Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients

A. Giordano, H. Gao, E. N. Cohen, S. Anfossi, J. Khoury, K. Hess, S. Krishnamurthy, S. Tin, M. Cristofanilli, G. N. Hortobagyi, W. A. Woodward, A. Lucci, J. M. Reuben*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: Cancer stem cells (CSCs) are epithelial tumor cells that express CD44+CD24-/lo. CSCs can be further divided into those that have aldehyde dehydrogenase (ALDH) activity (Aldefluor+) and those that do not. We hypothesized that if CSCs are responsible for tumor dissemination, their presence in bone marrow (BM) would be prognostic in early stages of breast cancer (EBC) patients. Patients and methods: BM aspirates were collected at the time of surgery from 108 patients with EBC. BM was analyzed for CSCs and ALDH activity by flow cytometry. Overall survival and disease-free survival (DFS) were calculated from the date of diagnosis and analyzed with Kaplan-Meier survival plots. Cox multivariate proportional hazards model was also carried out. Results: Patients with CSCs in BM had a hazard ratio (HR) of 8.8 for DFS (P = 0.002); patients with Aldefluor+ CSCs had a HR of 5.9 (P = 0.052) for DFS. All deceased patients (n = 7) had CSCs in BM. In multivariate analysis, the presence of CSCs in BM was a prognostic factor of DFS (HR = 15.8, P = 0.017). Conclusions: The presence of BM metastasis is correlated with CSCs and these CSCs irrespective of ALDH activity are an independent adverse prognostic factor in EBC patients.

Original languageEnglish (US)
Pages (from-to)2515-2521
Number of pages7
JournalAnnals of Oncology
Volume24
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • Bone marrow
  • Breast cancer
  • Cancer stem cells
  • Cd24
  • Cd44
  • Circulating tumor cells

ASJC Scopus subject areas

  • Hematology
  • Oncology

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