Risk of Second Primary Lung Cancer in Women After Radiotherapy for Breast Cancer

Background: Several epidemiological studies have reported increased risks of second lung cancers after breast cancer irradiation. In this study we assessed the effects of the delivered radiation dose to the lung and the risk of second primary lung cancer.

Methods: We conducted a nested case-control study of second lung cancer in a population based cohort of 23,627 early breast cancer patients treated with post-operative radiotherapy from 1982 to 2007. The cohort included 151 cases diagnosed with second primary lung cancer and 443 controls. Individual dose-reconstructions were performed and the delivered dose to the center of the second lung tumor and the comparable location for the controls were estimated, based on the patient specific radiotherapy charts.

Results: The median age at breast cancer diagnosis was 54 years (range 34-74). The median time from breast cancer treatment to second lung cancer diagnosis was 12 years (range 1-26 years). 91% of the cases were categorized as ever smokers vs. 40% among the controls. For patients diagnosed with a second primary lung cancer five or more years after breast cancer treatment the rate of lung cancer increased linearly with 8.5% per Gray (95% confidence interval=3.1-23.3%; p<0.001). This rate was enhanced for ever smokers with an excess rate of 17.3% per Gray (95% CI=4.5-54%; p<0.005).

Conclusions: Second lung cancer after radiotherapy for early breast cancer is associated with the delivered dose to the lung. Although the absolute risk is relative low, the growing number of long-time survivors after breast cancer treatment highlights the need for advances in normal tissue sparing radiation techniques.