Several threads of evidence suggest a possible interplay between the HRD and APOBEC signature contributions, particularly in HR +/HER2 − breast cancers: (1) we identified racial/ethnic differences in mutation prevalence for TP53, CDH1, and PIK3CA; (2) we found associations between these mutations and mutation signatures (Fig. 3a); and (3) consistent with differential mutation status, HRD activity was increased in Nigerians, whereas APOBEC C > T displayed reduced activity in Nigerians and Blacks compared with Whites (Supplementary Fig. 7a). This evidence concerns the gene ERBB2 and breast cancer.