Risk of Developing Second Primary Lung Cancer After Receiving Radiation for Breast Cancer
Lye-Yeng Wong*, Ntemena Kapula, Douglas Liou, Natalie S. Lui, Leah M. Backhus, Mark F. Berry, Joseph B. Shrager, Irmina A. Elliott
Cardiothoracic Surgery, Stanford, Mountain View, CA
Breast cancer is a highly curable disease with long patient survivorship. Radiotherapy (RT) is an integral aspect of multimodality treatment, especially in the current era that emphasizes breast conservation. In prior studies, RT has been demonstrated to be associated with the development of a second primary lung cancer, with risk ratios cited up to 2.0 for patients who live for 10 years beyond their breast cancer diagnosis. Our study aims to determine the incidence of subsequent primary lung cancer after RT exposure for breast cancer over a timespan of three decades to quantify this risk over time as modern oncologic treatment continues to advance.
The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1988 to 2014 for all patients diagnosed with non-metastatic breast cancer, and patients who subsequently developed primary lung cancer were identified. Multivariable regression modeling was performed to identify independent factors associated with the development of lung cancer. Sub-analysis was performed examining the hazard ratios (HR) of developing a second primary lung cancer stratified by follow up intervals of 5-9, 10-15, and 15+ years post-breast cancer diagnosis.
Of the 691,514 patients who met inclusion criteria, 353,035 (51%) patients received RT as part of their breast cancer treatment. 6,148 (1.7%) patients in the RT group versus 5,547 (1.6%) patients in the non-RT group developed a second primary lung cancer. In the overall multivariable model, RT for breast cancer was not associated with an increase in overall lung cancer (HR 0.99 [95% CI 0.95-1.04], p-value=0.69), nor lung cancer on the ipsilateral side as the prior breast cancer (HR 1.04, [95% CI 0.98-1.11], p-value=0.19). However, in sub-analysis stratified by length of follow-up interval, in the cohort of patients with 5-9 year follow-up, the overall HR of developing subsequent lung cancer was 1.12 ( p=0.004), in patients with 10-15 year follow-up, the HR was 1.18 (p=0.003), and in the 15+ year follow-up interval, the HR was 1.21 (p=0.008) (Figure).
Exposure to RT for breast cancer treatment does increase the risk of developing a subsequent primary lung cancer as the follow-up interval increases, but this increased risk is much lower than previously published. Although longer survivorship is associated with increasing risk, the clinical impact is seemingly small. Modern RT techniques over the last few decades may have contributed to the improvement in risk profile and this updated study is important for the counseling and surveillance of breast cancer patients.
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