Genetically proxied inhibition of HMG-CoA reductase (OR: 0.84; 95% CI 0.74–0.95; P = 0.005) and NPC1L1 (OR: 0.72; 95% CI 0.58–0.90; P = 0.005) equivalent to a 1-mmol/L (38.7 mg/dL) reduction in LDL-C was associated with reduced breast cancer risk. Here, HMGCR is linked to breast cancer.