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Chemosensitivity to doxorubicin of ER-positive/HER2-negative breast cancers with high 21-gene recurrence score: A study based on in vitro chemoresponse assay.

 Sung Gwe Ahn  ;  Soong June Bae  ;  Changik Yoon  ;  Yoon Jin Cha  ;  Hak Woo Lee  ;  Seung Ah Lee  ;  Joon Jeong 
 PLoS One, Vol.12(11) : e0187679, 2017 
Journal Title
 PLoS One 
Issue Date
Adult ; Aged ; Antineoplastic Agents/pharmacology ; Biological Assay ; Biomarkers, Tumor/genetics* ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy* ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Death/drug effects ; Doxorubicin/pharmacology* ; Drug Resistance, Neoplasm/genetics* ; Estrogen Receptor alpha/genetics* ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Ki-67 Antigen/genetics ; Ki-67 Antigen/metabolism ; Middle Aged ; Neoplasm Grading ; Neoplasm Recurrence, Local/diagnosis ; Neoplasm Recurrence, Local/drug therapy* ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; Prognosis ; ROC Curve ; Receptor, ErbB-2/deficiency ; Receptor, ErbB-2/genetics* ; Tumor Cells, Cultured
AIM: The 21-gene recurrence score (RS) predicts a clinical benefit of chemotherapy for individuals with ER-positive/HER2-negative breast cancer. Using in vitro chemoresponse assay, we compared the chemosensitivity according to RS in these patients. METHOD: Among the patients with Oncotype Dx assay, we identified 63 patients who had chemotherapy response assays to doxorubicin based on adenosine triphosphate. The degree of chemosensitivity to doxorubicin was translated into the cell death rate (CDR). The RS was also dichotomized with a cutoff of 26. RESULTS: Of 63 patients, 34 (54%), 17 (27%), and 12 patients (19%) had a low, intermediate, and high RS, respectively. The mean CDR differed significantly according to categorized RS, with 17.3±10.8 in the low RS group vs. 23.6±16.3 in the intermediate RS group vs. 28.8±12.6 in the high RS group (P = 0.024, One-way ANOVA test). The mean CDR was significantly higher in the higher RS (26≥) group compared with the lower RS (<26) group (P = 0.025, the Student's t-test), as well as in the high RS (>30) group compared with the low RS (<18) group (P = 0.012, the Student's t-test). Also, continuous RS and CDR correlated positively (Pearson's R = 0.337; P = 0.007). High RS demonstrated the odds ratio (OR = 26.33; 95% CI = 1.69-410.0) for predicting tumors with chemosensitivity on the multivariate analysis. CONCLUSIONS: The chemosensitivity measured by in vitro chemoresponse assay was different according to the RS. Our findings support that tumors with high RS has the chemosensitivity even though they are luminal/HER2-negative tumors.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
Yonsei Authors
배숭준(Bae, Soong June)
안성귀(Ahn, Sung Gwe) ORCID logo https://orcid.org/0000-0002-8778-9686
윤창익(Yoon, Changik)
이학우(Lee, Hak Woo)
정준(Jeong, Joon) ORCID logo https://orcid.org/0000-0003-0397-0005
차윤진(Cha, Yoon Jin) ORCID logo https://orcid.org/0000-0002-5967-4064
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