ArticleNPJ breast cancer2022
Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer.
Article in NPJ breast cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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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
24 citing papers in PubMed, 33 citations in OpenAlex.
- Identifying Locally Recurrent Versus Second Primary Breast Cancer: Genomic Versus Clinical Criteria from Carolina Breast Cancer Study Phase III.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Trial
- Short-duration preoperative endocrine therapy alters molecular profiles to predict favourable outcome in ER+/HER2+ early breast cancer: a POETIC translational study.EBioMedicine · 2025Trial
- Landscape of somatic genetic alterations and PAM50 intrinsic subtypes in breast cancer associated with germline pathogenic variants in DNA-repair genes.Journal of the National Cancer Institute · 2026Article
- TP53-META, a meta-analysis tool for comparative transcriptomics of TP53 dependency: examples from target silencing and liver fibrosis.BMC bioinformatics · 2026Article
- TP53 mutation is associated with shorter treatment duration with CDK4/6 inhibitors, but not with immune checkpoint inhibitors, in ER-positive/HER2-negative breast cancer: real-world perspective.Breast cancer research : BCR · 2026Article
- Distinct genomic and immunologic tumor evolution in germline TP53-driven breast cancers.Nature communications · 2026Article
- Article
- Genomic landscape, immune microenvironment and survival in male versus female breast cancer.ESMO open · 2026Article
- Mutant p53 binds and controls estrogen receptor activity to drive endocrine resistance in ovarian cancer.Genes & development · 2026Article
- Integrated lipidomics and network pharmacology analysis to determine how Gu Fu Sheng Capsule improves lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head.Journal of traditional and complementary medicine · 2025Article
- Review
- MicroRNA‑96 promotes the proliferation and migration of breast cancer cells by inhibiting Smad7 expression.Oncology letters · 2025Article
- Interaction between Estrogen Receptors and p53: A Broader Role for Tamoxifen?Endocrinology · 2025Review
- Real-world clinical multi-omics analyses reveal bifurcation of ER-independent and ER-dependent drug resistance to CDK4/6 inhibitors.Nature communications · 2025Article
- Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer.NPJ breast cancer · 2024Article
- CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape.NPJ breast cancer · 2024Article
- Immunomodulatory Activity and Its Mechanisms of Two Polysaccharides fromMolecules (Basel, Switzerland) · 2023Article
- Association ofmedRxiv : the preprint server for health sciences · 2023Article
- Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype.Nature communications · 2023Article
- Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Both TP53 and ESR1 mutations occur frequently in estrogen receptor positive (ER+) metastatic breast cancers (MBC) and their distinct roles in breast cancer tumorigenesis and progression are well appreciated. Recent clinical studies discovered mutual exclusivity between TP53 and ESR1 mutations in metastatic breast cancers; however, mechanisms underlying this intriguing clinical observation remain largely understudied and unknown. Here, we explored the interplay between TP53 and ESR1 mutations using publicly available clinical and experimental data sets. We first confirmed the robust mutational exclusivity using six independent cohorts with 1,056 ER+ MBC samples and found that the exclusivity broadly applies to all ER+ breast tumors regardless of their clinical and distinct mutational features. ESR1 mutant tumors do not exhibit differential p53 pathway activity, whereas we identified attenuated ER activity and expression in TP53 mutant tumors, driven by a p53-associated E2 response gene signature. Further, 81% of these p53-associated E2 response genes are either direct targets of wild-type (WT) p53-regulated transactivation or are mutant p53-associated microRNAs, representing bimodal mechanisms of ER suppression. Lastly, we analyzed the very rare cases with co-occurrences of TP53 and ESR1 mutations and found that their simultaneous presence was also associated with reduced ER activity. In addition, tumors with dual mutations showed higher levels of total and PD-L1 positive macrophages. In summary, our study utilized multiple publicly available sources to explore the mechanism underlying the mutual exclusivity between ESR1 and TP53 mutations, providing further insights and testable hypotheses of the molecular interplay between these two pivotal genes in ER+ MBC.
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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.