TY - JOUR
T1 - Dynamic changes in CD44v-positive cells after preoperative anti-HER2 therapy and its correlation with pathologic complete response in HER2-positive breast cancer
AU - Yamauchi, Teruo
AU - Fernandez, Jose Rodrigo Espinosa
AU - Imamura, Chiyo K.
AU - Yamauchi, Hideko
AU - Jinno, Hiromitsu
AU - Takahashi, Maiko
AU - Kitagawa, Yuko
AU - Nakamura, Seigo
AU - Lim, Bora
AU - Krishnamurthy, Savitri
AU - Reuben, James M.
AU - Liu, Diane
AU - Tripathy, Debasish
AU - Chen, Helen
AU - Takebe, Naoko
AU - Saya, Hideyuki
AU - Ueno, Naoto T.
N1 - Funding Information:
Advanced Clinical Research Organization (ACRO) for the support in fund operation for the international collaboration.
Funding Information:
1Division of Medical Oncology, St. Luke’s International Hospital, Tokyo, Japan 2Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 3Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School of Medicine, Tokyo, Japan 4Department of Breast Surgery, St. Luke’s International Hospital, Tokyo, Japan 5Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan 6Department of Surgery, Keio University School of Medicine, Tokyo, Japan 7Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan 8Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 9Department of Hematopathology Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 10Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 11Cancer Therapy Evaluation Program, National Cancer Institute, Rockville, MD, USA 12Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan
Funding Information:
This study was supported by funding from the Japan Medical Association with the Ministry of Health, Labor and Welfare, MD Anderson Sister Institution Network Fund, GlaxoSmithKline, and is the first independent NCI CTEP-sponsored investigator-initiated trial conducted in Japan (NCT01688609). Lapatinib is an asset of Novartis Pharma AG as of March 2, 2015.
Publisher Copyright:
© Yamauchi et al.
PY - 2018
Y1 - 2018
N2 - Chemotherapy has been reported to increase the proportion of cancer stem cells (CSCs) and to promote epithelial-mesenchymal transition (EMT) phenotype changes. Anti-HER2 therapy may provide a strategy for eliminating CSC and EMT, which contribute to therapeutic resistance. No study has determined the changes in the quantity or characteristics of CSCs or circulating tumor cells (CTCs) with EMT phenotype during preoperative anti-HER2 therapy, and whether these changes correlate to response to dual anti-HER2 therapy. In a prospective clinical trial to evaluate pharmacodynamic biomarkers, 18 patients with operable primary HER2-positive breast cancer received dual anti-Her2 preoperative therapy with trastuzumab and lapatinib with paclitaxel. Proportions of tumor cells with CSC characteristics and EMT markers in CTC's were estimated at baseline, after 6 and 18 weeks of preoperative therapy to determine the quantitative cutoff value to predict pathologic complete response (pCR). Out of 18 patients, 8 (44%) had a pCR; 5 of these 8 patients (62%) were positive for CD44v at baseline and none were positive on the 6-week biopsy. In contrast, 6 of the 10 patients without pCR exhibited persistent levels, or enrichment of CD44v proportion and expression at 6 and 18 weeks (p=0.0128). Other biomarkers were not statistically significant predictors of pCR. Enrichment of CD44v-positive tumor cells after dual anti-HER2 therapy alone may predict poor response to dual anti-HER2 therapy plus chemotherapy.
AB - Chemotherapy has been reported to increase the proportion of cancer stem cells (CSCs) and to promote epithelial-mesenchymal transition (EMT) phenotype changes. Anti-HER2 therapy may provide a strategy for eliminating CSC and EMT, which contribute to therapeutic resistance. No study has determined the changes in the quantity or characteristics of CSCs or circulating tumor cells (CTCs) with EMT phenotype during preoperative anti-HER2 therapy, and whether these changes correlate to response to dual anti-HER2 therapy. In a prospective clinical trial to evaluate pharmacodynamic biomarkers, 18 patients with operable primary HER2-positive breast cancer received dual anti-Her2 preoperative therapy with trastuzumab and lapatinib with paclitaxel. Proportions of tumor cells with CSC characteristics and EMT markers in CTC's were estimated at baseline, after 6 and 18 weeks of preoperative therapy to determine the quantitative cutoff value to predict pathologic complete response (pCR). Out of 18 patients, 8 (44%) had a pCR; 5 of these 8 patients (62%) were positive for CD44v at baseline and none were positive on the 6-week biopsy. In contrast, 6 of the 10 patients without pCR exhibited persistent levels, or enrichment of CD44v proportion and expression at 6 and 18 weeks (p=0.0128). Other biomarkers were not statistically significant predictors of pCR. Enrichment of CD44v-positive tumor cells after dual anti-HER2 therapy alone may predict poor response to dual anti-HER2 therapy plus chemotherapy.
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U2 - 10.18632/oncotarget.23914
DO - 10.18632/oncotarget.23914
M3 - Article
AN - SCOPUS:85040915684
VL - 9
SP - 6872
EP - 6882
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 6
ER -