Abstract

Abstract Background: BCL-2 is an antiapoptotic protein that regulates apoptosis and has been associated with poor prognosis for many cancer sites. Despite a function that encourages tumorigenesis, increased BCL-2 expression has been associated with improved clinical outcomes in ER+ breast cancers, with mixed results observed for ER/PR- cancers. BCL-2 has been hypothesized to be an indicator of intact and fully functioning hormone receptor pathways and has also been hypothesized to facilitate cell death after treatment through mitochondrial priming. BCL-2 expression correlates strongly with hormone receptor expression; therefore, its association with better prognosis may be due to the strong effect ER/PR status has on survival, or due to its own biologic mechanism. To date, no studies have been conducted on racial differences in BCL-2 expression. We characterized racial/ethnic differences in BCL-2 expression and the association of BCL-2 expression with breast cancer specific survival among participants in the Breast Cancer Care in Chicago Study (BCCC). Methods: The BCCC was a cross-sectional study of 989 recently diagnosed non-Latina (nL) White, nL Black and Latina breast cancer patients diagnosed with a first primary breast cancer aged 30-79 in Chicago from 2005-2008. Tumor tissue was available for BCL-2 immunohistochemical staining for 264 patients. BCL-2 staining scores of 0 were classified as negative and all positive scores (1D, 1H, 2D, 2H, and 3) were classified as positive. Cox proportional hazards models were conducted to estimate the association of BCL-2 expression with breast cancer-specific death. Results: Roughly three-fourths of tumors (77%) stained positive for BCL. The prevalence of positive BCL staining varied by race/ethnicity (p=0.007), being highest for nL Whites (87%) and lowest for nL Blacks (68%); variability in BCL staining appeared to be limited to ER/PR-negative tumors (N=53), for which prevalence of positive BCL staining appeared to be much higher for nL whites than for minority patients (44% vs. 16%, p=0.054). BCL-2 expression was associated with a strong protective effect on BC survival in age and race-adjusted models (HR=0.40, 95% CI: 0.19, 0.84) and BCL-2 expression remained strongly positively associated with protection from breast cancer death with additional adjustment for ER/PR status (HR=0.33, 95% CI: 0.12, 0.89). Within subgroups defined by ER/PR status, BCL2 expression was qualitatively associated with better survival for both ER/PR positive and ER/PR negative subtypes, although sample size was insufficient to conduct a formal stratified analysis. Conclusions: BCL-2 appears to be an independent predictor of improved prognosis for breast cancer even after controlling for ER/PR status. The apparently higher prevalence of BCL2 expression for nL White vs. nL Black patients may provide etiologic clues regarding disparities in BC survival. Citation Format: Jibril M. Alim, Kent Hoskins, Abeer M. Mahmoud, Virgilia Macias, Andre Kadjascy-Balla, Garth H. Rauscher. Racial disparity in the prevalence of BCL-2 expression and associations with breast cancer survival in the Breast Cancer Care in Chicago study [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C098.

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