ArticleBreast cancer research and treatment2020
Pharmacokinetic and pharmacodynamic analysis of fulvestrant in preclinical models of breast cancer to assess the importance of its estrogen receptor-α degrader activity in antitumor efficacy.
Article in Breast cancer research and treatment, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 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.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- The Selective Estrogen Receptor Degrader ZN-c5 Has Broad Antitumor Activity in Wild-Type and Mutant ER-Positive Breast Cancer Models.Molecular cancer therapeutics · 2026Article
- Targeting the ERα DBD-LBD Interface with Mitoxantrone Disrupts Receptor Function through Proteasomal Degradation.Molecular cancer therapeutics · 2026Article
- Vitiligo Signature-Based Drug Screening Identifies Fulvestrant as a Novel Immunotherapy Combination Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Effect of Bazedoxifene and Fulvestrant for Preventing Ovarian Hyperstimulation Syndrome: An Experimental Study.Journal of clinical medicine · 2025Article
- Estrogen and glucocorticoid receptors co-regulate acrolein-induced respiratory and systemic homeostatic stress responses.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Increased Antiproliferative Activity of Antiestrogens and Neratinib Treatment by Calcitriol in HER2-Positive Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Imlunestrant a next-generation oral SERD overcomes ESR1 mutant resistance in estrogen receptor-positive breast cancer.JCI insight · 2025Article
- Article
- Single Dose of a Small Molecule Leads to Complete Regressions of Large Breast Tumors in Mice.ACS central science · 2025Article
- Imlunestrant Is an Oral, Brain-Penetrant Selective Estrogen Receptor Degrader with Potent Antitumor Activity in ESR1 Wild-Type and Mutant Breast Cancer.Cancer research · 2025Article
- Retinoic acid antagonizes estrogen signaling to maintain adult uterine cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting unique ligand binding domain structural features downregulates DKK1 in Y537S ESR1 mutant breast cancer cells.Breast cancer research : BCR · 2025Article
- The EstroGene2.0 database for endocrine therapy response and resistance in breast cancer.NPJ breast cancer · 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
- EstroGene2.0: A multi-omic database of response to estrogens, ER-modulators, and resistance to endocrine therapies in breast cancer.bioRxiv : the preprint server for biology · 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
- Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC.Communications biology · 2024Article
- Estrogen Receptor Alpha Mutations, Truncations, Heterodimers, and Therapies.Endocrinology · 2024Review
- The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance.Cancer research · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeFulvestrant is a selective estrogen receptor downregulator (SERD) that is approved for first- or second-line use as a single agent or in combination with cyclin dependent kinase or phosphatidylinositol 3-kinase inhibitors for the treatment of metastatic breast cancer. Fulvestrant exhibits exceptionally effective antitumor activity in preclinical models of breast cancer, a success that has been attributed to its robust SERD activity despite modest receptor downregulation in patient tumors. By modeling human exposures in animal models we probe the absolute need for SERD activity.
methodsThree xenograft models of endocrine therapy-resistant breast cancer were used to evaluate the efficacy of fulvestrant administered in doses historically used in preclinical studies in the field or by using a dose regimen intended to model clinical exposure levels. Pharmacokinetic and pharmacodynamic analyses were conducted to evaluate plasma exposure and intratumoral ER downregulation.
resultsA clinically relevant 25 mg/kg dose of fulvestrant exhibited antitumor efficacy comparable to the historically used 200 mg/kg dose, but at this lower dose it did not result in robust ER downregulation. Further, the antitumor efficacy of the lower dose of fulvestrant was comparable to that observed for other oral SERDs currently in development.
conclusionThe use of clinically unachievable exposure levels of fulvestrant as a benchmark in preclinical development of SERDs may negatively impact the selection of those molecules that are advanced for clinical development. Further, these studies suggest that antagonist efficacy, as opposed to SERD activity, is likely to be the primary driver of clinical response.
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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.