Risk and Influencing Factors for Subsequent Primary Lung Cancer After Treatment of Breast Cancer: A Systematic Review and Two Meta-Analyses Based on Four Million Cases

IntroductionTo compare the risk of developing lung cancer between patients with breast cancer and the general population and explore the risk factors for the development of primary lung cancer after treatment for breast cancer.MethodsThe PubMed, EMBASE, and Web of Science databases were searched from the establishment date to October 11, 2020. Two separate meta-analyses were performed: one focused on studies reporting the risk of subsequent lung cancer after breast cancer and one focused on studies exploring the risk factors for subsequent lung cancer in patients with breast cancer. The standardized incidence ratios with 95% confidence intervals were combined to compare the risk of developing lung cancer between patients with breast cancer and the general population. The relative risks (RRs) or ORs with 95% confidence intervals were combined to assess the association of clinicopathological parameters with the risk of developing lung cancer after breast cancer. All statistical analyses were conducted by STATA 12.0.ResultsA total of 15 studies involving 1,161,979 patients were eventually included in the first meta-analysis, and the pooled results indicated that female patients with breast cancer revealed a significantly higher risk of developing subsequent lung cancer (standardized incidence ratio = 1.25, p < 0.001). In addition, a total of 22 articles involving 3,090,620 patients were included in the second meta-analysis. The pooled results indicated that smoking (OR = 9.73, p < 0.001) and radiotherapy (RR = 1.40, p < 0.001) were risk factors for developing subsequent lung cancer in patients with breast cancer, and chemotherapy (RR = 0.69, p = 0.002), positive estrogen receptor status (RR = 0.93, p = 0.014) and positive progesterone receptor status (RR = 0.86, p < 0.001) were protective factors. Meanwhile, subgroup analysis based on the relative position of the breast and lung cancers (ipsilateral versus contralateral) was conducted, which indicated that radiotherapy only increased the risk of ipsilateral lung cancer in patients with breast cancer (RR = 1.27, p = 0.001).ConclusionsPatients with breast cancer are more likely to develop lung cancer than the general population, and the risk of developing primary lung cancer after breast cancer is affected by smoking, radiotherapy, chemotherapy, estrogen receptor status and progesterone receptor status.