MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer.
miRNAs have been linked to chemosensitivity of breast cancer cells in vitro. In patients, however, there is no clinically validated method for predicting chemotherapy response. The aim of this study was to assess whether (I) a specific pattern of miRNA expression in pretherapeutic biopsies can predict response to neoadjuvant chemotherapy, and (II) differential miRNA expression in residual tumor after completion of chemotherapy allows further prognostic stratification of non-responding patients.



Sixty-four patients with newly diagnosed large (≥3 cm) or locally advanced primary breast cancers who underwent neoadjuvant anthracycline/taxane-based chemotherapy were included. Relative expression of 10 miRNAs likely to be associated with chemotherapy response (miR-7,-21,-29a,-29b,-34a,-125b,-155,-200c,-340,-451) was determined by quantitative RT-PCR from pretherapeutic biopsies (n = 64) and residual invasive tumor after chemotherapy (n = 42). Pathologic complete response (pCR) defined by absence of invasive tumor served as reference standard. In addition, miRNA expression was compared with disease-free and overall survival.



Nine (14%) of 64 patients achieved pCR. High expression of miR-7 and low expression of miR-340 in pretherapeutic biopsies predicted pCR with a negative predictive value of 96 and 97%, respectively (specificity 54 and 57%). The combined profile of miR-7high/miR-340lowdemonstrated improved specificity of 86% while maintaining a high negative predictive value (96%) to identify non-responders. Pretherapeutic expression of miR-200c and miR-155 showed prognostic information, and low expression was associated with increased overall survival (115 vs. 90 months, p ≤ 0.03). After chemotherapy, the overall survival of patients with residual invasive tumor was better for those demonstrating low miR-7 or high miR-125b (p = 0.01).



Intratumoral expression of miR-7 and miR-340 prior to neoadjuvant chemotherapy could be used to predict pCR and a profile of miR-7lowor miR-340highidentified patients unlikely to achieve pCR who might benefit from alternative treatment options including earlier surgery. Our study identifies miRNAs as promising predictive biomarkers, which could aid in optimization of breast cancer management and treatment stratification.
Institute of Pathology, Technische Universität München, Munich, Germany.|Division of Molecular Oncology, Center for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Mithu
M
Raychaudhuri
Department of Obstetrics and Gynecology, Technische Universität München, Munich, Germany.
Holger
H
Bronger
Institute of Pathology, Technische Universität München, Munich, Germany.
Theresa
T
Buchner
Department of Obstetrics and Gynecology, Technische Universität München, Munich, Germany.
Marion
M
Kiechle
Institute of Pathology, Technische Universität München, Munich, Germany.
Wilko
W
Weichert
Institute of Pathology, Technische Universität München, Munich, Germany. stefanie.avril@case.edu.|Department of Pathology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center, Wolstein Research Building, Room 65242103, Cornell Road, Cleveland, OH, 44106-7288, USA. stefanie.avril@case.edu.
Stefanie
0000-0002-3394-8733
S
Avril
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D035683:MicroRNAs; C570046:MIRN340 microRNA, human; C549242:MIRN7-1 microRNA, human
Breast cancer; Neoadjuvant chemotherapy; Prediction of response; Treatment response; miR-340; miR-7; miRNA