Evidence map›Paper›PMID 22010023›Full record

ReviewJournal of clinical oncology : official journal of the American Society of Clinical Oncology2011

Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer.

Todd W Miller, Justin M Balko, Carlos L Arteaga

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03192293 (Single Arm Phase 2 Study of Metformin and Simvastatin in Addition to Fulvestrant in Metastatic Estrogen Receptor Positive Breast Cancer), which is not on this map. Cited by 218 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
218citing papers in PubMed, 3 pooled it
15.4field-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.

NCT03192293 phase2unknown statusnot on this mapstarted 2017, after this paper: background citation

Single Arm Phase 2 Study of Metformin and Simvastatin in Addition to Fulvestrant in Metastatic Estrogen Receptor Positive Breast Cancer

TypeinterventionalSponsorNational University Hospital, SingaporeRan2017 to 2019Enrolled28ConditionsBreast CancerArmsMetformin/Simvastatin/Fulvestrant
3 · Its place in the literature

Who cites it

218 citing papers in PubMed, 3 syntheses or guidelines pooled it, 409 citations in OpenAlex.

  1. Pooled it
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  5. Overall Survival with Inavolisib inThe New England journal of medicine · 2025
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  8. Phase I/II Trial of Exemestane, Ribociclib, and Everolimus in Women with HRClinical cancer research : an official journal of the American Association for Cancer Research · 2021
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  19. Review
  20. Genetic Variation inInternational journal of molecular sciences · 2026
    Article

158 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

3 authors at 1 institution in 1 country.

Todd W MillerVanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA.
Justin M Balko
Carlos L Arteaga
Vanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7M
The effects of PTEN on tyrosine kinase signaling in breast cancerK99CA142899 · NCI · VANDERBILT UNIVERSITY · PI MILLER, TODD W. · 2010 to 2011
$282k
NCI NIH HHS K99 CA142899NCI NIH HHS K99CA142899NCI NIH HHS P30 CA068485NCI NIH HHS P30CA68485NCI NIH HHS P50 CA098131NCI NIH HHS P50CA98131
6 · The paper itself

Abstract

Although antiestrogen therapies targeting estrogen receptor (ER) α signaling prevent disease recurrence in the majority of patients with hormone-dependent breast cancer, a significant fraction of patients exhibit de novo or acquired resistance. Currently, the only accepted mechanism linked with endocrine resistance is amplification or overexpression of the ERBB2 (human epidermal growth factor receptor 2 [HER2]) proto-oncogene. Experimental and clinical evidence suggests that hyperactivation of the phosphatidylinositol 3-kinase (PI3K) pathway, the most frequently mutated pathway in breast cancer, promotes antiestrogen resistance. PI3K is a major signaling hub downstream of HER2 and other receptor tyrosine kinases. PI3K activates several molecules involved in cell-cycle progression and survival, and in ER-positive breast cancer cells, it promotes estrogen-dependent and -independent ER transcriptional activity. Preclinical tumor models of antiestrogen-resistant breast cancer often remain sensitive to estrogens and PI3K inhibition, suggesting that simultaneous targeting of the PI3K and ER pathways may be most effective. Herein, we review alterations in the PI3K pathway associated with resistance to endocrine therapy, the state of clinical development of PI3K inhibitors, and strategies for the clinical investigation of such drugs in hormone receptor-positive breast cancer.

Indexed as

Phosphoinositide-3 Kinase InhibitorsBreast NeoplasmsClinical Trials as TopicDrug Resistance, NeoplasmEstrogen Receptor ModulatorsFemaleHumansPhosphatidylinositol 3-KinasesProto-Oncogene MasReceptors, EstrogenSignal TransductionEstrogen Receptor ModulatorsMAS1 protein, humanPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene MasReceptors, Estrogen

Identifiers

PMID22010023
PMCPMC3221526
OpenAlexW2014001512

What Socratic holds

Textmetadata
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 Socratic graph.