Trial reportBreast cancer research : BCR2014
Phosphorylated p-70S6K predicts tamoxifen resistance in postmenopausal breast cancer patients randomized between adjuvant tamoxifen versus no systemic treatment.
Trial report in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- The Prognostic Role of Ribosomal Protein S6 Kinase 1 Pathway in Patients With Solid Tumors: A Meta-Analysis.Frontiers in oncology · 2019Pooled it
- P-mTOR Expression and Implication in Breast Carcinoma: A Systematic Review and Meta-Analysis.PloS one · 2017Pooled it
- PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane.Journal of cancer research and clinical oncology · 2020Trial
- PIK3CA mutations, phosphatase and tensin homolog, human epidermal growth factor receptor 2, and insulin-like growth factor 1 receptor and adjuvant tamoxifen resistance in postmenopausal breast cancer patients.Breast cancer research : BCR · 2014Trial
- MAPK signaling mediates tamoxifen resistance in estrogen receptor-positive breast cancer.Molecular and cellular biochemistry · 2025Review
- Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort.British journal of cancer · 2024Article
- Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities.Molecular therapy oncolytics · 2023Review
- IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer.International journal of cancer · 2020Article
- Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2020Article
- Body fatness and mTOR pathway activation of breast cancer in the Women's Circle of Health Study.NPJ breast cancer · 2020Article
- Cancer-immune interactions in ER-positive breast cancers: PI3K pathway alterations and tumor-infiltrating lymphocytes.Breast cancer research : BCR · 2019Article
- Dissecting the predictive value of MAPK/AKT/estrogen-receptor phosphorylation axis in primary breast cancer to treatment response for tamoxifen over exemestane: a Translational Report of the Intergroup Exemestane Study (IES)-PathIES.Breast cancer research and treatment · 2019Article
- Hierarchical clustering of activated proteins in the PI3K and MAPK pathways in ER-positive, HER2-negative breast cancer with potential therapeutic consequences.British journal of cancer · 2018Article
- Mitotic count can predict tamoxifen benefit in postmenopausal breast cancer patients while Ki67 score cannot.BMC cancer · 2018Article
- The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors.BMC cancer · 2018Article
- Hyperactive mTOR and MNK1 phosphorylation of eIF4E confer tamoxifen resistance and estrogen independence through selective mRNA translation reprogramming.Genes & development · 2017Article
- Increased MAPK1/3 Phosphorylation in Luminal Breast Cancer Related with PIK3CA Hotspot Mutations and Prognosis.Translational oncology · 2017Article
- Enrichment of PI3K-AKT-mTOR Pathway Activation in Hepatic Metastases from Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Differential effects of rapalogues, dual kinase inhibitors on human ovarian carcinoma cells in vitro.International journal of oncology · 2016Article
- Immunohistochemical prediction of lapatinib efficacy in advanced HER2-positive breast cancer patients.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionActivation of the phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways results in anti-estrogen resistance in vitro, but a biomarker with clinical validity to predict intrinsic resistance has not been identified. In metastatic breast cancer patients with previous exposure to endocrine therapy, the addition of a mammalian target of rapamycine (mTOR) inhibitor has been shown to be beneficial. Whether or not patients on adjuvant endocrine treatment might benefit from these drugs is currently unclear. A biomarker that predicts intrinsic resistance could potentially be used as companion diagnostic in this setting. We tested the clinical validity of different downstream-activated proteins in the PI3K and/or MAPK pathways to predict intrinsic tamoxifen resistance in postmenopausal primary breast cancer patients.
methodsWe recollected primary tumor tissue from patients who participated in a randomized trial of adjuvant tamoxifen (1-3 years) versus observation. After constructing a tissue micro-array, cores from 563 estrogen receptor α positive were immunostained for p-AKT(Thr308), p-AKT(Ser473), p-mTOR, p-p706SK and p-ERK1/2. Cox proportional hazard models for recurrence free interval were used to assess hazard ratios and interactions between these markers and tamoxifen treatment efficacy.
resultsInteractions were identified between tamoxifen and p-AKT(Thr308), p-mTOR, p-p70S6K and p-ERK1/2. Applying a conservative level of significance, p-p70S6K remained significantly associated with tamoxifen resistance. Patients with p-p70S6K negative tumors derived significant benefit from tamoxifen (HR 0.24, P < 0.0001), while patients whose tumor did express p-p70S6K did not (HR = 1.02, P =0.95), P for interaction 0.004. In systemically untreated breast cancer patients, p-p70S6K was associated with a decreased risk for recurrence.
conclusionsPatients whose tumor expresses p-p70S6K, as a marker of downstream PI3K and/or MAPK pathway activation, have a favorable prognosis, but do not benefit from adjuvant tamoxifen. A potential benefit from inhibitors of the PI3K/Akt/mTOR pathway in these patients needs to be further explored.
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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.