ArticleBreast cancer research : BCR2013
Progestin effects on cell proliferation pathways in the postmenopausal mammary gland.
Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- OPG and PgR show similar cohort specific effects as prognostic factors in ER positive breast cancer.Molecular oncology · 2014Pooled it
- Effects of Estradiol/Micronized Progesterone vs. Conjugated Equine Estrogens/Medroxyprogesterone Acetate on Breast Cancer Gene Expression in Healthy Postmenopausal Women.International journal of molecular sciences · 2023Trial
- Correlation of RANK and RANKL with mammographic density in primary breast cancer patients.Archives of gynecology and obstetrics · 2024Article
- Mechanosensitive hormone signaling promotes mammary progenitor expansion and breast cancer risk.Cell stem cell · 2024Article
- RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer.Geburtshilfe und Frauenheilkunde · 2024Article
- Phosphotungstic acid-enhanced microcomputed tomography for quantitative visualization of mouse mammary gland morphology.Journal of medical imaging (Bellingham, Wash.) · 2023Article
- Multivariate analysis of independent roles of socioeconomic status, occupational physical activity, reproductive factors, and postmenopausal hormonal therapy in risk of breast cancer.Breast cancer research and treatment · 2022Article
- RANKL/RANK promotes the migration of gastric cancer cells by interacting with EGFR.Clinical and translational medicine · 2020Article
- RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives.Journal of experimental & clinical cancer research : CR · 2019Review
- The Proliferative Response to p27 Down-Regulation in Estrogen Plus Progestin Hormonal Therapy is Lost in Breast Tumors.Translational oncology · 2018Article
- Osteoprotegerin and breast cancer risk by hormone receptor subtype: a nested case-control study in the EPIC cohort.BMC medicine · 2017Article
- RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.Nature medicine · 2016Article
- Osteoprotegerin (OPG), The Endogenous Inhibitor of Receptor Activator of NF-κB Ligand (RANKL), is Dysregulated in BRCA Mutation Carriers.EBioMedicine · 2015Article
- Hormone-sensing mammary epithelial progenitors: emerging identity and hormonal regulation.Journal of mammary gland biology and neoplasia · 2015Review
- Steroid hormones, steroid receptors, and breast cancer stem cells.Journal of mammary gland biology and neoplasia · 2015Review
- RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy.Breast cancer research : BCR · 2015Article
- Hormonal regulation of the immune microenvironment in the mammary gland.Journal of mammary gland biology and neoplasia · 2014Review
- Tracking progesterone receptor-mediated actions in breast cancer.Pharmacology & therapeutics · 2014Review
- Mammary stem cells: expansion and animal productivity.Journal of animal science and biotechnology · 2014Review
- Targeting RANKL in metastasis.BoneKEy reports · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
introductionMenopausal hormone therapies vary widely in their effects on breast cancer risk, and the mechanisms underlying these differences are unclear. The primary goals of this study were to characterize the mammary gland transcriptional profile of estrogen + progestin therapy in comparison with estrogen-alone or tibolone and investigate pathways of cell proliferation in a postmenopausal primate model.
methodsOvariectomized female cynomolgus macaque monkeys were randomized into the following groups: placebo (Con), oral conjugated equine estrogens (CEE), CEE with medroxyprogesterone acetate (MPA) (CEE + MPA), and tibolone given at a low or high dose (Lo or Hi Tib). All study treatment doses represented human clinical dose equivalents and were administered in the diet over a period of 2 years.
resultsTreatment with CEE + MPA had the greatest effect on global mRNA profiles and markers of mammary gland proliferation compared to CEE or tibolone treatment. Changes in the transcriptional patterns resulting from the addition of MPA to CEE were related to increased growth factors and decreased estrogen receptor (ER) signaling. Specific genes induced by CEE + MPA treatment included key members of prolactin receptor (PRLR)/signal transducer and activator of transcription 5 (STAT5), epidermal growth factor receptor (EGFR), and receptor activator of nuclear factor kappa B (RANK)/receptor activator of nuclear factor kappa B ligand (RANKL) pathways that were highly associated with breast tissue proliferation. In contrast, tibolone did not affect breast tissue proliferation but did elicit a mixed pattern of ER agonist activity.
conclusionOur findings indicate that estrogen + progestin therapy results in a distinct molecular profile compared to estrogen-alone or tibolone therapy, including upregulation of key growth factor targets associated with mammary carcinogenesis in mouse models. These changes may contribute to the promotional effects of estrogen + progestin therapy on breast cancer risk.
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