Effects of Eribulin on Epithelial–Mesenchymal Plasticity in Patient-Derived Breast Cancer Cultures and Excised Tissues

BACKGROUND: The cytotoxic agent eribulin has been shown to promote EMT reversion, reduce treatment resistance, and potentially enhance responses to a range of therapeutic agents. METHODS: We examined the effects of eribulin in patient-derived breast cancer tissues and a phenotypically heterogeneous breast cancer cell line to assess EMT and chemotherapy response. RESULTS: Nanostring-based analysis of EMT-associated gene expression in breast cancers from patients receiving standard-of-care TAC neoadjuvant chemotherapy compared to a cohort receiving neoadjuvant eribulin (NeoEribulin trial) showed markedly reduced expression of EMT markers in cancers treated with eribulin versus TAC. Through single-cell immunofluorescent imaging and analysis, we identified that HCC38 triple-negative breast cancer (TNBC) cells exhibited a shift towards an epithelial-like state marked by E-cadherin upregulation following acute eribulin exposure, but not with other chemotherapeutic agents. Investigation of primary breast cancer cultures derived from pre-neoadjuvant biopsies also revealed that HER2-enriched primary breast cancer cells displayed heightened chemosensitisation to doxorubicin (Adriamycin), which was not recapitulated in TNBC cultures. CONCLUSIONS: Our data highlight the presence of contextual parameters which govern the degree of EMT regulation by eribulin.