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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00815

Predictive and prognostic value of selected microRNAs in luminal breast cancer

Maria Amorim1, 2,  João Lobo1, 3, 4,  Mario Fontes-Sousa1, 5, Helena Estevão-Pereira1, 2, Paula Lopes1, 3,  Sofia Salta1, Nuno Coimbra1, 3, 4, Luís Antunes6, Susana Palma de Sousa5,  Rui Henrique1, 3, 4 and  Carmen Jeronimo1, 4*
  • 1IPO-Porto Research Centre, Portuguese Oncology Institute, Portugal
  • 2Abel Salazar Institute of Biomedical Sciences, University of Porto, Portugal
  • 3Department of Anatomical Pathology, Portuguese Oncology Institute, Portugal
  • 4Department of Pathology and Molecular Immunology, Abel Salazar Institute of Biomedical Sciences, University of Porto, Portugal
  • 5Department of Medical Oncology, Portuguese Oncology Institute, Portugal
  • 6Department of Epidemiology, Portuguese Oncology Institute, Portugal

Breast cancer (BrC) is the most frequent malignancy and the leading cause of cancer death among women worldwide. Approximately 70% of BrC are classified as luminal-like subtype, expressing the estrogen receptor. One of the most common and effective adjuvant therapies for this BrC subtype is endocrine therapy. However, its effectiveness is limited, with relapse occurring in up to 40% of patients. Because microRNAs have been associated with several mechanisms underlying endocrine resistance and sensitivity, they may serve as predictive and/or prognostic biomarkers in this setting.
Hence, the main goal of this study was to investigate whether miRNAs deregulated in endocrine-resistant BrC may be clinically relevant as prognostic and predictive biomarkers in luminal BrC patients treated with adjuvant endocrine therapy.
A global expression assay allowed for the identification of microRNAs differentially expressed between luminal patients with or without BrC recurrence after endocrine adjuvant therapy. Then, six microRNAs were chosen for validation using quantitative reverse transcription polymerase chain reaction in a larger set of tissue samples. Thus, miR-30c-5p, miR-30b-5p, miR-182-5p and miR-200b-3p were found to be independent predictors of clinical benefit from endocrine therapy. Moreover, miR-182-5p and miR-200b-3p displayed independent prognostic value for disease recurrence in luminal BrC patients after endocrine therapy.
Our results indicate that selected miRNAs may constitute clinically useful ancillary tools for management of luminal BrC patients. Nevertheless, additional validation, ideally in a multicentric setting is required to confirm support our findings.

Keywords: breast cancer, luminal subtype, Endocrine therapy, Endocrine resistance, biomarkers, MicroRNAs

Received: 16 Jan 2019; Accepted: 07 Aug 2019.

Copyright: © 2019 Amorim, Lobo, Fontes-Sousa, Estevão-Pereira, Lopes, Salta, Coimbra, Antunes, Palma de Sousa, Henrique and Jeronimo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Carmen Jeronimo, IPO-Porto Research Centre, Portuguese Oncology Institute, Porto, Portugal, carmenjeronimo@ipoporto.min-saude.pt