Reduction of CD44(+)/CD24(-) breast cancer cells by conventional cytotoxic chemotherapy

Hum Pathol. 2010 Apr;41(4):574-81. doi: 10.1016/j.humpath.2009.08.023. Epub 2009 Dec 11.


Breast cancer cells with the CD44(+)/CD24(-) phenotype have been associated with stem cell properties. To analyze effects of cytotoxic chemotherapy on these cells, we examined a series of 50 breast carcinomas before and after neoadjuvant chemotherapy with epirubicin/cyclophosphamide using double immunofluorescence. Before treatment, an average of 4.4% of the tumor cells displayed a CD44(+)/CD24(-) phenotype. However, after chemotherapy, the frequency of CD44(+)/CD24(-) cells dropped to 2% (P = .008). To test this unexpected finding, we analyzed a second collective of 16 patients that preoperatively had received either 4 cycles of doxorubicin/pemetrexed, followed by 4 cycles of docetaxel or 4 cycles of doxorubicin/cyclophosphamide, followed by 4 cycles of docetaxel with similar results (8.7% CD44(+)/CD24(-) cells on average before and 1.1% after chemotherapy). In addition, no association was observed between the frequency of CD44(+)/CD24(-) cells and the response to chemotherapy or patient survival. However, patients with tumors containing high numbers of CD44(+)/CD24(-) cells more frequently developed bone metastases in the course of disease. In conclusion, our findings challenge the proposed role of CD44(+)/CD24(-) cells as cancer stem cells in tumor resistance to chemotherapy as they apparently are not selected by conventional cytotoxic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • CD24 Antigen / metabolism*
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Fluorescent Antibody Technique
  • Glutamates / administration & dosage
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Middle Aged
  • Neoadjuvant Therapy
  • Pemetrexed
  • Taxoids / administration & dosage


  • CD24 Antigen
  • Glutamates
  • Hyaluronan Receptors
  • Taxoids
  • Pemetrexed
  • Docetaxel
  • Epirubicin
  • Guanine
  • Doxorubicin
  • Cyclophosphamide