Surgical resection for indeterminate pulmonary nodules in patients with prior breast cancer: diagnostic value and biomarker reassessment.

Background: Pulmonary nodules detected during postoperative surveillance in breast cancer survivors present a diagnostic challenge because imaging findings alone often cannot reliably distinguish pulmonary metastases from primary lung cancer. Surgical resection provides definitive pathological diagnosis while simultaneously enabling biomarker reassessment in metastatic lesions. This study evaluated the diagnostic value and clinical significance of pulmonary resection for indeterminate pulmonary nodules in patients with prior breast cancer. Methods: We retrospectively reviewed 33 pulmonary resections performed in 32 consecutive patients with a history of breast cancer who underwent pulmonary resection for indeterminate pulmonary nodules between 2016 and 2025. Clinicopathological findings, imaging characteristics, perioperative outcomes, and receptor discordance between primary breast tumors and pulmonary metastatic lesions were analyzed. Paired biomarker data were available for 18 patients with pulmonary metastases. Results: Final pathological diagnoses included metastatic breast cancer in 23 lesions (69.7%), primary lung cancer in 9 lesions (27.3%), and benign disease in 1 lesion (3.0%), indicating that more than one-quarter of lesions suspected preoperatively to represent pulmonary metastases were actually primary lung cancers. Most procedures were performed using video-assisted thoracoscopic surgery (87.9%). Among patients with paired biomarker data, substantial discordance in hormone receptor and human epidermal growth factor receptor 2 (HER2) expression was observed, including frequent conversion between HER2-0 and HER2-low categories. Biomarker reassessment resulted in modification of subsequent systemic treatment in three patients. Perioperative outcomes were favorable, with no operative mortality and low postoperative morbidity. Conclusions: Surgical resection for indeterminate pulmonary nodules in selected patients with prior breast cancer provides definitive pathological diagnosis, appropriate local treatment, and sufficient tissue for biomarker reassessment. Histological confirmation should be considered when imaging findings remain inconclusive because pulmonary nodules in breast cancer survivors are not necessarily metastatic disease. Biomarker reassessment may directly influence individualized systemic treatment strategies in the HER2-low era.