Genome wide association studies have identified over 250 loci associated with breast cancer risk. Most loci contain many candidate causal variants (CCV) with molecular pleiotropy implicating multiple target genes, not all of which may be causal. CRISPR screens for cancer hallmark phenotypes offer a high throughput method to identify causal genes. We tested 1718 candidate target genes for effects on cellular proliferation (in 2D and 3D), in vivo tumour formation, DNA damage repair, and response to T cell killing. The cytotoxic T lymphocyte (CTL) evasion screen identified 63 candidate risk genes (FDR<0.2) using knockout and inhibition screens, including CASP8, CFLAR, and IRF1. We validated the top 14 candidate genes using in vitro breast cancer and CTL co-culture assay. We then employed luciferase reporter assays to demonstrate allele-dependent effects on candidate target gene expression. We demonstrated that the risk-associated alleles at rs736801 and rs3769821 lie in regulatory elements which reduce expression of IRF1 (the immune modulator) and CASP8 (the initiator caspase of extrinsic apoptosis), respectively. These effects are consistent with the activities observed in the screens. In conclusion, CRISPR screens are an efficient method to follow up GWAS findings to identify potential drug targets.