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Summary: In order to accurately detect and prevent racial disparities, self-reported race (SRR) and ethnicity remain valuable tools; however, inaccurate capture of patient identity and broad aggregation of minoritized race groups present challenges for data interpretation. Also, although SRR is a proxy for shared social/cultural experience, it is not an accurate representation of shared endogenous factors. Biological investigations into cancer disparities, particularly those involving genetic features, should be framed in the context of genetic background or ancestry, as these are heritable aspects of population health. In reality, both genetics and environment work in concert to influence cancer risk and clinical outcomes. The best opportunity to define actionable means for reducing health disparities is in rigorous and comprehensive generation of rich data sets that characterize environmental, biological, and genetic components of disparate disease burden. To translate this pivotal disparities research into clinical tools and improved policies, we describe a diversity, equity, inclusion, and accessibility (DEIA) framework, which will increase participation from diverse backgrounds, reexamine previous research with a rigorous evaluation of appropriate SRR groupings, and engage community leaders to ensure that future research addresses the needs of communities at increased risk. On this path forward, we may finally end cancer disparities.

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 < 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 < 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.

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Background: Breast cancer (BC) is a leading cause of cancer death in Ghana and around the world. Ghanaian women are diagnosed at younger ages with the more aggressive Triple Negative BC (TNBC) subtype where West African ancestry is associated with advanced BC diagnosis and higher mortality rates compared to age-matched women of European ancestry. Genomic comparisons of BC tumors from women of African and European ancestry show differences in frequencies of single nucleotide polymorphisms (SNP) and copy number variations. These differences may contribute to disparities in disease and treatment outcomes observed in women of African ancestry. Chemotherapy plays a major role in treatment of recurrent and metastatic BC. Long-term BC survival remains poor especially in Africa due to multidrug resistance (MDR). MDR has been associated with binding cassette (ABC) protein transporters. ABCB1, ABCC1 and ABCG2 are ABC transporter genes that code for proteins involved in drug efflux. We hypothesize that SNPs in ABC transporter genes may alter their physiological protective role and increase risk of MDR, treatment failure and death among BC patients. Preliminary dataWe explored gene expression profiles of ABCB1, ABCC1 and ABCG2 in an African ancestry-enriched subset of women with TNBC (ICSBCS cohort: Ghanaian n = 6, African American (AA) n = 9, Ethiopian n = 11). Preliminary data showed significantly higher expression of ABCC1 among Ghanaian and AA patients compared to Ethiopians, and a significant positive correlation with African ancestry. ABCB1 and ABCG2 showed lower expression in all three groups (ns).To study the relationship between ABC transporter gene SNPs and MDR, we have collected data over a 3-year period (2019-2021) from the Oncology Department of the Komfo Anokye Teaching Hospital in Ghana. The overall prevalence of BC recurrence was 3.4% (CI = 2.5 - 4.7%), and prevalence of metastatic BC was 47.6% (CI = 44.6 - 50.6%). Methodology: SNPs in ABC transporter genes will be obtained from 150 consented female BC patients who have undergone chemotherapy. We will compare genotype frequencies among patients with disease recurrence and/or metastasis (n = 100) to those with no disease recurrence or metastasis (n = 50). Single-plex genotyping of the ABC gene SNPs will be completed using a real-time PCR allelic discrimination assay. Conclusion: ABCC1 has been established to be associated with African ancestry. Determining the association of ABC gene SNPs and MDR among Ghanaian BC patients will provide further information on allelic variants and their effects on BC treatment outcomes. Citation Format: Gloria Agyekum Boaitey, Rachel Martini, Melissa B. Davis, Lisa Newman, Brian Stonaker, Linda Ahenkorah Fondjo, Christian Obirikorang, Ernest Osei Bonsu, Ernest Adjei, Ishmael Kyei, Mavis Bobie Ansah, Mahteme Bekele, Timothy Chu, Nicolas Robine. Evaluation of multidrug resistant genes among breast cancer patients in Ghana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2247.