ArticleJournal of the National Cancer Institute2017
Progesterone Receptor Isoform Ratio: A Breast Cancer Prognostic and Predictive Factor for Antiprogestin Responsiveness.
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 38 papers, 2 of them syntheses that pooled it.
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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
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.
- Progesterone Receptor Gene Polymorphisms and Breast Cancer Risk.Endocrinology · 2023Pooled it
- Relevance of humanized three-dimensional tumor tissue models: a descriptive systematic literature review.Cellular and molecular life sciences : CMLS · 2020Pooled it
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- A proteogenomic RNA processing mechanism drives sex differences in meningioma.Research square · 2026Article
- Nuclear FGF2, androgen receptor and Wnt pathway activation define a targetable subset of antiprogestin-resistant luminal breast cancer.British journal of cancer · 2026Article
- Functional roles of Keratin 6A in disease pathogenesis across cancer and skin disorders.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Endocrine Examples of Phase Separation in Biology.Endocrinology · 2025Review
- Progesterone Receptor Signaling Promotes Cancer Associated Fibroblast Mediated Tumorigenicity in ER+ Breast Cancer.Endocrinology · 2024Article
- How Progesterone Receptor Expression Impacts Platinum Sensitivity in Ovarian Clear Cell Carcinoma: Insights from Clinical and Experimental Perspectives.International journal of molecular sciences · 2024Article
- Steroid profile in patients with breast cancer and in mice treated with mifepristone.Endocrine-related cancer · 2024Article
- Reevaluating the Role of Progesterone in Ovarian Cancer: Is Progesterone Always Protective?Endocrine reviews · 2023Article
- Beneficial Effects of Mifepristone Treatment in Patients with Breast Cancer Selected by the Progesterone Receptor Isoform Ratio: Results from the MIPRA Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Editorial: Steroid hormone receptors and cell cycle in breast cancer.Frontiers in endocrinology · 2023Article
- Progestogens exhibit progestogen-, promoter- and isoform-specific effects via the progesterone receptor.Steroids · 2022Article
- Novel insights linking BRCA1-IRIS role in mammary gland development to formation of aggressive PABCs: the case for longer breastfeeding.American journal of cancer research · 2022Article
- Choosing the right partner in hormone-dependent gene regulation: Glucocorticoid and progesterone receptors crosstalk in breast cancer cells.Frontiers in endocrinology · 2022Review
- The Role of Progesterone Receptors in Breast Cancer.Drug design, development and therapy · 2022Review
- Article
- Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.Cancers · 2021Review
- Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Background: Compelling evidence shows that progestins regulate breast cancer growth. Using preclinical models, we demonstrated that antiprogestins are inhibitory when the level of progesterone receptor isoform A (PR-A) is higher than that of isoform B (PR-B) and that they might stimulate growth when PR-B is predominant. The aims of this study were to investigate ex vivo responses to mifepristone (MFP) in breast carcinomas with different PR isoform ratios and to examine their clinical and molecular characteristics. Methods: We performed human breast cancer tissue culture assays (n = 36) to evaluate the effect of MFP on cell proliferation. PR isoform expression was determined by immunoblotting (n = 282). Tumors were categorized as PRA-H (PR-A/PR-B ≥ 1.2) or PRB-H (PR-A/PR-B ≤ 0.83). RNA was extracted for Ribo-Zero-Seq sequencing to evaluate differentially expressed genes. Subtypes and risk scores were predicted using the PAM50 gene set, the data analyzed using The Cancer Genome Atlas RNA-seq gene analysis and other publicly available gene expression data. Tissue microarrays were performed using paraffin-embedded tissues (PRA-H n = 53, PRB-H n = 24), and protein expression analyzed by immunohistochemistry. All statistical tests were two-sided. Results: One hundred sixteen out of 222 (52.3%) PR+ tumors were PRA-H, and 64 (28.8%) PRB-H. Cell proliferation was inhibited by MFP in 19 of 19 tissue cultures from PRA-H tumors. A total of 139 transcripts related to proliferative pathways were differentially expressed in nine PRA-H and seven PRB-H tumors. PRB-H and PRA-H tumors were either luminal B or A phenotypes, respectively ( P = .03). PRB-H cases were associated with shorter relapse-free survival (hazard ratio [HR] = 2.70, 95% confidence interval [CI] = 1.71 to 6.20, P = .02) and distant metastasis-free survival (HR = 4.17, 95% CI = 2.18 to 7.97, P < .001). PRB-H tumors showed increased tumor size ( P < .001), Ki-67 levels ( P < .001), human epidermal growth factor receptor 2 expression ( P = .04), high grades ( P = .03), and decreased total PR ( P = .004) compared with PRA-H tumors. MUC-2 ( P < .001) and KRT6A ( P = .02) were also overexpressed in PRB-H tumors. Conclusion: The PRA/PRB ratio is a prognostic and predictive factor for antiprogestin responsiveness in 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.