Medications to reduce breast cancer risk: a network meta-analysis of randomized controlled trials

Given the rising incidence of breast cancer, especially in premenopausal women, there is an urgent need to identify additional risk-reducing medications to accelerate prevention, as only a few are currently approved. Out of 8,598 studies screened, 43 RCTs (n = 337,240 women) met inclusion criteria. Six medications reduced overall breast cancer risk compared to placebo: sulfonylurea (RR = 0.18, NNT = 44.1, SUCRA = 0.90), thiazolidinediones (RR = 0.25, NNT = 48.3, SUCRA = 0.80), third-generation selective estrogen receptor modulators (SERMs) (RR = 0.46, NNT = 67.3, SUCRA = 0.62), aromatase inhibitors (AIs) (RR = 0.50, NNT = 73.0, SUCRA = 0.55), raloxifene (RR = 0.63, 95% CI = 0.47-0.84, NNT = 96.9, SUCRA = 0.37), and tamoxifen (RR = 0.76, NNT = 149.7, SUCRA = 0.23). AIs (RR = 0.48), tamoxifen (RR = 0.63, and raloxifene (RR = 0.63), were effective for invasive breast cancer. Third-generation SERMs (RR = 0.46), AIs (RR = 0.51), raloxifene (RR = 0.61), and tamoxifen (RR = 0.760.6) were effective in studies with breast cancer as a primary outcome, while thiazolidinediones (RR = 0.25) were effective in studies with breast cancer as a secondary/other outcome. We, therefore, performed network meta-analysis (NMA) to identify and compare the efficacy of medications for primary breast cancer prevention. This NMA confirms the efficacy of tamoxifen, raloxifene, and AIs, and identifies thiazolidinediones and third-generation SERMs as promising agents for breast cancer prevention, though not currently included in guidelines. These findings extend prior evidence and highlight the need for trials in premenopausal and racially diverse populations to address existing gaps.