Immunohistochemical Detection of Breast Cancer Stem Cells in Hormone Receptor-Positive Breast Cancer and Their Role in Response to Endocrine Therapy and Clinical Outcome

Background: Breast cancer stem cells are rich in triple negative or human epidermal growth factor receptor-2-positive breast cancers. The role of these stem cells in hormone receptor-positive breast cancers is unknown. Therefore, we launched this retrospective biomarker analysis to clarify the role of stem cells in relation with endocrine therapy in hormone receptor-positive breast cancer. Methods: Formalin-fixed paraffin-embedded tissue samples from primary stage IV, hormone receptor-positive breast cancers prior to endocrine therapy were obtained from 4 cancer centers in Japan between 1999 and 2008. We examined the expression of ALDH1 and CD44/CD24 in breast tissue and correlated the results with response to endocrine therapy and patient prognosis. Results: ALDH1-positive and CD44(+)CD24(-)cancer cells were found in 16% of 92 samples and 27% of 77 samples, respectively. Response to endocrine therapy was similar in the ALDH1-positive and ALDH1-negative tumor groups, and between CD44(+)CD24(-) and other tumor groups. After a median follow-up period of 793 days, neither ALDH1 positivity nor CD44(+)CD24(-) status of tumor cells was related to progression-free survival (ALDH1 positive vs. negative, 378 vs. 292 days, p = 0.53; CD44(+)CD24(-) vs. others, 224 vs. 269 days, p = 0.52) or overall survival (ALDH1 positive vs. negative, 1,348 vs. 1,479 days, p = 0.17; CD44(+)CD24(-) vs. others, 1,071 vs. 1,462 days, p = 0.54). Conclusions: There is no correlation between biomarker expression and outcome in hormone receptor-positive breast cancer.