ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy-Resistant Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03820830 (A Phase III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer), which is not on this map. Cited by 95 papers, 1 of them a synthesis 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 III Open-label, Multicenter, Randomized Trial of Adjuvant Palbociclib in Combination With Endocrine Therapy Versus Endocrine Therapy Alone for Patients With Hormone Receptor Positive / HER2-negative Resected Isolated Locoregional Recurrence of Breast Cancer
Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Cyclin-dependent kinase 4 and 6 inhibitors in combination with neoadjuvant endocrine therapy in estrogen receptor-positive early breast cancer: a systematic review and meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial.Nature communications · 2026Trial
- Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Trial
- Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Dalpiciclib plus chidamide in HR + /HER2-advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial.Nature communications · 2026Article
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- Bazedoxifene and Beyond: Identifying This SERM's Targets and Deciphering Its Molecular Mechanisms.Advances in pharmacological and pharmaceutical sciences · 2026Review
- AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance.Science advances · 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
- Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.Breast cancer research : BCR · 2025Article
- A high-throughput platform for single-molecule tracking identifies drug interaction and cellular mechanisms.eLife · 2025Article
- PKMYT1 Is a Marker of Treatment Response and a Therapeutic Target for CDK4/6 Inhibitor-Resistance in ER+ Breast Cancer.Molecular cancer therapeutics · 2024Article
- Oral Estrogen Receptor PROTAC Vepdegestrant (ARV-471) Is Highly Efficacious as Monotherapy and in Combination with CDK4/6 or PI3K/mTOR Pathway Inhibitors in Preclinical ER+ Breast Cancer Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- CDKL3 is a targetable regulator of cell cycle progression in cancers.The Journal of clinical investigation · 2024Article
- Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537SResearch square · 2024Article
- Targeting Unique Ligand Binding Domain Structural Features Downregulates DKK1 in Y537SbioRxiv : the preprint server for biology · 2024Article
- Metastatic ER+ Breast Cancer: Mechanisms of Resistance and Future Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer.Cancer research · 2023Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeEndocrine therapy, using tamoxifen or an aromatase inhibitor, remains first-line therapy for the management of estrogen receptor (ESR1)-positive breast cancer. However, ESR1 mutations or other ligand-independent ESR1 activation mechanisms limit the duration of response. The clinical efficacy of fulvestrant, a selective estrogen receptor downregulator (SERD) that competitively inhibits agonist binding to ESR1 and triggers receptor downregulation, has confirmed that ESR1 frequently remains engaged in endocrine therapy-resistant cancers. We evaluated the activity of a new class of selective estrogen receptor modulators (SERM)/SERD hybrids (SSH) that downregulate ESR1 in relevant models of endocrine-resistant breast cancer. Building on the observation that concurrent inhibition of ESR1 and the cyclin-dependent kinases 4 and 6 (CDK4/6) significantly increased progression-free survival in advanced patients, we explored the activity of different SERD- or SSH-CDK4/6 inhibitor combinations in models of endocrine therapy-resistant ESR1(+) breast cancer. EXPERIMENTAL
designSERDs, SSHs, and the CDK4/6 inhibitor palbociclib were evaluated as single agents or in combination in established cellular and animal models of endocrine therapy-resistant ESR1(+) breast cancer.
resultsThe combination of palbociclib with a SERD or an SSH was shown to effectively inhibit the growth of MCF7 cell or ESR1-mutant patient-derived tumor xenografts. In tamoxifen-resistant MCF7 xenografts, the palbociclib/SERD or SSH combination resulted in an increased duration of response as compared with either drug alone.
conclusionsA SERD- or SSH-palbociclib combination has therapeutic potential in breast tumors resistant to endocrine therapies or those expressing ESR1 mutations. See related commentary by DeMichele and Chodosh, p. 4999.
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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 Socratic graph.