Identification of DNA methylation biomarkers with potential to predict response to neoadjuvant chemotherapy in triple-negative breast cancer

Braydon Meyer,Alex Swarbrick,Susan J Clark,Clare Stirzaker,Ruth Pidsley,Beena Kumar,Kate Harvey,Samuel Clifton,Vinod Ganju,Dilys Lam,Nicola J Armstrong,Qian Du,Warwick Locke,Niantao Deng,Phuc-Loi Luu

doi:10.1186/s13148-021-01210-6

Abstract

Neoadjuvant chemotherapy (NAC) is used to treat triple-negative breast cancer (TNBC) prior to resection. Biomarkers that accurately predict a patient’s response to NAC are needed to individualise therapy and avoid chemotoxicity from unnecessary chemotherapy. We performed whole-genome DNA methylation profiling on diagnostic TNBC biopsy samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) NAC study. We found 9 significantly differentially methylated regions (DMRs) at diagnosis which were associated with response to NAC. We show that 4 of these DMRs are associated with TNBC overall survival (P < 0.05). Our results highlight the potential of DNA methylation biomarkers for predicting NAC response in TNBC.

Highlights

Triple-negative breast cancer (TNBC) represents ~ 15–20% of all breast cancers and compared with non-TNBC is associated with a higher risk of disease recurrence after treatment and shorter overall survival [1]
To identify if DNA methylation alterations are associated with Neoadjuvant chemotherapy (NAC) response, we performed a genome-wide methylation analysis of TNBC samples from the Sequential Evaluation of Tumours Undergoing Preoperative (SETUP) neoadjuvant clinical study [4]
Biopsies were (See figure on page.) Fig. 1 DNA methylation associated with response to NAC and patient survival in the SETUP study

Summary

Introduction

Triple-negative breast cancer (TNBC) represents ~ 15–20% of all breast cancers and compared with non-TNBC is associated with a higher risk of disease recurrence after treatment and shorter overall survival [1]. Neoadjuvant chemotherapy (NAC) is typically applied in the TNBC setting, and the degree of pathological response to NAC correlates with long-term prognosis [2]; 30–40% of TNBC patients achieve a pathological complete response (pCR), associated with a favourable. Epigenetic modifications of tumour DNA, including DNA methylation, are showing widespread promise as molecular biomarkers of disease and treatment response. We aimed to identify a DNA methylation signature in tumours predictive of response to NAC in TNBC patients. Meyer et al Clinical Epigenetics (2021) 13:226

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