Abstract 3331: An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer

Abstract

Abstract Introduction: The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer. Methods: Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or ALDH1+ phenotypes were determined by immunohistochemistry. Results: A higher proportion of CD44+/CD24- tumor cells and ALDH1 positivity in pre-chemotherapy biopsy was correlated with higher histologic grade, estrogen receptor negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. ALDH1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response (pCR) following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumor cells were significantly increased after PST. The cases with increased CD44+/CD24- tumor cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumor cell population after PST were associated with estrogen receptor negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs. Conclusions: The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumor progression, emphasizing the need for targeting of CSCs in the breast cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3331. doi:10.1158/1538-7445.AM2011-3331