and is the second leading cause of cancer mortality in women in the United States. Although mammography is widely used to screen for breast cancer, it suffers both from false negative and false positive readings resulting in later diagnoses or unnecessary follow-up (e.g., biopsies), respectively. Improvement of breast cancer early detection may be possible through the measurement of minimally invasive, easy to perform blood based biomarkers.
Our studies were performed on pre-clinical plasma samples collected up to 12.5 months before breast cancer diagnosis from cases and matched controls obtained from the Women’s Health Initiative (WHI) Observational Study (a prospective cohort of 93,676 post-menopausal women). We utilized high-density antibody microarray methods for both discovery and preliminarily validation on distinct sample sets for early detection biomarkers of estrogen receptor positive (ER+) breast cancer (around 70% of all breast cancers are classified as ER+). Antibody microarray features (i.e., spots) identified as having ≥30% sensitivity at 80% specificity were considered to have met the cutoff criteria and identified as potential markers. A total of 129 features, corresponding to 101 proteins, were identified as potential markers in one WHI dataset (90 cases vs. 90 controls). Of the 129 features (101 proteins), 47 (34 proteins) validated by our cutoffs and demonstrated over or under-expression in cases compared to controls consistent with the first dataset in the second set of WHI samples (121 cases vs. 121 controls).
Given this level of reproducibility, we believe these biomarkers could be used to improve early detection of ER+ breast cancer for these clinical scenarios: 1. Informing timing of a subsequent mammogram in women with a negative screening mammogram; 2. Informing continuation of mammographic screening among women 75-79 years; 3. Prioritizing women who should be screened with mammography in areas with limited resources.
We are currently performing further validation of the protein markers in Early Detection Research Network (EDRN) specimen reference set from patients at the time of diagnosis. We plan to test our markers on a pre-diagnostic cohort from the Cardiovascular Health Study using a different, more clinically applicable platform. We used the same high-density antibody microarray platform to measure autoantibody-autoantigen complexes and sialyl Lewis-A and –X modifications in one of the WHI sample sets and are now testing these markers in the EDRN set for validation. Given the strength of our biomarker candidates, the high quality sets of biospecimens we used, the study designs employed, and the clearly delineated clinical applications proposed, we believe these markers could have near-term clinical impact.
Citation Format: Carly B. Garrison, Tracey Marsh, Matthew Buas, Yuzheng Zhang, Margaret Pepe, Paul D. Lampe, Christopher I. Li. Proteomic early detection biomarkers for ER+ breast cancer to improve mammography screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 713. doi:10.1158/1538-7445.AM2017-713