Association between Breast Cancer and Second Primary Lung Cancer among the Female Population in Taiwan: A Nationwide Population-Based Cohort Study

SIMPLE SUMMARY: There is an increasing number of patients with breast cancer and second primary lung cancer clinically. The aim of our population-based cohort study was to investigate this correlation in Taiwanese women using the National Health Insurance Research Database from Taiwan National Health Insurance. We confirmed that patients with breast cancer had a significantly higher risk of developing second primary lung cancer compared with patients without breast cancer, particularly in younger groups and in those without any comorbidities. The special association is meant to raise awareness and provoke interest in routine lung cancer screening for female patients who were diagnosed with breast cancer at a relatively young age. ABSTRACT: Purpose: A special association between breast cancer and second primary lung cancer in Taiwanese women has been discovered not only in clinical practice, but also in a large population-based study. We hereby investigate the association between breast cancer and second primary lung cancer in Taiwanese women. Methods: This study was conducted from the National Health Insurance Research Database (NHIRD) from Taiwan National Health Insurance (NHI). Patients older than 18 years old and hospitalized with a first diagnosis of breast cancer during 2000 to 2012 were enrolled in the breast cancer group. Patients who were cancer free were frequency-matched with the breast cancer group by age (every five-year span) and index year. The ratio of breast cancer group to non-breast cancer group was 1:4. The event as the outcome in this study was lung cancer. The comorbidities viewed as important confounding factors included coronary artery disease, stroke, hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, tuberculosis, chronic kidney disease, and chronic liver disease and cirrhosis. We estimated the hazard ratios (HRs), adjusted hazard ratios (aHRs), and 95% confidence intervals (CIs) for risk of lung cancer in the breast cancer group and non-breast cancer group using Cox proportional hazard models. Sensitivity analysis was also done using propensity score matching. All of the statistical analyses were performed using SAS statistical software, version 9.4 (SAS Institute Inc., Cary, NC). Results: There were 94,451 breast cancer patients in the breast cancer group and 377,804 patients in the non-breast cancer group in this study. After being stratified by age, urbanization level, and comorbidities, the patients with breast cancer had a significantly higher risk of lung cancer compared with the patients without breast cancer, particularly for those who aged between 20 and 49 years (aHR = 2.10, 95% CI = 1.71–2.58), 50 and 64 years (aHR = 1.35, 95% CI = 1.15–1.58), and those without any comorbidities (aHR = 1.92, 95% CI = 1.64–2.23). Conclusion: Patients with breast cancer had a significantly higher risk of developing second primary lung cancer compared with patients without breast cancer, particularly in younger groups and in those without any comorbidities. The special association may be attributed to some potential risk factors such as genetic susceptibility and long-term exposure to PM2.5, and is supposed to increase public awareness. Further studies are necessary given the fact that inherited genotypes, different subtypes of breast cancer and lung cancer, and other unrecognized etiologies may play vital roles in both cancers’ development.