Abstract P055: Risk factors for second primary lung cancer among breast cancer survivors
Authors: Choi Eunji , Lee Justin , Wu Julie T. , Wakelee Heather A. , Schapira Lidia , Kurian Allison W. , Han Summer S. 
Published: January 2023

Abstract
Introduction: Breast cancer is the most common cancer in women in the U.S. As survival in breast cancer has improved, one of the key clinical problems in breast cancer survivors is the increased risk of second cancers. Over half (55%) of breast cancer survivors die from second cancers, of which lung cancer (i.e., second primary lung cancer [SPLC]) is the most frequent type. While smoking and radiotherapy have been identified as the risk factors for SPLC among breast cancer survivors, other potential factors (e.g., comorbidity, and medication) have been underexamined. In addition, women in general have shown higher susceptibility to smoking-induced lung cancer than men, suggesting the potential involvement of hormonal factors; however, the effect of hormone replacement therapy (HRT) on lung cancer risk has been controversial and has never been examined among breast cancer survivors. We aimed to examine the factors associated with SPLC risk among breast cancer survivors, focusing on the effect of HRT and its interaction with smoking. We also explored the potential of tailored risk-based management of SPLC for breast cancer survivors. Methods: We identified 5,552 patients diagnosed with breast cancer in 1993-2014 from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. SPLC was defined as a newly diagnosed lung cancer after 6 months from the time of breast cancer diagnosis. We applied multivariable cause-specific Cox regression to identify new factors associated with SPLC risk, adjusting for multiple testing using the Bonferroni method (P&lt;0.01). We developed a prediction model to predict a 5-year risk of SPLC among breast cancer survivors that included both ever- and never-smokers and evaluated the predictive accuracy vs. a well-established lung cancer risk model, PLCOm2012, that was developed for a cancer-free population who ever smoked. Results: Of 5,552 patients, 89 (1.6%) developed SPLC over 102,545 person-years. Several factors measured at baseline in PLCO were significantly associated with SPLC risk among breast cancer survivors, including liver comorbidity (Hazard Ratio [HR] 3.28; P&lt;.001), prior history of other cancer (HR 2.02; P=0.01), and regular use of ibuprofen (HR 0.52; P=0.01). In addition, ever-use of HRT was associated with a 51% reduction in SPLC risk (HR 0.49; P=0.001). The effect of active smoking on SPLC risk vs non-active smoking (HR 7.09; P&lt;.001) was validated in PLCO. Notably, the effect of active smoking was intensified among ever-HRT users (HR=10.5; P&lt;.001) vs. never-HRT users (HR 4.1; P&lt;.001), thus showing a significant interaction (Pinteraction=0.003). The prediction model for SPLC risk was validated through bootstrap and demonstrated higher discrimination (AUC 0.83) vs. the PLCOm2012 model (AUC 0.79). Conclusions: In a large prospective cohort of breast cancer survivors, smoking and HRT use showed a significant interaction on SPLC risk. The prediction model for SPLC could identify high-risk survivors for SPLC for tailored surveillance to improve the management of breast cancer survivors.
Citation Format: Eunji Choi, Justin Lee, Julie T. Wu, Heather A. Wakelee, Lidia Schapira, Allison W. Kurian, Summer S. Han. Risk factors for second primary lung cancer among breast cancer survivors. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P055.