Locoregional event or dyssynchronous distant metastasis: clinicopathological and molecular analysis of contralateral axillary lymph node metastasis in breast cancer patients.

Aims: Contralateral axillary lymph node metastasis (CAM) is a rare clinical condition in patients with breast cancer (BC). CAM can be either a locoregional event or a distant metastasis. Molecular application for clonal evolution in BC has not been reported in CAM cases.

Methods: We studied six patients with CAM with clinical, pathological and/or molecular evidence of distant metastasis; those patients had poor outcomes.

Results: Two cases with molecular analysis of paired primary and CAM established clonal evolution of the CAM with its corresponding primary with additional molecular alteration, increased tumour mutation burden, and copy number variations (CNVs) in the CAMs. Four cases containing alterations from genes potentially modulate chromatin organization, supporting chromatin and subsequent transcriptional signature changes are essential in CAM. Molecular analysis is critical to establish the connection between CAM and its primary counterpart. Distant CAM shows clonal evolution compared with its corresponding primary with additional molecular alterations, increased mutation burden and/or copy number variations.

Conclusion: CAM should be evaluated individually and handled in a personalized fashion. Evidence of a true metastatic CAM can be supported by distant metastasis to other organs, specific morphological features and/or clonal evolution.