Evidence map›Paper›PMID 34392831›Full record

ReviewBreast cancer research : BCR2021

ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer.

Jamie O Brett, Laura M Spring, Aditya Bardia, Seth A Wander

Registry-linked trialOpen access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Breast cancer research : BCR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07753954 (Imaging to Re-evaluate Elacestrant Clinical Application), which is not on this map. Cited by 238 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
238citing papers in PubMed, 6 pooled it
45.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT07753954 phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

Imaging to Re-evaluate Elacestrant Clinical Application

TypeinterventionalSponsorJules Bordet InstituteRan2026 to 2031Enrolled160ConditionsER+ / HER2- Advanced Breast CancerArmsElacestrant
3 · Its place in the literature

Who cites it

238 citing papers in PubMed, 6 syntheses or guidelines pooled it, 387 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. SEOM-GEICAM-SOLTI clinical guidelines in advanced breast cancer (UPDATE 2025).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Guideline
  4. Pooled it
  5. Guideline
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative,Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
  19. Trial
  20. Article

178 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Jamie O BrettDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Laura M SpringHarvard Medical School, Boston, MA, USA.
Aditya BardiaHarvard Medical School, Boston, MA, USA.
Seth A WanderHarvard Medical School, Boston, MA, USA. swander@partners.org.
Massachusetts General Hospital · USCenter for Cancer Research · USHarvard University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In metastatic hormone receptor-positive breast cancer, ESR1 mutations are a common cause of acquired resistance to the backbone of therapy, estrogen deprivation by aromatase inhibition. How these mutations affect tumor sensitivity to established and novel therapies are active areas of research. These therapies include estrogen receptor-targeting agents, such as selective estrogen receptor modulators, covalent antagonists, and degraders (including tamoxifen, fulvestrant, and novel agents), and combination therapies, such as endocrine therapy plus CDK4/6, PI3K, or mTORC1 inhibition. In this review, we summarize existing knowledge surrounding the mechanisms of action of ESR1 mutations and roles in resistance to aromatase inhibition. We then analyze the recent literature on how ESR1 mutations affect outcomes in estrogen receptor-targeting and combination therapies. For estrogen receptor-targeting therapies such as tamoxifen and fulvestrant, ESR1 mutations cause relative resistance in vitro but do not clearly lead to resistance in patients, making novel agents in this category promising. Regarding combination therapies, ESR1 mutations nullify any aromatase inhibitor component of the combination. Thus, combinations using endocrine alternatives to aromatase inhibition, or combinations where the non-endocrine component is efficacious as monotherapy, are still effective against ESR1 mutations. These results emphasize the importance of investigating combinatorial resistance, challenging as these efforts are. We also discuss future directions and open questions, such as studying the differences among distinct ESR1 mutations, asking how to adjust clinical decisions based on molecular surveillance testing, and developing novel therapies that are effective against ESR1 mutations.

Indexed as

Antineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsCyclin-Dependent KinasesDrug Resistance, NeoplasmEstrogen Receptor alphaFemaleHumansMechanistic Target of Rapamycin Complex 1MutationPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsReceptors, EstrogenSelective Estrogen Receptor ModulatorsAntineoplastic Agents, HormonalAromatase InhibitorsBiomarkers, TumorCyclin-Dependent KinasesESR1 protein, humanEstrogen Receptor alphaMechanistic Target of Rapamycin Complex 1Phosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsReceptors, EstrogenSelective Estrogen Receptor ModulatorsBreast cancerCDK4/6CombinationESR1 mutationHormone receptor/estrogen receptorResistanceSERCASERDSERM

Identifiers

PMID34392831
PMCPMC8365900
OpenAlexW3193378962

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.