Heparanase: a potential marker of worse prognosis in estrogen receptor-positive breast cancer

Tamar Zahavi, Mali Salmon-Divon, Roberto Salgado, Michael Elkin, Esther Hermano, Ariel M. Rubinstein, Prudence A. Francis, Angelo Di Leo, Giuseppe Viale, Evandro de Azambuja, Lieveke Ameye, Christos Sotiriou, Asher Salmon, Nataly Kravchenko-Balasha, Amir Sonnenblick

Research output: Contribution to journalArticlepeer-review


Heparanase promotes tumor growth in breast tumors. We now evaluated heparanase protein and gene-expression status and investigated its impact on disease-free survival in order to gain better insight into the role of heparanase in ER-positive (ER+) breast cancer prognosis and to clarify its role in cell survival following chemotherapy. Using pooled analysis of gene-expression data, we found that heparanase was associated with a worse prognosis in estrogen receptor-positive (ER+) tumors (log-rank p < 10−10) and predictive to chemotherapy resistance (interaction p = 0.0001) but not hormonal therapy (Interaction p = 0.62). These results were confirmed by analysis of data from a phase III, prospective randomized trial which showed that heparanase protein expression is associated with increased risk of recurrence in ER+ breast tumors (log-rank p = 0.004). In vitro experiments showed that heparanase promoted tumor progression and increased cell viability via epithelial–mesenchymal transition, stemness, and anti-apoptosis pathways in luminal breast cancer. Taken together, our results demonstrated that heparanase is associated with worse outcomes and increased cell viability in ER+ BC.

Original languageEnglish
Article number67
Journalnpj Breast Cancer
Issue number1
Publication statusPublished - Dec 2021

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)


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