Breast Cancer Combined with Primary Lung Cancer: A Study of Clinicopathologic Features and Prognostic Factors

We conducted a single-center retrospective study of patients with breast cancer (BC) who developed a second primary lung cancer (pLC) (BC-pLC; n = 54) versus BC only (n = 216) undergoing curative-intent surgery from 2012 to 2017, with follow-up through June 30, 2023. Clinicopathologic variables were compared; multivariable logistic regression estimated correlates of BC-pLC; survival was assessed with Kaplan-Meier estimates and Cox proportional-hazards models. Compared with BC, the BC-pLC cohort had higher frequencies of estrogen receptor-negative (ER-negative) and progesterone receptor-negative (PR-negative) tumors and more Ki-67-positive tumors; after multiplicity adjustment (Bonferroni), ER negativity and Ki-67 positivity remained significant, whereas human epidermal growth factor receptor 2 (HER2) did not. In multivariable analyses, larger tumor size (>2 cm) and Ki-67 positivity were independently associated with BC-pLC (odds ratio [OR] 3.02, 95% CI 1.29-7.38; OR 3.10, 95% CI 1.32-7.49). At the cohort level, differences in overall survival (OS) and invasive disease-free survival (iDFS) between BC-pLC and BC were not statistically significant after adjustment. Biomarker-stratified analyses showed worse OS for ER-negative tumors and nominally better iDFS for Ki-67-negative tumors. Tumor burden and proliferative activity can guide risk-stratified chest imaging surveillance and early pathology correlation to distinguish metastasis from new primaries during BC follow-up.