Abstract 297P
Background
Despite adequate neoadjuvant chemotherapy, TNBC remains of poor prognosis. Non-responding patient have a 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 profiles 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 < -50%) after one cycle of anthracycline.
Methods
Total RNA was extracted from biopsies (HES > 30%) and used to prepare libraries using the TruSeq RNA library Prep kit (Illumina) and sequenced on NextSeq500 device.
Results
Transcriptomic expression analysis between tumors before and tumors after one course of chemotherapy showed that 43 genes (belonging to 5 different pathways) were significantly impacted: FANCI, BLM, BRIP1, RAD51C, SLX4, APITD1, C19ORF40, FANCA (Fanconi Anemia pathway), RBL2, CDKN2D, CCNB1, CDKN2B, WEE1, TFDP1, MDM2, ATM, TTK, MCM6, CDC25C, BUB1 (Cell Cycle pathway) or RFC3, RFC4, RFC5, GTF2H3, MNAT1 (Nucleotide Excision Repair pathway) were decreased in good metabolic responders, whereas SHC3, KLRC2, KLRC3, KIR3DL2, PIK3CG, IFNG, ULBP2, PPP3CA, KLRK1, CASP3, PTK2B, FYN, SH2D1A (Natural killer cell mediated cytotoxicity pathway), and CREB1, IFNG, KLRC2, KLRC3, KLRC4, HSPA2, KIR3DL2, HLA-DOA, CTSS (Antigen processing and presentation pathway) were increased after one course of chemotherapy in same patients.
Conclusions
These first results need to be correlated with pCR data. In case of residual disease detection, a new trial that will allow therapeutic adaptation to the metabolic and transcriptomic data, and be able to increase pCR rate and disease prognosis.
Clinical trial identification
NCT02850302 August 1, 2016.
Editorial acknowledgement
Legal entity responsible for the study
Centre Georges-François Leclerc.
Funding
Has not received any funding.
Disclosure
L. Arnould: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca. R. Boidot: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Illumina; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. All other authors have declared no conflicts of interest.