We showed that, based on individual’s genotype, CTSO contributes differentially to tamoxifen response in ERα-positive (ER+) breast cancer cells by regulating ZNF423 and BRCA1levels and that PARP inhibitors can effectively restore tamoxifen sensitivity in subjects with unfavorable genotypes of CTSO and ZNF423 associated with tamoxifen resistance. Here, ZNF423 is linked to breast cancer.