Prospective Assessment of Systemic MicroRNAs as Markers of Response to Neoadjuvant Chemotherapy in Breast Cancer.

Andrew Mcguire,Nicola Miller,Ronan M Waldron,Olga Kalinina,Maire-Caitlin Casey,Aoife J Lowery,Maccon Keane,Helen Heneghan,Róisín M Dwyer,Michael J Kerin,Emma Holian,James A.L Brown,John Newell,Ailbhe Mcdermott

doi:10.3390/cancers12071820

Abstract

Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce tumour burden prior to surgical resection. However, only a subset of NACT treated patients will respond to treatment or achieve a pathologic complete response (pCR). This multicenter, prospective study (CTRIAL-IE (ICORG) 10-11 study) evaluated circulating microRNA as novel non-invasive prognostic biomarkers of NACT response in breast cancer. Selected circulating microRNAs (Let-7a, miR-21, miR-145, miR-155, miR-195) were quantified from patients undergoing standard of care NACT treatment (n = 114) from whole blood at collected at diagnosis, and the association with NACT response and clinicopathological features evaluated. NACT responders had significantly lower levels of miR-21 (p = 0.036) and miR-195 (p = 0.017), compared to non-responders. Evaluating all breast cancer cases miR-21 was found to be an independent predictor of response (OR 0.538, 95% CI 0.308–0.943, p < 0.05). Luminal cancer NACT responders were found to have significantly decreased levels of miR-145 (p = 0.033) and miR-21 (p = 0.048), compared to non-responders. This study demonstrates the prognostic ability of miR-21, miR-195 and miR-145 as circulating biomarkers stratifying breast cancer patients by NACT response, identifying patients that will derive the maximum benefit from chemotherapy.

Highlights

Adjuvant chemotherapy has been used in the management of breast cancer for several decades, and the current therapeutic protocols are dependent on the molecular subtype, disease stage and assessments of other clinicopathological factors influencing the potential for response
MiR-21 and miR-145 levels had significant variations in levels between responders compared to non-responders in the Luminal breast cancer subtype
MiRNAs have been shown as potential diagnostic biomarkers in breast cancer, with all selected targets in this study shown to be altered in breast cancer patients compared to controls

Summary

Introduction

Adjuvant chemotherapy has been used in the management of breast cancer for several decades, and the current therapeutic protocols are dependent on the molecular subtype, disease stage and assessments of other clinicopathological factors influencing the potential for response (such as age and health). Neoadjuvant chemotherapy (NACT) is used in locally advanced breast cancer to reduce the tumour burden prior to surgery, increasing the number of patients suitable for breast conserving surgery. It provides a unique opportunity for an in vivo assessment of how the tumour responds to chemotherapy. While studies have shown that pCR is associated with improved survival, this varies according to clinicopathological features and molecular subtype [1,2]. The majority of patients exhibit only a partial or poor response to NACT, and currently there is no reliable, clinically validated biomarker to help clinicians stratify patients that will respond

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