Gefitinib in breast cancer: molecular rationale, clinical evidence, resistance mechanisms and future perspectives

Breast cancer continues to be the most prevalent malignancy and a major cause of cancer mortality among women worldwide. Targeted therapies improved outcomes, but therapeutic resistance and disease progression remain major challenges, especially in triple-negative breast cancer (TNBC). Gefitinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR), approved for EGFR-mutated non-small cell lung cancer (NSCLC), has demonstrated only limited clinical activity in unselected breast cancer populations despite promising preclinical activity. This review critically evaluates the role of EGFR in breast cancer, the pharmacology of gefitinib and evidence from preclinical and clinical studies. It discusses concepts such as molecular profiling, targeted drug delivery and highlights biomarker-guided patient selection, mechanisms of resistance and rational combination strategies. These results support testing gefitinib as a precision medicine strategy in certain breast cancer cases, although clinical testing is needed.