Risk of developing a second primary cancer in male breast cancer survivors: a systematic review and meta-analysis

Background With increasing survival after cancer diagnoses, second primary cancers (SPCs) are becoming more prevalent. We investigated the incidence and site of non-breast SPC risks following male breast cancer (BC). Methods PubMed, Embase and Web of Science were systematically searched for studies reporting standardised incidence ratios (SIRs) for SPCs published by March 2022. Meta-analyses used the generic inverse-variance method, assuming a random-effects model. We evaluated SIRs for overall SPCs, site-specific risks, by age at BC onset, time since BC onset and geographic region. We assessed study quality using routine techniques. Results Eight population-based retrospective cohort studies were identified. SIRs ranged from 1.05 to 2.17. The summary SIR estimate was 1.27 (95% CI: 1.03-1.56, I-2: 86%), and there were increased colorectal (SIR: 1.29, 95% CI: 1.03-1.61), pancreatic (SIR: 1.64, 95% CI: 1.05-2.55) and thyroid (SIR: 5.58, 95% CI: 1.04-30.05) SPC risks. When an outlying study was excluded, the summary SIR for men diagnosed with BC before age 50 was 1.50 (95% CI: 1.21-1.85), significantly higher than men diagnosed at older ages (SIR: 1.14, 95% CI: 0.98-1.33). Conclusions Male BC survivors are at elevated risks of developing second primary colorectal, pancreatic and thyroid cancers. The estimates may assist their clinical management and guide decisions on genetic testing.