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Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 − tumors are characterized by increased homologous recombination deficiency signature, pervasive  TP53  mutations, and greater structural variation—indicating aggressive biology.  GATA3  mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with  PIK3CA  and  CDH1  mutations, which are underrepresented in Nigerians and Blacks.  PLK2 ,  KDM6A , and  B2M  are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.

Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features