The observation in this study that BRCA1 or BRCA2 mutations can substitute for SV40-T/t antigens for transformation by hTERT+PIK3CAH1047R suggests that aberration in signaling molecules that co-operate with BRCA1 or BRCA2 in DNA repair pathways could be the second mutation along with a PIK3CA mutation needed to initiate breast cancer. This evidence concerns the gene BRCA1 and breast carcinoma.