To analyze the effects of metformin in reducing radiation-induced cardiac toxicity (RICT) risk during adjuvant radiotherapy (RT) after surgery for early-stage breast cancer women. We compare the consecutive occurrence of major heart events (heart failure and coronary artery disease) in women with early-stage breast cancer receiving adjuvant breast RT with metformin and in those receiving RT without metformin. A retrospective national cohort study was conducted using the Taiwan Cancer Registry of 2004-2014. This study included 6,993 women with early-stage breast cancer who received adjuvant breast RT. Metformin users were defined as patients prescribed metformin for >28 days during adjuvant breast RT. An inverse probability of treatment weighting (IPTW) Cox hazards model was used to estimate metformin effects on the occurrence of major heart events. Among women with breast cancer status post-surgery under adjuvant breast RT, 2,062 were prescribed metformin and 4,931 were not prescribed metformin. Cox proportional hazard regression analysis, with adjustment using IPTW, indicated that metformin use during adjuvant breast RT significantly reduces the risk of major heart events (adjusted hazard ratio [aHR], 0.789; 95% confidence interval [CI], 0.645-0.965; P = 0.021). In another negative control exposure, thiazolidinedione use during adjuvant breast RT did not statistically reduce consecutive RICT risk (aHR, 1.106; 95% CI, 0.768-1.594; P = 0.589). Our results suggest that metformin use during adjuvant breast RT was associated with reduced RICT risk in women with early-stage breast cancer.
Keywords: Radiation-induced cardiac toxicity; adjuvant breast radiotherapy; breast cancer; metformin.