ArticleJournal of the National Cancer Institute2017
Effects of In Utero Exposure to Ethinyl Estradiol on Tamoxifen Resistance and Breast Cancer Recurrence in a Preclinical Model.
Article in Journal of the National Cancer Institute, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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
21 citing papers in PubMed, 34 citations in OpenAlex.
- Behavior of Osteoblastic Lineage Cells When in the Presence of Tamoxifen: In Vitro and In Vivo Studies on Osseointegration.Dentistry journal · 2025Article
- Association of Galectin-3 but not Laminin in Tamoxifen-Induced Growth Suppression in Breast Cancer MCF-7 Cells.International journal of biochemistry & physiology · 2025Article
- A Review on Cyclodextrins/Estrogens Inclusion Complexes.International journal of molecular sciences · 2023Review
- Article
- Stilbenes: a promising small molecule modulator for epigenetic regulation in human diseases.Frontiers in pharmacology · 2023Review
- Somatic point mutations are enriched in non-coding RNAs with possible regulatory function in breast cancer.Communications biology · 2022Article
- Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes.International journal of environmental research and public health · 2022Review
- E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms.Molecular therapy oncolytics · 2021Review
- Experimental models of endocrine responsive breast cancer: strengths, limitations, and use.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- 3,3'-Diindolylmethane Enhances Paclitaxel Sensitivity by Suppressing DNMT1-Mediated KLF4 Methylation in Breast Cancer.Frontiers in oncology · 2021Article
- Maternal obesity increases offspring's mammary cancer recurrence and impairs tumor immune response.Endocrine-related cancer · 2020Article
- Reversal of increased mammary tumorigenesis by valproic acid and hydralazine in offspring of dams fed high fat diet during pregnancy.Scientific reports · 2019Article
- Endoplasmic Reticulum Stress Pathway, the Unfolded Protein Response, Modulates Immune Function in the Tumor Microenvironment to Impact Tumor Progression and Therapeutic Response.International journal of molecular sciences · 2019Review
- Increased expression of the HDAC9 gene is associated with antiestrogen resistance of breast cancers.Molecular oncology · 2019Article
- Systems biology: perspectives on multiscale modeling in research on endocrine-related cancers.Endocrine-related cancer · 2019Review
- Increased LGALS3 expression independently predicts shorter overall survival in patients with the proneural subtype of glioblastoma.Cancer medicine · 2019Article
- Effects of Jaeumkanghwa-tang on tamoxifen responsiveness in preclinical ER+ breast cancer model.Endocrine-related cancer · 2019Article
- EGR1 regulates cellular metabolism and survival in endocrine resistant breast cancer.Oncotarget · 2017Article
- Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.Breast cancer research : BCR · 2017Article
- Association of Smoking, Alcohol Use, and Betel Quid Chewing with Epigenetic Aberrations in Cancers.International journal of molecular sciences · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Background: Responses to endocrine therapies vary among patients with estrogen receptor (ER+) breast cancer. We studied whether in utero exposure to endocrine-disrupting compounds might explain these variations. Methods: We describe a novel ER+ breast cancer model to study de novo and acquired tamoxifen (TAM) resistance. Pregnant Sprague Dawley rats were exposed to 0 or 0.1 ppm ethinyl estradiol (EE2), and the response of 9,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors to 15 mg/kg TAM, with (n = 17 tumors in the controls and n = 20 tumors in EE2 offspring) or without 1.2 g/kg valproic acid and 5 mg/kg hydralazine (n = 24 tumors in the controls and n = 32 tumors in EE2 offspring) in the female offspring, was assessed. One-sided Chi2 tests were used to calculate P values. Comparisons of differentially expressed genes between mammary tumors in in utero EE2-exposed and control rats, and between anti-estrogen-resistant LCC9 and -sensitive LCC1 human breast cancer cells, were also performed. Results: In our preclinical model, 54.2% of mammary tumors in the control rats exhibited a complete response to TAM, of which 23.1% acquired resistance with continued anti-estrogen treatment and recurred. Mammary tumors in the EE2 offspring were statistically significantly less likely to respond to TAM (P = .047) and recur (P = .007). In the EE2 offspring, but not in controls, adding valproic acid and hydralazine to TAM prevented recurrence (P < .001). Three downregulated and hypermethylated genes (KLF4, LGALS3, MICB) and one upregulated gene (ETV4) were identified in EE2 tumors and LCC9 breast cancer cells, and valproic acid and hydralazine normalized the altered expression of all four genes. Conclusions: Resistance to TAM may be preprogrammed by in utero exposure to high estrogen levels and mediated through reversible epigenetic alterations in genes associated with epithelial-mesenchymal transition and tumor immune responses.
Indexed as
Identifiers
What OpenQuestion holds
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.