ArticlePloS one2019
Expression of HIF-1α is related to a poor prognosis and tamoxifen resistance in contralateral breast cancer.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
- Breast cancer hypoxia in relation to prognosis and benefit from radiotherapy after breast-conserving surgery in a large, randomised trial with long-term follow-up.British journal of cancer · 2022Trial
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- Article
- Hypoxia-inducible factors in breast cancer: prognostic indicators and emerging biomarkers: narrative review.Annals of medicine and surgery (2012) · 2025Review
- A lipid metabolism-related gene signature predicts prognosis after tamoxifen treatment in ER + breast cancer and reflects tumor microenvironment heterogeneity through single-cell analysis.BMC medical genomics · 2025Article
- Targeting EPAS-1/HIF-2α Pathway to Address Endocrine Resistance in Luminal A Type Breast Cancer.Translational oncology · 2025Article
- High hypoxia inducible factor-1α expression is associated with reduced survival in patients with breast cancer: A meta-analysis.World journal of clinical oncology · 2025Article
- Unveiling GBE1 as a hypoxia-related prognostic gene with significant impact on immune cell infiltration in HER2-enriched breast cancer.Discover oncology · 2025Article
- Modulating the tumor microenvironment in a mouse model of colon cancer using a combination of HIF-1α inhibitors and Toll-Like Receptor 7 agonists.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Hi-C profiling in tissues reveals 3D chromatin-regulated breast tumor heterogeneity informing a looping-mediated therapeutic avenue.Cell reports · 2025Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- 2-methoxyestradiol sensitizes tamoxifen-resistant MCF-7 breast cancer cells via downregulating HIF-1α.Medical oncology (Northwood, London, England) · 2024Article
- HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma.Cell death discovery · 2024Article
- Prognostic implications of TOR1B expression across cancer types: a focus on basal-like breast cancer and cellular adaptations to hypoxia.Journal of cancer research and clinical oncology · 2024Article
- Analyses of hypoxia-related risk factors and clinical relevance in breast cancer.Frontiers in oncology · 2024Article
- Therapeutic targeting of nuclear export and import receptors in cancer and their potential in combination chemotherapy.IUBMB life · 2024Review
- Hypoxia-induced epigenetic regulation of breast cancer progression and the tumour microenvironment.Frontiers in cell and developmental biology · 2024Review
- Deep learning and transfer learning identify breast cancer survival subtypes from single-cell imaging data.Communications medicine · 2023Article
- The role of mitochondrial/metabolic axis in development of tamoxifen resistance in breast cancer.Human cell · 2023Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdjuvant endocrine treatment improves survival after estrogen receptor (ER) positive breast cancer. Recurrences occur, and most patients with metastatic breast cancer develop treatment resistance and incurable disease. An influential factor in relation to endocrine treatment resistance is tumor hypoxia and the hypoxia inducible transcription factors (HIFs). Poor perfusion makes tumors hypoxic and induces the HIFs, which promote cell survival. We previously showed that hypoxic breast cancer cells are tamoxifen-resistant, and that HIF-inhibition restored tamoxifen-sensitivity. We found that HIF-induced tamoxifen-resistance involve cross-talk with epithelial growth factor receptor (EGFR), which itself is linked to tamoxifen resistance. Contralateral breast cancer (CBC), i.e. development of a second breast cancer in the contralateral breast despite adjuvant tamoxifen treatment is in essence a human in vivo-model for tamoxifen-resistance that we explore here to find molecular pathways of tamoxifen-resistance.
methodsWe constructed a tissue-microarray including tumor-tissue from a large well-defined cohort of CBC-patients, a proportion of which got their second breast cancer despite ongoing adjuvant therapy. Using immunohistochemistry >500 patients were evaluable for HIF-1α and EGFR in both tumors, and correlations to treatment, patient outcome, prognostic and predictive factors were analyzed.
resultsWe found an increased proportion of HIF-1α-positive tumors in tamoxifen-resistant (CBC during adjuvant tamoxifen) compared to naïve tumors (CBC without prior tamoxifen). Tumor HIF-1α-positivity correlated to increased breast cancer mortality, and negative prognostic factors including low age at diagnosis and ER-negativity. There was a covariance of HIF-1α- and EGFR-expression and also EGFR-expression correlated to poor prognosis.
conclusionsThe increased percentage of HIF-1α-positive tumors formed during adjuvant tamoxifen suggests a role for HIF-1α in escaping tamoxifen's restraining effects on breast cancer. Implicating a potential benefit of HIF-inhibitors in targeting breast cancers resistant to endocrine therapy.
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