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

Lee HE, Kim JH, Kim YJ, Choi SY, Kim SW, Kang E, Chung IY, Kim IA, Kim EJ, Choi Y, Ryu HS, Park SY - Br. J. Cancer (2011)

Bottom Line: The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST.Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Hospital, 28 Yeongon-dong, Jongno-gu, Seoul 110-744, Korea.

ABSTRACT

Background: 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 with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.

Results: A higher proportion of CD44+/CD24- tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24- tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER 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, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.

Conclusion: The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.

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Related in: MedlinePlus

Changes of putative CSC populations after primary systemic therapy (PST) in the cases not achieving pathologic complete response. CD44+/CD24− tumour cell proportions (A) and ALDH1+ tumour cell grades (B) increased significantly after PST in total. Within the subgroup receiving AD regimen (C and D), CD44+/CD24− tumour cell proportions increased significantly (C) and the grades of ALDH1+ tumour cells showed a tendency to increase after PST (D). In the subgroup treated with AC regimen (E and F), only grades of ALDH1+ tumour cells increased after PST with a marginal significance (F). AD=doxorubicin plus docetaxel; AC=doxorubicin plus cyclophosphamide.
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fig2: Changes of putative CSC populations after primary systemic therapy (PST) in the cases not achieving pathologic complete response. CD44+/CD24− tumour cell proportions (A) and ALDH1+ tumour cell grades (B) increased significantly after PST in total. Within the subgroup receiving AD regimen (C and D), CD44+/CD24− tumour cell proportions increased significantly (C) and the grades of ALDH1+ tumour cells showed a tendency to increase after PST (D). In the subgroup treated with AC regimen (E and F), only grades of ALDH1+ tumour cells increased after PST with a marginal significance (F). AD=doxorubicin plus docetaxel; AC=doxorubicin plus cyclophosphamide.

Mentions: We assessed changes of CD44+/CD24− and ALDH1+ tumour cell populations before and after PST in the 79 patients who did not achieve pCR. Both CD44+/CD24− tumour cell proportions and grades of ALDH1+ tumour cells significantly increased after PST (P=0.013 and P=0.018, respectively) (Figures 2A, B and 3). Within the subgroup receiving AD regimen, CD44+/CD24− tumour cell proportions also increased significantly (P=0.017) and the grades of ALDH1+ tumour cells had a tendency to increase after PST (P=0.098). In the subgroup treated with AC regimen, grades of ALDH1+ tumour cells increased after PST with a marginal significance (P=0.059) (Figures 2C–F). Also, we investigated whether the changes of putative CSC population after PST varied according to breast cancer subtype. There were increasing trends of the putative CSC populations after PST regardless of the breast cancer subtype, and especially, grades of ALDH1+ tumour cells were significantly increased after PST in HER2+ subtype (P=0.034) (Table 3).


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

Lee HE, Kim JH, Kim YJ, Choi SY, Kim SW, Kang E, Chung IY, Kim IA, Kim EJ, Choi Y, Ryu HS, Park SY - Br. J. Cancer (2011)

Changes of putative CSC populations after primary systemic therapy (PST) in the cases not achieving pathologic complete response. CD44+/CD24− tumour cell proportions (A) and ALDH1+ tumour cell grades (B) increased significantly after PST in total. Within the subgroup receiving AD regimen (C and D), CD44+/CD24− tumour cell proportions increased significantly (C) and the grades of ALDH1+ tumour cells showed a tendency to increase after PST (D). In the subgroup treated with AC regimen (E and F), only grades of ALDH1+ tumour cells increased after PST with a marginal significance (F). AD=doxorubicin plus docetaxel; AC=doxorubicin plus cyclophosphamide.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111169&req=5

fig2: Changes of putative CSC populations after primary systemic therapy (PST) in the cases not achieving pathologic complete response. CD44+/CD24− tumour cell proportions (A) and ALDH1+ tumour cell grades (B) increased significantly after PST in total. Within the subgroup receiving AD regimen (C and D), CD44+/CD24− tumour cell proportions increased significantly (C) and the grades of ALDH1+ tumour cells showed a tendency to increase after PST (D). In the subgroup treated with AC regimen (E and F), only grades of ALDH1+ tumour cells increased after PST with a marginal significance (F). AD=doxorubicin plus docetaxel; AC=doxorubicin plus cyclophosphamide.
Mentions: We assessed changes of CD44+/CD24− and ALDH1+ tumour cell populations before and after PST in the 79 patients who did not achieve pCR. Both CD44+/CD24− tumour cell proportions and grades of ALDH1+ tumour cells significantly increased after PST (P=0.013 and P=0.018, respectively) (Figures 2A, B and 3). Within the subgroup receiving AD regimen, CD44+/CD24− tumour cell proportions also increased significantly (P=0.017) and the grades of ALDH1+ tumour cells had a tendency to increase after PST (P=0.098). In the subgroup treated with AC regimen, grades of ALDH1+ tumour cells increased after PST with a marginal significance (P=0.059) (Figures 2C–F). Also, we investigated whether the changes of putative CSC population after PST varied according to breast cancer subtype. There were increasing trends of the putative CSC populations after PST regardless of the breast cancer subtype, and especially, grades of ALDH1+ tumour cells were significantly increased after PST in HER2+ subtype (P=0.034) (Table 3).

Bottom Line: The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST.Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University Hospital, 28 Yeongon-dong, Jongno-gu, Seoul 110-744, Korea.

ABSTRACT

Background: 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 with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24- or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.

Results: A higher proportion of CD44+/CD24- tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24- and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24- tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER 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, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.

Conclusion: The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.

Show MeSH
Related in: MedlinePlus