Abstract P2-26-23: Transcriptomic modification induced by the first cycle of neoadjuvant chemotherapy impacts response to treatment in triple negative breast cancer (TNBC)
Authors: Desmoulins Isabelle , Chardin David , Richard Corentin , Arnould Laurent , COCHET ALEXANDRE , Humbert Olivier , Boidot Romain 
Published: March 2023

Abstract
Background Despite adequate neoadjuvant chemotherapy, TNBC remains poor prognosis. Non-responding patient have 25-40% risk of relapse at 5 years. pCR is therefore currently considered as a major goal in TNBC and new tools of early prediction of residual disease should be identified. TransTep is a phase 2 monocentric clinical trial which aims to identify transcriptomic profile of triple-negative cancer cells associated with early tumor chemoresistance, as identified by FDG PET after the first course of neoadjuvant chemotherapy. Twenty patients were included between January 2015 and October 2017, with stage II or III of the UICC classification (except stage T4d). All patients received neoadjuvant chemotherapy with anthracyclines and taxanes sequentially, none of them had a dose-dense chemotherapy. Six patients obtained metabolic response (Delta SUV &lt; -30%) after one cycle of anthracycline. Methods Total RNA was extracted from biopsies (HES &gt; 30%) and used to prepare libraries thanks to TruSeq RNA library Prep kit (Illumina) and sequenced on NextSeq500 device. Results Transcriptomic expression analysis between tumors before chemotherapy and tumors after one course of chemotherapy showed that tumors showing a significant decrease of their Delta SUV (←30%) had a much higher gene expression variation than tumors with a Delta SUV &gt;-30%. These tumors presented, after one course of chemotherapy, a decrease of cell cycle, DNA replication and Fanconi anemia pathway related genes, while they harbored an increase of genes belonging to immunity related pathways such as natural killer cell mediated toxicity, TH17 cell differentiation, or chemokine signaling pathway. As patients had a surgery after neoadjuvant chemotherapy, we had Chevalier tumor response. As observed with FDG PET data, patients with a good response according to Chevalier (class 1) criteria presented a much higher transcriptomic modification after one course of chemotherapy. Patients with a little gene expression modification were classified as Chevalier 3. When we focused on pathways impacted by chemotherapy in tumors classified as Chevalier 1, we observed a significant decrease of cell cycle, DNA replication and DNA repair pathways related gene after one course of chemotherapy, whereas a high number of genes belonging to immunity related genes (NK cells, antigen processing and presentation, or chemokine signaling pathway) were increased. Conclusion Our results tend to indicate that transcriptomic tumor response after one course of chemotherapy could forecast final response to treatment. Moreover, it seems that one cycle of anthracycline-based chemotherapy is able to get hot some breast tumors, and that this tumor warming could be a marker of good response to the full treatment. In the following months, we will test whether transcriptomic could predict progression free survival and/or overall survival of patients. We will also look for the best early marker of response between PET FDG and tumor transcriptomic modifications. Based on these results, a new trial will be organized. A therapeutic adaptation depending on the transcriptomic or metabolic data will be proposed to increase pCR rate and prognosis of patients. Moreover, with years and therapeutic innovations, patient managment obviously evolves. This was recently the case with a new standard of care in triple negative breast cancer with combination of platinum salt and immunotherapy. Therefore, a new trial, similar to TRANSTEP, will be carried out with this new standard of care.
Citation Format: Isabelle Desmoulins, David Chardin, Corentin Richard, Laurent Arnould, ALEXANDRE COCHET, Olivier Humbert, Romain Boidot. Transcriptomic modification induced by the first cycle of neoadjuvant chemotherapy impacts response to treatment in triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-23.