Expression of breast cancer stem cell markers as predictors of prognosis and response to trastuzumab in HER2-positive breast cancer.
Breast cancer stem cells (BCSCs) have been suggested to have clinical implications for cancer therapeutics because of their proposed role in chemoresistance. The aim of this study was to investigate the impact of BCSC marker expression on clinical outcome and trastuzumab response in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.



We analysed the expression of BCSC markers, CD44+/CD24- and aldehyde dehydrogenase 1 (ALDH1), and clinical outcomes in three sets of breast cancer cases: Set 1, 242 HER2-positive primary breast cancers treated by various modalities; Set 2, 447 HER2-positive primary breast cancers treated with surgery and chemotherapy plus adjuvant trastuzumab; Set 3, 112 metastatic HER2-positive breast cancers treated with trastuzumab.



Expression of CD44+/CD24- and ALDH1 was detected in 30.7% and 10.0%, respectively, of the Set 1 cases, and was associated with hormone receptor negativity. In survival analyses, expression of CD44+/CD24-, but not ALDH1, was found to be an independent prognostic factor for poor disease-free and overall survival in whole patients and also in the subgroup not receiving adjuvant trastuzumab. In Set 2 cases treated with adjuvant trastuzumab, CD44+/CD24- expression was an independent prognostic factor for poor disease-free survival, but not for overall survival; expression of ALDH1 had no impact on disease-free or overall survival. In metastatic disease treated with trastuzumab (Set 3 cases), CD44+/CD24- and ALDH1 expression had no effect on trastuzumab response or survival.



These results suggest that the CD44+/CD24- phenotype can be used as a prognostic factor for clinical outcome and a predictive factor of trastuzumab response in patients with HER2-positive primary breast cancer.
Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.|Department of Pathology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842, Korea.
An Na
AN
Seo
Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.|Department of Pathology, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
Hee Jin
HJ
Lee
Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.
Eun Joo
EJ
Kim
Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.
Min Hye
MH
Jang
Department of Medical Oncology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.|Department of Medical Oncology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
Yu Jung
YJ
Kim
Department of Medical Oncology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.|Department of Medical Oncology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
Jee Hyun
JH
Kim
Department of Surgery, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.|Department of Surgery, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
Sung-Won
SW
Kim
Department of Pathology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
Han Suk
HS
Ryu
Department of Pathology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
In Ae
IA
Park
Department of Medical Oncology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
Seock-Ah
SA
Im
Department of Pathology, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
Gyungyub
G
Gong
Department of Medical Oncology, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
Kyung Hae
KH
Jung
Department of Surgery, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
Hee Jeong
HJ
Kim
Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.|Department of Pathology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
So Yeon
SY
Park
D000080924:Aldehyde Dehydrogenase 1 Family; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D016019:Survival Analysis; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
D000080924:Aldehyde Dehydrogenase 1 Family; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases; D050697:Retinal Dehydrogenase; D000068878:Trastuzumab; C497889:CD24 protein, human; C497483:CD44 protein, human; C510223:ALDH1A1 protein, human; C508053:ERBB2 protein, human