Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer.

Valentina K Todorova,Hunter Smith,Stephanie D Byrum,Allen J Gies,Nathan S Reyna,Cade Haynie,Issam Makhoul

doi:10.3390/curroncol29020055

Abstract

Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. Method: Plasma samples of 20 breast cancer patients treated with NACT were collected prior to and after the first cycle. RNA sequencing was used to determine microRNA profiling. The Cancer Genome Atlas (TCGA) was used to explore the expression patterns and survivability of the candidate miRNAs, and their potential targets based on the expression levels and copy number variation (CNV) data. Results: Three miRNAs before that NACT (miR-30b, miR-328 and miR-423) predicted pCR in all of the analyzed samples. Upregulation of miR-127 correlated with pCR in triple-negative breast cancer (TNBC). After the first NACT dose, pCR was predicted by exo-miR-141, while miR-34a, exo-miR182, and exo-miR-183 predicted non-pCR. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer.

Highlights

Breast cancer is the second leading cause of cancer death among women, with an annual increase rate of approximately 3% [1]
A total of 14 patients had estrogen receptor (ER) progesterone receptor (PR) positive and human epidermal growth factor receptor 2 (HER2) negative (ER+/PR+/Her2)-breast cancer, and 6 patients were diagnosed with triple-negative breast cancer (TNBC), including 3 patients with pathological complete response (pCR) and 3 patients with non-pCR
The results from this study suggest that significantly altered plasma exo-Micro RNAs (miRNAs) prior to and after the first cycle of Neoadjuvant chemotherapy (NACT) may potentially serve as minimally invasive predictors of pCR in breast cancer

Summary

Introduction

Breast cancer is the second leading cause of cancer death among women, with an annual increase rate of approximately 3% [1]. Achievement of pathologic complete response (pCR) in breast cancer patients receiving NACT is associated with both overall survival and disease-free survival [5]. The associations between the molecular profiles of breast tumors before the treatment and the response to chemotherapy have been examined in several studies [18,19]. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT. A significant correlation between the candidate miRNAs and the overall survival, subtype, and metastasis in breast cancer, suggesting their potential role as predictive biomarkers of pCR. Conclusions: If the miRNAs identified in this study are validated in a large cohort of patients, they might serve as predictive non-invasive liquid biopsy biomarkers for monitoring pCR to NACT in breast cancer

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