The genomic landscape of breast cancer in African American women

Background: According to several estimates, African American women are 40% more likely to die from breast cancer than white women in the United States. Proposed explanations for this disparity include differential socioeconomic factors and access to care, however some studies have raised the possibility that variation in tumor biology is a contributing factor. Methods: We prospectively sequenced primary and metastatic breast cancer tumors and their matched normal DNA using the MSK-IMPACT assay. We performed gene enrichment analyses to identify the oncogenic mutations and copy number alterations that were more frequent in patients who self-identified as African American or black (AA/B) compared with patients who self-identified as non-Hispanic white (NHW). Detailed clinicopathologic variables were collected for the full cohort. Mann-Whitney U test, Fisher’s exact test, and multivariate binomial regression models were used for statistical analyses. Results: Genomic profiling was performed on 339 tumors from 301 AA/B patients (44.6% metastatic), and 2,607 tumors from 2,248 NHW patients (48.5% metastatic). Age of AA/B and NHW patients at diagnosis was similar (51.5 vs. 52.8 years, p = 0.065). However, AA/B patients were more likely to be pre- or peri-menopausal at diagnosis (51.6 vs. 44%, p = 0.013), have triple-negative disease (26.5 vs. 13%, p 10, 0.9% vs. 0.5%; p = 0.44). Conclusions: In this large clinico-genomic analysis, as previously reported, AA/B patients were more likely to have the clinical hallmarks of aggressive disease, as defined by triple-negative subtype, higher stage, and premenopausal status at diagnosis. Our analysis demonstrated trends towards enrichment for some of the genomic alterations previously identified to be associated with poor outcome in the AA/B population, however, after controlling for the aforementioned clinical factors, breast cancer in AA/B did not differ significantly from breast cancer in NHW in terms of their driver genomic alterations, MSI or tumor mutation burden. Further studies are required to fully characterize the genomics of breast cancer in AA/B women, which may play a role in larger efforts to equalize the disparities observed in this population. Citation Format: Cristian Serna-Tamayo, Joshua Z Drago, Carlos Dos Anjos, Joshua Herbert, Fresia Pareja, Shanu Modi, Komal Jhaveri, Chau Dang, David B Solit, Larry Norton, Mauricio Scaltriti, Jorge S Reis-Filho, Sarat Chandarlapaty, Mark E. Robson, Pedram Razavi. The genomic landscape of breast cancer in African American women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-01.