Abstract C009: Race- and TNBC-specific circulating biomarker profiles among breast cancer patients
Authors: Martini Rachel , Amankwah Millicent , Sahler Julie , Stonaker Brian , Sadullozoda Mumina , Radzio Peter , August Avery , Newman Lisa , Davis Melissa 
Published: January 2023

Abstract
Triple negative breast cancer (TNBC) is the most aggressive molecular subtype of BC, with no targeted therapeutics currently available and poor systemic treatment response among certain patient groups. Cytokines, chemokines and adipokines are cell signaling molecules that play significant roles in mediation of inflammation/immune response in tumorigenesis and cancer progression. Relative systemic levels of these molecules secreted from the BC tumor microenvironment may be developed as prognostic liquid biopsy biomarkers. At present, we have investigated race-specific and TNBC-specific differences in circulating biomarker profiles of AA (n = 65) and EA (n = 88) BC patients. The International Center for the Study of Breast Cancer Subtypes (ICSBCS) maintains a prospective cohort biorepository of African and US patients, including patients from Detroit, MI (Henry Ford Health System) and New York City, NY (NewYork Presbyterian Hospitals). Using a multiplexed bead-based ELISA platform (Luminex®) we quantified the relative plasma levels of 45 different biomarkers per manufacturer’s protocols. Normalization of plate/batch effect was completed using MDimnNormn, and statistical tests were completed with JMP Pro 16. There were no significant differences between groups across most clinicopathological variables; including, age (p = 0.86), tumor histology (p = 0.45), subtype (p = 0.4039) or stage (p = 0.20). However, BMI was significantly higher among AA patients compared to EA patients (AA mean 31.5, EA mean 28.7, p = 0.016), and multivariate analyses were adjusted for BMI. Histological subtypes and stage represented a cross section of the cohort, with the majority being invasive ductal (AA 70.8%, EA 71.6%), and early-stage (Stage I and II) disease (AA 83.1%, EA 80.7%). The predominant intrinsic subtype is LumA (AA 69.2%, EA 67%), with a relatively higher proportion of TNBC disease among AA (20%) compared to EA patients (10.2%) (p = 0.086). Our univariate/unadjusted SRR-association models identified four biomarkers: IFNg (p = 0.022), I-TAC/CXCL11 (p = 0.003), MDC/CCL22 (p = 0.041) and MIPa/CCL3 (p = 0.038), which were higher among AA compared to EA patients. After controlling for BMI as a covariate in our model, all markers retained significance, with IFNg, I-TAC/CXCL11 and MIPa/CCL3 being p &lt; 0.05, and MDC/CCL22 with slightly lower significance (p = 0.054). To determine TNBC-specific profiles we compared biomarkers between TNBC (n = 22) and non-TNBC (n = 131) patients. The unadjusted/univariate analysis yielded no associations. However, after adjusting for BMI and SRR, 10 circulating biomarkers were significantly higher among patients with TNBC: IL16, MIF, TNFa, MPIF1/CCL23, IL1b, Gro-a/CXCL1, SCYB16/CXCL16, ENA-78/CXCL5, Fractalkine/CX3CL1 and Leptin (p &lt; 0.05). Taken together, these findings highlight that there are distinct SRR- and TNBC- circulating biomarker profiles, that may elucidate functional distinctions across TNBC patients to provide biomarkers for novel prognostic or therapeutic opportunities for patients.
Citation Format: Rachel Martini, Millicent Amankwah, Julie Sahler, Brian Stonaker, Mumina Sadullozoda, Peter Radzio, Avery August, Lisa Newman, Melissa Davis. Race- and TNBC-specific circulating biomarker profiles among breast cancer patients [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C009.