Effects of smoking and radiotherapy on lung carcinoma in breast carcinoma survivors

BACKGROUND The combined effects of thoracic radiotherapy (XRT) and cigarette smoking are not known with certainty, but they have important implications for lung carcinogenesis after cancer therapy in some patients. The authors analyzed smoking, radiation, and both exposures on lung carcinoma development in women who were treated previously for breast carcinoma. METHODS Case patients (n = 280) were female residents of the United States, ages 30–89 years, with breast carcinoma prior to primary lung carcinoma diagnosed between 1960 and 1997. Control patients (n = 300) were selected randomly from 37,000 patients with breast carcinoma who were treated at The University of Texas M. D. Anderson Cancer Center and frequency matched with women in the case group based on age at diagnosis (5‐year strata), ethnicity, year of breast carcinoma diagnosis (5‐year strata), and survival from breast carcinoma diagnosis to lung carcinoma diagnosis. Using stratified analysis and unconditional logistic regression, the authors evaluated the main and combined effects of smoking and XRT on lung carcinoma risk. RESULTS At the time of breast carcinoma diagnosis, 84% of case patients had ever smoked cigarettes, compared with 37% of control patients, whereas 45% of case patients and control patients received XRT for breast carcinoma. Smoking increased the odds of lung carcinoma in women without XRT (odds ratio [OR], 6.0; 95% confidence interval [95% CI], 3.6–10.1), but XRT did not increase lung carcinoma risk in nonsmoking women (OR, 0.5; 95% CI, 0.3–1.1). Overall, the OR for both XRT and smoking, compared with no XRT or smoking, was 9.0 (95% CI, 5.1–15.9). Logistic regression modeling yielded an adjusted OR of 5.6 for the smoking main effect (95% CI, 2.9–10.5), 0.6 for the XRT main effect (95% CI, 0.3–1.4), and 8.6 (P = 0.08) for the combined effect. CONCLUSIONS Smoking was a significant independent risk factor for lung carcinoma after breast carcinoma, but XRT alone was not. Smoking and XRT combined enhanced the effect of either alone, with marked increased risks of lung carcinoma after XRT for breast carcinoma. Cancer 2003;98:1457–64. © 2003 American Cancer Society. DOI 10.1002/cncr.11669 The combined effects of thoracic radiotherapy and cigarette smoking are not known with certainty, but they have important implications for lung carcinogenesis after cancer therapy in some patients. In a hospital based case–control study, the authors observed a marked increase in the risk of lung ca