ArticleBreast cancer research : BCR2021
Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions.
Article 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 It has been retracted, and should not be counted. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Optical coherence tomography angiography measurements in tamoxifen associated retinopathy: a systematic review and meta-analysis.BMC ophthalmology · 2025Pooled it
- RET receptor tyrosine kinase promotes breast cancer metastasis to the brain and RET inhibitors pralsetinib and selpercatinib suppress breast cancer brain metastases.Cell death & disease · 2026Article
- Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis.Cancer research · 2026Article
- HMC3 revealed: how much do these "Microglia" really tell us?Frontiers in immunology · 2026Review
- Palliative care in patients with brain metastases from breast cancer: a qualitative descriptive study of attitudes, practices, and barriers.BMC palliative care · 2025Article
- Decoding the mechanisms underlying breast cancer brain metastasis: paving the way for precision therapeutics.Biomarker research · 2025Review
- A silence catalyst: CCL5-mediated intercellular communication in cancer.Archives of toxicology · 2025Review
- Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.Journal of translational medicine · 2025Review
- 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
- Interaction between Estrogen Receptors and p53: A Broader Role for Tamoxifen?Endocrinology · 2025Review
- The immune landscape in brain metastasis.Neuro-oncology · 2025Review
- Review
- Sex bias in tumor immunity: insights from immune cells.Theranostics · 2025Review
- Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.Cancer biology & therapy · 2024Review
- STAT3: Key targets of growth-promoting receptor positive breast cancer.Cancer cell international · 2024Review
- The complexity of immune evasion mechanisms throughout the metastatic cascade.Nature immunology · 2024Review
- Protecting the Brain: Novel Strategies for Preventing Breast Cancer Brain Metastases through Selective Estrogen Receptor β Agonists and In Vitro Blood-Brain Barrier Models.International journal of molecular sciences · 2024Article
- The Role of Microglia in Brain Metastases: Mechanisms and Strategies.Aging and disease · 2024Review
- Harnessing immunotherapy for brain metastases: insights into tumor-brain microenvironment interactions and emerging treatment modalities.Journal of hematology & oncology · 2023Review
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
Corrections and comments
- Retraction · 2025-05-12Concerns/Issues about Image · Duplication of/in Image · Error in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Objections by Author(s) · Original Data and/or Images not Provided and/or not Available · Unreliable Data ·
- Retracted
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBrain metastasis of breast cancer exhibits exceedingly poor prognosis, and both triple negative (TN) and Her2
methodsTo examine the effect of estrogen on brain metastasis progression, nude mice were implanted with brain metastatic cells and treated with either estrogen supplement, tamoxifen, or ovariectomy for estrogen depletion. For clinical validation study, brain metastasis specimens from pre- and post-menopause breast cancer patients were examined for microglia polarization by immunohistochemistry. To examine the estrogen-induced M2 microglia polarization, microglia cells were treated with estrogen, and the M1/M2 microglia polarization was detected by qRT-PCR and FACS. The estrogen receptor-deficient brain metastatic cells, SkBrM and 231BrM, were treated with conditioned medium (CM) derived from microglia that were treated with estrogen in the presence or absence of tamoxifen. The effect of microglia-derived CM on tumor cells was examined by colony formation assay and sphere forming ability.
resultsWe found that M2 microglia were abundantly infiltrated in brain metastasis of pre-menopausal breast cancer patients. A similar observation was made in vivo, when we treated mice systemically with estrogen. Blocking of estrogen signaling either by tamoxifen treatment or surgical resection of mice ovaries suppressed M2 microglial polarization and decreased the secretion of C-C motif chemokine ligand 5, resulting in suppression of brain metastasis. The estrogen modulation also suppressed stemness in TNBC cells in vitro. Importantly, estrogen enhanced the expression of signal regulatory protein α on microglia and restricted their phagocytic ability.
conclusionsOur results indicate that estrogen promotes brain metastasis by skewing polarity of M2 microglia and inhibiting their phagocytic ability, while tamoxifen suppresses brain metastasis by blocking the M2 polarization of microglia and increasing their anti-tumor phagocytic ability. Our results also highlight a potential therapeutic utility of tamoxifen for treating brain metastasis of hormone receptor-deficient breast cancer.
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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.