ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.
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. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- 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
- Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas withBiomolecules & therapeutics · 2026Article
- Biomarkers of primary and secondary resistance to cyclin dependent kinases 4 and 6 inhibitors in metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer: a narrative review.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- 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
- ESR1 Y537S and D538G Mutations Drive Resistance to CDK4/6 Inhibitors in Estrogen Receptor-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- ctDNA-based liquid biopsy reveals wider mutational profile with therapy resistance and metastasis susceptibility signatures in early-stage breast cancer patients.The journal of liquid biopsy · 2025Article
- Real-world clinical multi-omics analyses reveal bifurcation of ER-independent and ER-dependent drug resistance to CDK4/6 inhibitors.Nature communications · 2025Article
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- ESR1 Fusions Invoke Breast Cancer Subtype-Dependent Enrichment of Ligand-Independent Oncogenic Signatures and Phenotypes.Endocrinology · 2024Article
- Genomic Landscape of Circulating Tumor DNA in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Treated With Abemaciclib: Data From the SCRUM-Japan Cancer Genome Screening Project.JCO precision oncology · 2024Article
- CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape.NPJ breast cancer · 2024Article
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10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe explored the clinical and genomic characteristics of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) after progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) ± endocrine therapy (ET) to understand potential resistance mechanisms that may aid in identifying treatment options. EXPERIMENTAL
designPatients in the United States with HR+, HER2- MBC had tumor biopsies collected from a metastatic site during routine care following progression on a CDK4 and 6i ± ET (CohortPost) or prior to initiating CDK4 and 6i treatment (CohortPre) and analyzed using a targeted mutation panel and RNA-sequencing. Clinical and genomic characteristics were described.
resultsThe mean age at MBC diagnosis was 59 years in CohortPre (n = 133) and 56 years in CohortPost (n = 223); 14% and 45% of patients had prior chemotherapy/ET, and 35% and 26% had de novo stage IV MBC, respectively. The most common biopsy site was liver (CohortPre, 23%; CohortPost, 56%). CohortPost had significantly higher tumor mutational burden (TMB; median 3.16 vs. 1.67 Mut/Mb, P < 0.0001), ESR1 alteration frequency (mutations: 37% vs. 10%, FDR < 0.0001; fusions: 9% vs. 2%, P = 0.0176), and higher copy-number amplification of genes on chr12q15, including MDM2, FRS2, and YEATS4 versus patients in the CohortPre group. In addition, CDK4 copy-number gain on chr12q13 was significantly higher in CohortPost versus CohortPre (27% vs. 11%, P = 0.0005).
conclusionsDistinct mechanisms potentially associated with resistance to CDK4 and 6i ± ET, including alterations in ESR1 and amplification of chr12q15 and CDK4 copy-number gain, were identified.
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