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

Abstract

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, 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.

Methods: This 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 dissemination: INSTIGO 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.

Keywords: RNA signature; TILs; blood cells; ctDNA; metastatic relapse; plasma proteins; predictive biomarker; triple negative breast cancer.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Veyssière, Lusho, Molnar, Kossai, Bernadach, Abrial, Bidet, Radosevic-Robin and Durando.

Figures

Figure 1

Design of the INSTIGO study. Patients will have blood samples taken at diagnosis, on the day of first-line surgery or post-NAC surgery, on the day of the start of radiotherapy, and 6 months and one year after radiotherapy. If necessary, a blood sample will be taken at the time of diagnosis of metastatic relapse. Blood samples will be used for circulating proteins quantification, blood cells assay and circulating tumour DNA quantification. In neoadjuvant setting, TILs rate will be evaluated from tumour tissue from the biopsy and from the operating room.