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Ionizing Radiation and Tobacco Use Increases the Risk of a Subsequent Lung Carcinoma in Women With Breast Cancer: Case-Only Design

From the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; Department of Hospital Physics, Radiumhemmet, and Department of Medicine, Clinical Epidemiology Unit, Karolinska University Hospital; Department of Medical Radiation Physics, Stockholm University, Stockholm, Sweden; and Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC.

Address reprint requests to Michaela Prochazka, RN, MPH, Department of Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77, Stockholm, Sweden; e-mail: Michaela.Prochazka{at}meb.ki.se

PURPOSE: To analyze the risk of lung cancer in women treated with radiotherapy for breast cancer. We accessed the lung dose in relation to different radiotherapy techniques, provided the excess relative risk (ERR) estimate for radiation-associated lung cancer, and evaluated the influence of tobacco use.

PATIENTS AND METHODS: The Swedish Cancer Registry was used to identify 182 women diagnosed with breast and subsequent lung cancers in Stockholm County during 1958 to 2000. Radiotherapy was administered to 116 patients. Radiation dose was estimated from the original treatment charts, and information on smoking history was searched for in case records and among relatives. The risk of lung cancer was assessed in a case-only approach, where each woman contributed a pair of lungs.

RESULTS: The average mean lung dose to the ipsilateral lung was 17.2 Gy (range, 7.1 to 32.0 Gy). A significantly increased relative risk (RR) of a subsequent ipsilateral lung cancer was observed at 10 years of follow-up (RR = 2.04; 95% CI, 1.24 to 3.36). Squamous cell carcinoma (RR = 4.00; 95% CI, 1.50 to 10.66) was the histopathologic subgroup most closely related to ionizing radiation. The effect of radiotherapy was restricted to smokers only (RR = 3.08; 95% CI, 1.61 to 5.91). The ERR/Gy for women with latency 10 years after exposure was 0.11 (95% CI, 0.02 to 0.44).

CONCLUSION: Radiotherapy for breast cancer significantly increases the risk of lung carcinoma more than 10 years after exposure in women who smoked at time of breast cancer.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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