Abstract 169P
Background
This study aimed to explore potential indicators associated with neoadjuvant efficacy of TCbHP regime (taxane, carboplatin, trastuzumab and pertuzumab) in HER2+ breast cancer.
Methods
LC-MS and GC-MS platform-based untargeted metabolomics were performed to determine the metabolic profiles of plasma samples from HER2+ breast cancer patients, who received and completed neoadjuvant therapy (NAT) with TCbHP regime and subsequent surgery at Chongqing University Cancer Hospital. Random forest (RF) was used to establish predictive models based on pre-therapeutic metabolic traits. Transcriptome analysis was performed in available samples to identify differentially expressed genes (DEGs) before treatment. Metabolic and transcriptomic data were integrated to uncover significantly perturbed pathways potentially involved in drug resistance.
Results
From July 20, 2020 to May 28, 2021, a total of 40 HER2+ breast cancer patients with 120 plasma samples were eligible and recruited for this study. Of whom 21 (52.5%) patients achieved pCR and 19 (47.5%) achieved non-pCR. There were significant differences in plasma metabolic profiles between non-pCR and pCR groups before and during treatment. A total of 100 differential metabolites were identified between pCR and non-pCR patients at pre-therapeutic period, which were significantly enriched in 40 metabolic pathways. Four key metabolites [sophorose, N-(2-acetamido)iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] were selected by RF analysis. The AUC value to discriminate pCR and non-PCR group to NAT of the single potential metabolite or combined panel of these metabolites were more than 0.910. 18 metabolites had potential value in monitoring effect. A total of 163 DEGs were identified between biopsy tissue samples from pCR and non-pCR patients. 39 altered pathways aberrantly expressed at both metabolic and transcriptional levels.
Conclusions
Metabolomics integrated with transcriptomics analysis could assist for gaining more insights into biochemical pathophysiology and facilitate the development of novel therapeutic targets for insensitive patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJZD-K202000104); Chongqing Science and Health Joint Medical Research Project (Grant No.2021MSXM085, 2021MSXM291, 2022MSXM004); Talent Program of Chongqing (Grant No. CQYC20200303137). Beijing Science and Technology Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJZD-K202000104); Chongqing Science and Health Joint Medical Research Project (Grant No.2021MSXM085, 2021MSXM291, 2022MSXM004); Talent Program of Chongqing (Grant No. CQYC20200303137); Beijing Science and Technology Innovation Medical Development Foundation (Grant No. KC2021-JF-0167-05).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
207P - Palbociclib (P) in patients (pts) with solid tumors with CDK4 or CDK6 amplification (amp): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study
Presenter: Maged Khalil
Session: Poster session 01
208P - Identification of BCOR mutation as a novel predictor of immunotherapy efficacy in gastrointestinal tumors
Presenter: Wuping Wang
Session: Poster session 01
209P - Molecular atlas of copy number variation(CNV) in lung cancer with brain metastases
Presenter: Xianfeng Zhang
Session: Poster session 01
210P - Lung tumour vascularity is a risk factor for survival in NSCLC patients undergoing surgery
Presenter: Andrea Riccardo Filippi
Session: Poster session 01
211P - Cost-efficient detection of NTRK1, NTRK2 and NTRK3 gene rearrangements using the test for 5’/3’-end unbalanced expression: The analysis of 8075 patients
Presenter: Evgeny Imyanitov
Session: Poster session 01
212P - Extracellular vesicle miRNA as effective biomarkers for predicting antitumor efficacy in lung adenocarcinoma treated with chemotherapy and checkpoint blockade
Presenter: Si Sun
Session: Poster session 01
213P - Unlocking cancer treatment opportunities by population-based advanced diagnostics in Norway
Presenter: Hege Russnes
Session: Poster session 01
214P - PESSA: A shiny app for pathway enrichment score-based survival analysis in cancer
Presenter: Ying Shi
Session: Poster session 01
215P - Identifying predictors of overall survival among TMB-low cancer patients treated with immune checkpoint inhibitors
Presenter: Camila Xavier
Session: Poster session 01
216P - PTCH1 mutation as a potential predictor of immune checkpoint inhibitors in gastrointestinal cancer
Presenter: Yang Tang
Session: Poster session 01