INSTIGO Trial: Evaluation of a Plasma Protein Profile as a Predictive Biomarker for Metastatic Relapse of Triple Negative Breast Cancer.

Hugo Veyssière,Sejdi Lusho,Catherine Abrial,Ioana Molnar,Xavier Durando,Yannick Bidet,Nina Radosevic-Robin,Myriam Kossai,Maureen Bernadach

doi:10.3389/fonc.2021.653370

Abstract

BackgroundTriple negative breast cancer (TNBC) accounts for 10-20% of breast cancers but has no specific therapy. While TNBC may be more sensitive to chemotherapy than other types of breast cancer, it has a poor prognosis. Most TNBC relapses occur during the five years following treatment, however predictive biomarkers of metastatic relapse are still lacking. High tumour-infiltrating lymphocytes (TILs) levels before and after neo-adjuvant chemotherapy (NAC) are associated with lower relapse risk and longer survival but TILs assessment is highly error-prone and still not introduced into the clinic. Therefore, having reliable biomarker of relapse, but easier to assess, remains essential for TNBC management. Searching for such biomarkers among serum/plasma proteins, circulating tumoral DNA (ctDNA) and blood cells appear relevant.MethodsThis single-centre and prospective study aims to discover predictive biomarkers of TNBC relapse and particularly focuses on plasma proteins. Blood samples will be taken at diagnosis, on the day of first-line or post-NAC surgery, on the day of radiotherapy start, then 6 months and one year after radiotherapy. A blood sample will be taken at the time of metastatic relapse diagnosis. Blood samples will be used for circulating protein quantification, blood cell counts and circulating tumour DNA quantification. A tumour RNA signature, based on the analysis of the RNA expression of 6 genes, will also be tested from the initial biopsy taken routinely. In NAC patients, TILs quantity will be assessed on TNBC pre-treatment biopsy and surgical specimen.Ethics and DisseminationINSTIGO belongs to category 2 interventional research on humans. This study has been approved by the SUD-EST IV ethics committee and is conducted in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study findings will be published in peer-reviewed medical journals.Clinical Trial Registration ClinicalTrials.gov, identifier NCT04438681.

Highlights

Triple negative breast cancer accounts for approximately 10-20% of breast cancers and is characterized by the lack -or by very low expression of oestrogen and progesterone receptors and the lack of amplification of the gene coding for HER2 (Human Epidermal Growth Factor Receptor 2) [1]
It has been shown that a high level of tumour-infiltrating lymphocytes (TILs) before and after neo-adjuvant chemotherapy (NAC) is associated with lower recurrence risk and longer recurrence-free survival [5, 6]
We propose to conduct a study that measures the concentrations of a set of plasma proteins to evaluate their ability to predict metastatic relapse in patients with Triple negative breast cancer (TNBC)

Summary

Background

Triple negative breast cancer (TNBC) accounts for 10-20% of breast cancers but has no specific therapy. While TNBC may be more sensitive to chemotherapy than other types of breast cancer, it has a poor prognosis. Most TNBC relapses occur during the five years following treatment, predictive biomarkers of metastatic relapse are still lacking. High tumour-infiltrating lymphocytes (TILs) levels before and after neo-adjuvant chemotherapy (NAC) are associated with lower relapse risk and longer survival but TILs assessment is highly error-prone and still not introduced into the clinic. Having reliable biomarker of relapse, but easier to assess, remains essential for TNBC management. Searching for such biomarkers among serum/plasma proteins, circulating tumoral DNA (ctDNA) and blood cells appear relevant

Methods

INTRODUCTION

Study Design

DISCUSSION

ETHICS STATEMENT