Increased risk of lung cancer after breast cancer radiation therapy in cigarette smokers

BACKGROUND: Ionizing radiation is a lung carcinogen in a variety of settings, including after breast cancer radiation therapy. The authors explored whether cigarette smoking and breast cancer radiation therapy have a multiplicative effect on the risk of subsequent lung cancer. METHODS: This case-control study investigated women registered with primary breast cancer in the Connecticut Tumor Registry who developed a second malignancy between 1986 and 1989. Those diagnosed with a subsequent primary lung cancer were compared with those diagnosed with a subsequent nonsmoking, nonradiation-related second malignancy, and age-adjusted odds ratios were calculated with logistic regression. RESULTS: No radiation effects were observed within 10 years of initial primary breast cancer. Among both smokers and nonsmokers diagnosed with second primary cancers more than 10 years after an initial primary breast cancer, radiation therapy was associated with a 3-fold increased risk of lung cancer. A multiplicative effect was observed, with women exposed to both cigarette smoking and breast cancer radiation therapy having a relative risk of 32.7 (95% confidence interval CI, 6.9-154). The radiation carcinogenic effect was observed only for the ipsilateral lung and not for the contralateral lung both in smokers and nonsmokers. CONCLUSIONS: Breast cancer radiation therapy, as delivered before 1980, increased the risk of lung cancer after ten years in nonsmokers, and a multiplicative effect was observed in smokers. For both smokers and nonsmokers, this effect was observed only for the ipsilateral lung and not the contralateral lung. Modern techniques, however, significantly decrease the radiation dose to the lungs, which may decrease the risk of lung cancer. Nonetheless, due to the available choices in early-stage breast cancer treatment, current practices may need to be revised for young breast cancer patients who smoke.