Trial reportGenome medicine2018
Time series analysis of neoadjuvant chemotherapy and bevacizumab-treated breast carcinomas reveals a systemic shift in genomic aberrations.
Trial report in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00773695 (A Multicenter, Randomized, Phase II Clinical Trial to Evaluate the Effect of Avastin in Combination With Neoadjuvant Treatment Regimens on the Molecular and Metabolic Characteristics and Changes in the Primary Tumors With Reference to the Obtained Responses in Patients With Large Primary HER2 Negative Breast Cancers), which is not on this map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Phase II Clinical Trial to Evaluate the Effect of Avastin in Combination With Neoadjuvant Treatment Regimens on the Molecular and Metabolic Characteristics and Changes in the Primary Tumors With Reference to the Obtained Responses in Patients With Large Primary HER2 Negative Breast Cancers
Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- High mid-treatment tumour RNA disruption in patients with HER2-negative breast cancer is associated with improved disease-free survival after neoadjuvant chemotherapy.Breast cancer research : BCR · 2025Trial
- Protein Signature Predicts Response to Neoadjuvant Treatment With Chemotherapy and Bevacizumab in HER2-Negative Breast Cancers.JCO precision oncology · 2021Trial
- miRNA expression changes during the course of neoadjuvant bevacizumab and chemotherapy treatment in breast cancer.Molecular oncology · 2019Trial
- Molecular classification identifies aggressive gastrointestinal stromal tumor subtype targetable by PARP inhibitors.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- TMEM100 acts as a TAK1 receptor that prevents pathological cardiac hypertrophy progression.Cell communication and signaling : CCS · 2024Article
- An integrated omics approach highlights how epigenetic events can explain and predict response to neoadjuvant chemotherapy and bevacizumab in breast cancer.Molecular oncology · 2024Article
- Detection of transmembrane protein 100 in breast cancer: Correlation with malignant progression and chemosensitivity.CytoJournal · 2024Article
- Article
- CX3CL1 promotes cell sensitivity to ferroptosis and is associated with the tumor microenvironment in clear cell renal cell carcinoma.BMC cancer · 2022Article
- KMT2C is a potential biomarker of prognosis and chemotherapy sensitivity in breast cancer.Breast cancer research and treatment · 2021Article
- Genomic Analysis of Response to Neoadjuvant Chemotherapy in Esophageal Adenocarcinoma.Cancers · 2021Article
- The temporal mutational and immune tumour microenvironment remodelling of HER2-negative primary breast cancers.NPJ breast cancer · 2021Article
- Differences of Angiogenesis Factors in Tumor and Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Bevacizumab Plays a double-edged role in Neoadjuvant Therapy for Non-metastatic Breast Cancer: A Systemic Review and Meta-Analysis.Journal of Cancer · 2021Article
- DNA Damage and Activation of cGAS/STING Pathway Induce Tumor Microenvironment Remodeling.Frontiers in cell and developmental biology · 2021Review
- Targeting tumor cell-derived CCL2 as a strategy to overcome Bevacizumab resistance in ETV5Cell death & disease · 2020Article
- DNA Copy Number Variations as Markers of Mutagenic Impact.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemotherapeutic agents such as anthracyclines and taxanes are commonly used in the neoadjuvant setting. Bevacizumab is an antibody which binds to vascular endothelial growth factor A (VEGFA) and inhibits its receptor interaction, thus obstructing the formation of new blood vessels.
methodsA phase II randomized clinical trial of 123 patients with Her2-negative breast cancer was conducted, with patients treated with neoadjuvant chemotherapy (fluorouracil (5FU)/epirubicin/cyclophosphamide (FEC) and taxane), with or without bevacizumab. Serial biopsies were obtained at time of diagnosis, after 12 weeks of treatment with FEC ± bevacizumab, and after 25 weeks of treatment with taxane ± bevacizumab. A time course study was designed to investigate the genomic landscape at the three time points when tumor DNA alterations, tumor percentage, genomic instability, and tumor clonality were assessed. Substantial differences were observed with some tumors changing mainly between diagnosis and at 12 weeks, others between 12 and 25 weeks, and still others changing in both time periods.
resultsIn both treatment arms, good responders (GR) and non-responders (NR) displayed significant difference in genomic instability index (GII) at time of diagnosis. In the combination arm, copy number alterations at 25 loci at the time of diagnosis were significantly different between the GR and NR. An inverse aberration pattern was also observed between the two extreme response groups at 6p22-p12 for patients in the combination arm. Signs of subclonal reduction were observed, with some aberrations disappearing and others being retained during treatment. Increase in subclonal amplification was observed at 6p21.1, a locus which contains the VEGFA gene for the protein which are targeted by the study drug bevacizumab. Of the 13 pre-treatment samples that had a gain at VEGFA, 12 were responders. Significant decrease of frequency of subclones carrying gains at 17q21.32-q22 was observed at 12 weeks, with the peak occurring at TMEM100, an ALK1 receptor signaling-dependent gene essential for vasculogenesis. This implies that cells bearing amplifications of VEGFA and TMEM100 are particularly sensitive to this treatment regime.
conclusionsTaken together, these results suggest that heterogeneity and subclonal architecture influence the response to targeted treatment in combination with chemotherapy, with possible implications for clinical decision-making and monitoring of treatment efficacy.
trial registrationNCT00773695 . Registered 15 October 2008.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.