Tumour microenvironment and HER2-low status dictate response and resistance to anthracycline-taxane chemotherapy in premenopausal TNBC: a retrospective multicohort study

Our findings reveal that an immune-poor tumour microenvironment and HER2-low biology are key, complementary determinants of intrinsic resistance to standard chemotherapy in premenopausal TNBC. These readily available biomarkers provide a mechanistic rationale for patient stratification, suggesting that sTIL-low tumours might benefit from immunomodulatory strategies, while HER2-low tumours represent a candidate population for novel antibody-drug conjugates. This paradigm shift from empirical to biomarker-informed therapy could help overcome chemoresistance in this high-risk group.