Primary breast cancer patients with high risk clinicopathologic features have high percentages of bone marrow epithelial cells with ALDH activity and CD44 +CD24 lo cancer stem cell phenotype

James M. Reuben, Bang Ning Lee, Hui Gao, Evan N. Cohen, Michel Mego, Antonio Giordano, Xuemei Wang, Ashutosh Lodhi, Savitri Krishnamurthy, Gabriel N. Hortobagyi, Massimo Cristofanilli, Anthony Lucci, Wendy A. Woodward

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Background: Cancer stem cells (CSCs) are purported to be epithelial tumour cells expressing CD44 +CD24 lo that exhibit aldehyde dehydrogenase activity (Aldefluor +). We hypothesised that if CSCs are responsible for tumour dissemination, disseminated cells in the bone marrow (BM) would be positive for putative breast CSC markers. Therefore, we assessed the presence of Aldefluor + epithelial (CD326 +CD45 dim) cells for the presence of the CD44 +CD24 lo phenotype in BM of patients with primary breast cancer (PBC). Methods: BM aspirates were collected at the time of surgery from 66 patients with PBC. Thirty patients received neoadjuvant chemotherapy (NACT) prior to aspiration. BM was analysed for Aldefluor + epithelial cells with or without CD44 +CD24 lo expression by flow cytometry. BM aspirates from three healthy donors (HD) were subjected to identical processing and analyses and served as controls. Results: Patients with triple-receptor-negative (TN) tumours had a significantly higher median percentage of CD44 +CD24 lo CSC within Aldefluor + epithelial cell population than patients with other immunohistochemical subtypes (P = 0.018). Patients with TN tumours or with pN2 or higher pathologic nodal status were more likely to have a proportion of CD44 +CD24 lo CSC within Aldefluor + epithelial cell population above the highest level of HD. Furthermore, patients who received NACT were more likely to have percentages of Aldefluor + epithelial cells than the highest level of HD (P = 0.004). Conclusion: The percentage of CD44 +CD24 lo CSC in the BM is higher in PBC patients with high risk tumour features. The selection or enrichment of Aldefluor + epithelial cells by NACT may represent an opportunity to target these cells with novel therapies.

Original languageEnglish (US)
Pages (from-to)1527-1536
Number of pages10
JournalEuropean Journal of Cancer
Volume47
Issue number10
DOIs
StatePublished - Jul 2011

Keywords

  • Breast cancer stem cells
  • Disseminated tumour cells
  • Neoadjuvant chemotherapy
  • Triple-receptor negative

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Reuben, J. M., Lee, B. N., Gao, H., Cohen, E. N., Mego, M., Giordano, A., Wang, X., Lodhi, A., Krishnamurthy, S., Hortobagyi, G. N., Cristofanilli, M., Lucci, A., & Woodward, W. A. (2011). Primary breast cancer patients with high risk clinicopathologic features have high percentages of bone marrow epithelial cells with ALDH activity and CD44 +CD24 lo cancer stem cell phenotype. European Journal of Cancer, 47(10), 1527-1536. https://doi.org/10.1016/j.ejca.2011.01.011