CD133 Is a Useful Surrogate Marker for Predicting Chemosensitivity to Neoadjuvant Chemotherapy in Breast Cancer

Abstract

BackgroundNeoadjuvant chemotherapy (NAC) is a standard care regimen for patients with breast cancer. However, the pathologic complete response (pCR) rate remains at 30%. We hypothesized that a cancer stem cell marker may identify NAC-resistant patients, and evaluated CD133 and ALDH1 as a potential surrogate marker for breast cancer. The aim of this study was to find a surrogate maker to predict chemosensitivity of NAC for breast cancer.Methodology/FindingsA total of 102 patients with breast cancer were treated with NAC consisting of epirubicin followed by paclitaxel. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity and prognostic potential of CD133 or ALDH1 expression was evaluated by immunohistochemistry. Clinical CR (cCR) and pCR rates were 18% (18/102) and 29% (30/102), respectively. Forty-seven (46%) patients had CD133-positive tumors before NAC, and CD133 expression was significantly associated with a low pCR rate (p = 0.035) and clinical non-responders. Multivariate analysis revealed that CD133 expression was significantly (p = 0.03) related to pCR. Recurrence was more frequent in patients with CD133-positive tumors (21/47, 45%) than that in patients with CD133-negative tumors (7/55, 13%). The number of patients with CD133-positive tumors (62%) after NAC was higher than that (46%) before NAC. Furthermore, most patients with CD133-positive tumors before NAC maintained the same status after NAC.Conclusion/SignificanceCD133 before NAC might be a useful marker for predicting the effectiveness of NAC and recurrence of breast cancer after NAC.

Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

“…In fact, CD133 expression was reported to be correlated with tumor recurrence in patients with breast cancer (74). In drug-sensitive MCF-7 cells, only a small fraction of cells was found to be CD133-positive (75).…”

CD133 as Biomarker in Breast Cancer

“…Recurrence was more frequent in patients with CD133+ tumors compared with CD133À, suggesting that CD133 may be a useful marker in predicting the effectiveness of NAC and recurrence of breast cancer (Aomatsu et al 2012). The numbers of CD44 high , CD24 low , and CD133+ cells in gemcitabine-, paclitaxel-, and 5-fluorouracil-resistant breast cancer lines, respectively, were higher compared with corresponding drugsensitive lines (Mine et al 2009).…”

“…Aomatsu N. et al examined the association between survival and the CD133 expression in patients with breast cancer treated with epirubicin followed by paclitaxel (Aomatsu et al 2012). DFS and OS in patients with CD133-positive tumors were significantly shorter than in patients with CD133-negative tumors prior to neoadjuvant therapy (NAC).…”

Anti-CSC Effects in Human Esophageal Squamous Cell Carcinomas and Eca109/9706 Cells Induced by Nanoliposomal Quercetin Alone or Combined with CD 133 Antiserum

“…However, it has been found in advanced study that prominin-1 CD133 also expressed in the prostate cancer, pancreatic cancer, breast cancer and colon cancer either as additional CSC marker or as prognostic marker (Aomatsu et al, 2012;Wang et al, 2012;Hori, 2013;Pellacani et al, 2013).…”