Second primary driver-negative lung adenocarcinoma following breast cancer treatment: a case report

We present the case of a 60-year-old non-smoking woman previously treated for luminal B human epidermal growth factor receptor 2 (HER2)-positive invasive breast carcinoma with surgery, AC60 chemotherapy, trastuzumab, breast radiotherapy, and hormone therapy at the Mohammed VI Oncology Center in Casablanca, Morocco. Four years after completing treatment, she presented with respiratory symptoms and was diagnosed with a well-differentiated, lepidic-type mucinous primary lung adenocarcinoma, staged IIIA (pT2bN1M0). Molecular analysis showed the absence of epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) and ROS1 rearrangements, rearranged during transfection (RET) fusions, and MET exon 14 skipping, with intermediate programmed death-ligand 1 (PD-L1) expression, assessed by tumor proportion score (TPS) of 10%. The patient received neoadjuvant vinorelbine-cisplatin chemotherapy followed by volumetric modulated arc therapy (VMAT) thoracic radiotherapy at 66 Gy, achieving clinical and radiological stabilization. This case highlights the occurrence of a second driver-negative primary lung adenocarcinoma in a non-smoker and underscores the importance of integrated histopathological, immunohisto chemical, and targeted molecular evaluation in distinguishing primary tumors from metastases, as well as the potential role of post-therapeutic carcinogenesis.