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ePoster Display

297P - Transcriptomic modification induced by the first cycle of neoadjuvant chemotherapy impacts response to treatment in triple-negative breast cancer (TNBC)

Date

16 Sep 2021

Session

ePoster Display

Topics

Targeted Therapy;  Pathology/Molecular Biology

Tumour Site

Breast Cancer

Presenters

Isabelle Desmoulins

Citation

Annals of Oncology (2021) 32 (suppl_5): S457-S515. 10.1016/annonc/annonc689

Authors

I. Desmoulins1, D. Chardin2, C. Richard3, L. Arnould4, R. Boidot3, O. Humbert2

Author affiliations

  • 1 Medical Oncology, Centre Georges-François Leclerc (Dijon), 21000 - Dijon/FR
  • 2 Département D'imagerie Médecine Nucléaire, Centre Antoine Lacassagne, 06000 - Nice/FR
  • 3 Molecular Biology Unit, Centre Georges-François Leclerc (Dijon), 21000 - Dijon/FR
  • 4 Département De Biologie Et De Pathologie Des Tumeurs, Centre Georges-François Leclerc, 21000 - Dijon/FR
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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.

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