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Effect of Breast Cancer Radiotherapy and Cigarette Smoking on Risk of Second Primary Lung Cancer

Elizabeth L. Kaufman, Judith S. Jacobson, Dawn L. Hershman, Manisha Desai, Alfred I. Neugut

From the Departments of Epidemiology and Biostatistics, Mailman School of Public Health; Department of Medicine and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University; and the Division of Medical Oncology, New York Presbyterian Hospital, New York, NY

Corresponding author: Alfred I. Neugut, MD, PhD, Division of Medical Oncology, Columbia University Medical Center, 722 W 168th St, MSPH 725, New York, NY 10032; e-mail: ain1{at}columbia.edu

Purpose Prior studies have found that postmastectomy radiotherapy (PMRT) for breast cancer (BC) increases the risk of lung cancer (LC). We explored the joint effects of cigarette smoking and PMRT on LC risk.

Methods We conducted a population-based nested case-control study among women registered in the Connecticut Tumor Registry diagnosed with nonmetastatic BC between January 1, 1965 and December 31, 1989. Patient cases developed a LC 10 years after BC diagnosis. Controls were matched to patient cases on age, year of BC diagnosis, and length of survival. Medical records were reviewed for pathology, BC therapy, and smoking history. We used conditional logistic regression to estimate odds ratios for the independent and joint effects of smoking and PMRT on risk of overall, ipsilateral, and contralateral LC.

Results Among 113 second primary LC patient cases and 364 controls, compared with nonsmoking women who did not receive PMRT, nonsmoking women who received PMRT had no higher risk of LC; adjusted odds ratios were 5.9 (95% CI, 2.7 to 12.8) for ever-smokers who did not receive PMRT and 18.9 (95% CI, 7.9 to 45.4) for ever-smokers who received PMRT. Adjusted odds ratios for the joint effects of smoking and PMRT were 10.5 (95% CI, 2.9 to 37.8) for the contralateral lung and 37.6 (95% CI, 10.2 to 139.0) for the ipsilateral lung. Smoking and PMRT were associated with increased risk for all histologic types of LC.

Conclusion PMRT after a diagnosis of BC sharply increased the risk of second primary LC, especially in the ipsilateral lung, among ever-smokers. Clinicians should consider including smoking history in their discussions with patients about the risks and benefits of PMRT.

Supported by a supplement to National Cancer Institute (NCI) Grant No. P30 CA13696 and in part by a K07 award from NCI (Grant No. CA95597; to D.L.H.).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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