Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy

Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.