Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers.
OBJECTIVE
Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro, but their clinical significance remains to be clarified. The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers.


METHODS
Primary breast cancer patients (n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44(+)/CD24(-) tumor cells or ALDH1-positive tumor cells were considered stem cells.


RESULTS
Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44(+)/CD24(-) tumor cell proportions and pCR rates. Changes in the proportion of CD44(+)/CD24(-) or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR. The proportion of ALDH1-positive tumor cells increased significantly (P < 0.001) after neoadjuvant chemotherapy, but that of CD44(+)/CD24(-) tumor cells did not.


CONCLUSIONS
Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44(+)/CD24(-), play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker than CD44(+)/CD24(-) for the identification of breast cancer stem cells in terms of resistance to chemotherapy.
Tanei
Tomonori
T
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Morimoto
Koji
K
Shimazu
Kenzo
K
Kim
Seung Jin
SJ
Tanji
Yoshio
Y
Taguchi
Tetsuya
T
Tamaki
Yasuhiro
Y
Noguchi
Shinzaburo
S
D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis*; D000080924:Aldehyde Dehydrogenase 1 Family; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis*; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*; D050697:Retinal Dehydrogenase; D000097382:CD68 Molecule
D000444:Aldehyde Dehydrogenase; D000080924:Aldehyde Dehydrogenase 1 Family; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D000972:Antineoplastic Agents, Phytogenic; D051927:CD24 Antigen; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D015251:Epirubicin; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D019394:Ki-67 Antigen; D017239:Paclitaxel; D050697:Retinal Dehydrogenase; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C510223:ALDH1A1 protein, human