Abstract PL02-03: The DARC side of breast cancer disparities: Links to African ancestry and immunologic tumor responses

Abstract

Abstract The disparities in breast cancer mortality among ethnic and race groups in the United States, with highest morality in African Americans (AAs), has persisted for five decades. However, even with the typical delays in diagnosis, more advanced stage distribution at diagnosis, and inadequate multidisciplinary breast cancer treatment, these combined factors do not completely explain breast cancer survival outcomes, which persist after controlling for stage at diagnosis. Paradoxically, population breast cancer mortality rates were similar for both groups until the early-1980’s, at which point the mortality curves separated because of declining mortality rates in WAs contrasted against relatively stable mortality rates in AAs. The mortality gap that emerged very likely reflected the unmasking of differences in the biology of breast cancer between AA and WA women related to prevalence of biomarker expression and the development of targeted therapy for breast cancer cases that were treatable with these therapies, as indicated by target gene expression (i.e. Estrogen Receptor). Unfortunately, the advancement of targeted therapies has failed to address cancers that are more prevalent in non-white patient groups. In fact, the approximately two-fold increased risk of Triple Negative Breast Cancer (TNBC) in AA women has been confirmed by population-based incidence rates regionally as well as nationally, and across all age intervals. Compared to non-TNBC, triple negative disease has been confirmed to be an adverse prognostic feature in AA patients, driving some of the mortality disparities. From a global perspective, epidemiological studies of breast cancer incidence and prevalence across the African diaspora resonate a similar theme, that women of African descent have a worse clinical outcome worldwide. Our team has investigated African tumor phenotypes, identifying distribution patterns that are similar among West African women from Nigeria and Ghana. Like the US, these global poor outcomes are also coupled with higher incidence of TNBC among women with western, sub-Saharan African ancestry, across each continent. Interestingly, even within Africa, there are distinctive differences in TNBC frequency between women of West African descent compared to those of East African descent, where East Africans have lower incidence of TNBC. As, historical and genetic evidence indicate that most AA share ancestry with women in West Africa rather than East Africa. These observations suggest a geographic ancestry connection with tumor biology and imply biological differences in tumors may permeate throughout the world population, associated with ancestral lineage. Genomic expression analyses have been utilized in cancer disparities for more than two decades. In this presentation, Dr. Davis will highlight the historical progression of cancer genomics in cancer disparities and expound on recent findings from her research group, the International Center for the Study of Breast Cancer Subtypes. Overall, there are similar themes emerging across race-group analyses that implicate immunological pathways in disparities of tumor phenotypes and clinical outcomes. Specifically, recent reports from ICSBCS show that African-Specific alleles can play a significant role in cancer disease progression, particularly with regard to immune response in tumorigenesis. Citation Format: Melissa B. Davis. The DARC side of breast cancer disparities: Links to African ancestry and immunologic tumor responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr PL02-03.