ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Genomic Complexity Predicts Resistance to Endocrine Therapy and CDK4/6 Inhibition in Hormone Receptor-Positive (HR+)/HER2-Negative Metastatic Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03007979 (A Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer), which is not on this map. Cited by 31 papers, 2 of them syntheses that pooled it.
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 Phase II Clinical Trial Assessing the Safety of an Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer
Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Circulating tumour DNA and its clinical relevance in predicting progression-free survival and overall survival in patients with advanced breast cancer: a systematic review and meta-analysis.Breast cancer research and treatment · 2026Pooled it
- CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates.Frontiers in immunology · 2026Pooled it
- Exploring the role of ESR1 mutations in metastatic hormone receptor-positive breast cancer T cell immune surveillance disruption.Breast cancer research : BCR · 2025Trial
- Elacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.Nature communications · 2024Trial
- Mutational Analysis of Circulating Tumor DNA in Patients With Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving Palbociclib: Results From the TREnd Trial.JCO precision oncology · 2024Trial
- CDKN1B inactivation impacts ER signaling and drives resistance to endocrine therapy in breast cancer.British journal of cancer · 2026Article
- Novel Insights into the Role of circRNAs in Cancer Immunotherapy Resistance and Clinical Implications.International journal of molecular sciences · 2026Review
- Article
- Prognostic Impact of Early Metabolic Response on Interim 18F-FDG PET/CT in HR+/HER2- Metastatic Breast Cancer Treated with CDK4/6 Inhibitors.Medicina (Kaunas, Lithuania) · 2026Article
- Concurrent genomic assessment of circulating tumour cells and ctDNA to guide therapy in metastatic breast cancer.BMC cancer · 2025Article
- Longitudinal profiling of hormone receptor positive, HER2 negative metastatic breast cancer through droplet digital PCR-based circulating tumor DNA fragmentomics.Translational oncology · 2025Article
- Homologous recombination repair gene alteration is strongly associated with more prostate-specific membrane antigen-positive metastases in newly diagnosed hormone-sensitive prostate cancer with ≤5 conventional imaging defined distant metastases.European journal of nuclear medicine and molecular imaging · 2025Article
- Circulating genomic landscape following cyclin-dependent kinase 4/6 inhibitors exposure in HR + /HER2- metastatic breast cancer: a retrospective multi-institutional Consortium analysis.NPJ breast cancer · 2025Article
- Clinical impact of single-gene vs. panel sequencing in advanced HR + /HER2- breast cancer: insights and implications.NPJ breast cancer · 2025Article
- Personalized ctDNA monitoring in metastatic HR+/HER2- breast cancer patients during endocrine and CDK4/6 inhibitor therapy.NPJ breast cancer · 2025Article
- APOBEC3 mutagenesis drives therapy resistance in breast cancer.Nature genetics · 2025Article
- Targeted degradation of CDK4/6 by LA-CB1 inhibits EMT and suppresses tumor growth in orthotopic breast cancer.Scientific reports · 2025Article
- Longitudinal Glioma Monitoring via Cerebrospinal Fluid Cell-Free DNA.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Molecular Basis of Breast Tumor Heterogeneity.Advances in experimental medicine and biology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeClinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance. EXPERIMENTAL
designctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole-exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome sequencing was performed at baseline and serial timepoints to assess blood copy-number burden (bCNB).
resultsHigh bTMB and bCNB were associated with lack of clinical benefit and significantly shorter progression-free survival (PFS) compared with patients with low bTMB or low bCNB (all P < 0.05). Dominant APOBEC signatures were detected at baseline exclusively in cases with high bTMB (5/13, 38.5%) versus low bTMB (0/37, 0%; P = 0.0006). Alterations in ESR1 were enriched in samples with high bTMB (P = 0.0005). There was a high correlation between bTMB determined by WES and bTMB determined using a 600-gene panel (R = 0.98). During serial monitoring, an increase in bCNB score preceded radiographic progression in 12 of 18 (66.7%) patients.
conclusionsGenomic complexity detected by noninvasive profiling of bTMB and bCNB predicted poor outcomes in patients treated with ET and CDK4/6i and identified early disease progression before imaging. Novel treatment strategies including immunotherapy-based combinations should be investigated in this population.
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Registered trials
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.