Risk of primary lung cancer after breast cancer radiotherapy: a systematic review and meta-analysis.

Background: Epidemiological studies have shown that the risk of secondary malignancies may increase by radiotherapy. Lung cancer is the most important long-term complication of breast cancer radiotherapy.

Methods: Major electronic databases including Scopus, Web of Science, and MEDLINE were searched. All cohort studies that investigated the association between radiotherapy for breast cancer and risk of primary lung, bronchus, and trachea cancers conducted until March 2021 were included. The study participants were evaluated regardless of their age and ethnicity. The Newcastle-Ottawa Scale was used to assess the quality of the studies. The designated effects were risk ratio (RR). The random-effects model was used to estimate the average effects.

Results: Fifteen studies including 1,640,247 women with primary breast cancer were identified of which 937,151 had not received radiotherapy and 703,096 subjects had received radiotherapy. In general, there was no significant association between breast cancer radiotherapy and lung cancer based on 10 studies (RR = 0.95, 95% CI 0.87-1.02, P = 0.15), There was no association between breast cancer radiotherapy and lung, bronchus, and trachea cancers either based on 5 studies (RR = 0.98, 95% CI 0.93-1.02, P = 0.32).

Conclusion: Radiotherapy for breast cancer is not associated with an excess risk of lung cancer. Due to the limited number of studies, lack of data regarding smoking status, and substantial variation in exposure of the lungs in breast cancer radiotherapy worldwide, further investigations based on randomized controlled trials are suggested to address the potential risk of lung cancer after breast cancer radiotherapy.