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MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer

  • Clinical trial
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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-340low demonstrated 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).

Conclusions

Intratumoral expression of miR-7 and miR-340 prior to neoadjuvant chemotherapy could be used to predict pCR and a profile of miR-7low or miR-340high identified 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.

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Acknowledgements

This study was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) Grant No SA1698/1-2 awarded to SA. MR was supported by a fellowship of the Technische Universität München. SA is supported by the Clinical and Translational Science Collaborative of Cleveland (KL2TR000440) from the National Center for Advancing Translational Sciences (NCATS) component of the NIH.

Author contributions

S.A. conceived of the study. S.A., M.R., and H.B. analyzed and interpreted data. S.A., M.R. and T.B. carried out experiments. H.B. provided study material and clinical follow-up data. W.W. and M.K. participated in data interpretation. All authors were involved in writing the paper and had final approval of the submitted and published versions.

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Author notes

  1. Marion Kiechle

    Present address: Division of Molecular Oncology, Center for DNA Fingerprinting and Diagnostics, Hyderabad, India

  2. Stefanie Avril

    Present address: 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

Authors and Affiliations

  1. Institute of Pathology, Technische Universität München, Munich, Germany

    Mithu Raychaudhuri, Theresa Buchner, Wilko Weichert & Stefanie Avril

  2. Department of Obstetrics and Gynecology, Technische Universität München, Munich, Germany

    Holger Bronger & Marion Kiechle

  3. Division of Molecular Oncology, Center for DNA Fingerprinting and Diagnostics, Hyderabad, India

    Mithu Raychaudhuri

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  1. Mithu Raychaudhuri
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Correspondence to Stefanie Avril.

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The authors declare that they have no conflict of interest.

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All procedures performed involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Mithu Raychaudhuri and Holger Bronger have contributed equally to this work.

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Raychaudhuri, M., Bronger, H., Buchner, T. et al. MicroRNAs miR-7 and miR-340 predict response to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res Treat 162, 511–521 (2017). https://doi.org/10.1007/s10549-017-4132-9

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  • DOI: https://doi.org/10.1007/s10549-017-4132-9

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