BACKGROUND: Women of African ancestry (WAA) are disproportionately affected by triple-negative breast cancer (TNBC), which remains one of the most clinically challenging breast cancer (BCa) subtypes. This study investigated the prevalence of TNBC and epidemiological trends for BCa in Barbados, a Caribbean island with a high percentage of African ancestry. METHODS: Pathology reports for all BCa cases between 2007 and 2016 were collected from the sole hospital in Barbados and reviewed. The clinicopathological data collected included age, tumor grade, lymph node status, and hormone receptor status as determined by immunohistochemistry. BCa data for non-Hispanic white (NHW) and non-Hispanic black (NHB) American populations were accessed from the Surveillance, Epidemiology, and End Results database. RESULTS: There were 1997 BCa cases in Barbados between 2007 and 2016 for an estimated incidence rate of 135.1 per 100,000 women in Barbados (standardized to the US population, where the standardized incidence rates for NHBs and NHWs were 141.4 and 152.6 per 100,000, respectively). Age-specific incidence rates in Barbados for this period were consistently higher in younger age groups (15-59 years) in comparison with NHWs and NHBs. Between 2010 and 2016 in Barbados, a TNBC prevalence of 25% was observed, whereas TNBC prevalences of 21% and 10% were observed in NHBs and NHWs, respectively. CONCLUSIONS: The BCa incidence was higher in younger Barbadian women than NHWs and NHBs, and the TNBC prevalence was ~2.5 times higher than the prevalence in NHWs. This hints at a possible genetic predisposition and other socioeconomic factors that could explain the high TNBC prevalence and aggressive clinical course in WAA globally. Cancer 2020;126:2217-2224.

Purpose Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African ancestry (WAA) and is often associated with poor survival. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. Methods This multisite cross-sectional study used 31 formalin-fixed paraffin-embedded (FFPE) samples from Barbadian and Nigerian TNBC participants. High-resolution whole exome sequencing (WES) was performed on the Barbadian and Nigerian TNBC samples to identify their mutational profiles and comparisons were made to African American, European American and Asian American sequencing data obtained from The Cancer Genome Atlas (TCGA). Whole exome sequencing was conducted on tumors with an average of 382 × coverage and 4335 × coverage for pooled germline non-tumor samples. Results Variants detected at high frequency in our WAA cohorts were found in the following genes NBPF12, PLIN4, TP53 and BRCA1. In the TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-African American; 67% in TCGA-European American; 63% in TCGA-Asian). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-African American cohort. For copy number variants, high frequency alterations were observed in PIK3CA, TP53, FGFR2 and HIF1AN genes. Conclusion This study provides novel insights into the underlying genomic alterations in WAA TNBC samples and shines light on the importance of inclusion of under-represented populations in cancer genomics and biomarker studies.

Women of African ancestry (WAA) are disproportionately affected by the aggressive triple negative breast cancer (TNBC) subtype that is often associated with high recurrence rates and metastasis. Although there is a high prevalence of TNBC across West Africa and in women of the African diaspora, there has been no comprehensive genomics study to investigate the mutational profile of ancestrally related women across the Caribbean and West Africa. To shed more light on this phenomenon, whole exome sequencing (WES) was performed on 31 formalin-fixed paraffin-embedded TNBC tissues from ancestrally related Barbadian and Nigerian women. We compared these genomics profiles with data from The Cancer Genome Atlas (TCGA) for African American (TCGA-AA), European American (TCGA-EA) women with TNBC. With an average coverage of 382x for tumour samples (n= 31) and 4335x for pooled germline (n=22) non-tumor samples, the most mutated genes in our cohorts include NBPF12, PLIN4, TP53 and BRCA1. For TCGA TNBC cases, these genes had a lower mutation rate, except for TP53 (32% in our cohort; 63% in TCGA-AA; 67% in TCGA-EA). For all altered genes, there were no differences in frequency of mutations between WAA TNBC groups including the TCGA-AA cohort. Additionally, we observed a high frequency of copy number variant alterations in PIK3CA, TP53, FGFR2 and HIF1AN genes. This study provides in-depth insights into the underlying genomic alterations in WAA-TNBC samples and shines light on the importance of inclusion of non-European populations in cancer genomics and biomarker studies. Citation Format: Shawn M. Hercules, Xiyu Liu, Blessing I. Bassey-Archibong, Desiree H.A. Skeete, Suzanne Smith Connell, Adetola Daramola, Adekunbiola A.F. Banjo, Godwin Ebughe, Thomas Agan, Ima-Obong Ekanem, Joe E. Udosen, Christopher Obiorah, Aaron C. Ojule, Michael A. Misauno, Ayuba M. Dauda, Ejike C. Egbujo, Jevon C. Hercules, Amna Ansari, Ian Brain, Christine MacColl, Yili Xu, Yuxin Jin, Sharon Chang, John D. Carpten, André Bédard, Gregory R. Pond, Kim R.M. Blenman, Zarko Manojlovic, Juliet M. Daniel. Analysis of the genomic landscapes of Barbadian and Nigerian women with triple negative breast cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-142.