ArticleEBioMedicine2015
Osteoprotegerin (OPG), The Endogenous Inhibitor of Receptor Activator of NF-κB Ligand (RANKL), is Dysregulated in BRCA Mutation Carriers.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 69 citations in OpenAlex.
- Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women.Genome medicine · 2022Trial
- Activation of RANK/RANKL/OPG Pathway Is Involved in the Pathophysiology of Fibrous Dysplasia and Associated With Disease Burden.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Trial
- Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.World journal of experimental medicine · 2026Review
- Individualised progesterone receptor modulator prevention strategies for triple-negative breast cancer in BRCA1 pathogenic variant carriers.NPJ breast cancer · 2026Review
- The landscape of malignant transition: Unraveling cancer cell-of-origin and heterogeneous tissue microenvironment.Cancer letters · 2025Article
- Epigenetic signatures in surrogate tissues are able to assess cancer risk and indicate the efficacy of preventive measures.Communications medicine · 2025Article
- Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies.International journal of molecular sciences · 2025Review
- Delineating the relationship between circulating osteoprotegerin and bone health in women with a pathogenic variant inBone reports · 2024Article
- Correlation of RANK and RANKL with mammographic density in primary breast cancer patients.Archives of gynecology and obstetrics · 2024Article
- Single-cell Landscape of Malignant Transition: Unraveling Cancer Cell-of-Origin and Heterogeneous Tissue Microenvironment.Research square · 2024Article
- Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.Breast cancer research and treatment · 2023Article
- Beyond the pill: contraception and the prevention of hereditary ovarian cancer.Hereditary cancer in clinical practice · 2022Review
- A human breast atlas integrating single-cell proteomics and transcriptomics.Developmental cell · 2022Article
- The roles of osteoprotegerin in cancer, far beyond a bone player.Cell death discovery · 2022Review
- Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation.Hereditary cancer in clinical practice · 2022Review
- Management Strategies of Breast Cancer Patients withOncoTargets and therapy · 2022Review
- Physical activity and Mediterranean diet as potential modulators of osteoprotegerin and soluble RANKL in gBRCA1/2 mutation carriers: results of the lifestyle intervention pilot study LIBRE-1.Breast cancer research and treatment · 2021Article
- New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.Molecules (Basel, Switzerland) · 2021Review
- The Roadmap of RANKL/RANK Pathway in Cancer.Cells · 2021Review
- Plasma Protein Biomarkers Associated with Higher Ovarian Cancer Risk in BRCA1/2 Carriers.Cancers · 2021Article
Corrections and comments
- Commented on by
Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Breast cancer development in BRCA1/2 mutation carriers is a net consequence of cell-autonomous and cell nonautonomous factors which may serve as excellent targets for cancer prevention. In light of our previous data we sought to investigate the consequences of the BRCA-mutation carrier state on RANKL/osteoprotegerin (OPG) signalling. We analysed serum levels of RANKL, OPG, RANKL/OPG complex, oestradiol (E2), and progesterone (P) during menstrual cycle progression in 391 BRCA1/2-mutation carriers and 782 noncarriers. These studies were complemented by analyses of RANKL and OPG in the serum and mammary tissues of female cynomolgus macaques (n = 88) and serum RANKL and OPG in postmenopausal women (n = 150). BRCA-mutation carriers had lower mean values of free serum OPG in particular in BRCA1-mutation carriers (p = 0.018) compared with controls. Among BRCA1/2 mutation carriers, lower OPG levels were associated with germline mutation locations known to confer an increased breast cancer risk (p = 0.003). P is associated with low OPG levels in serum and tissue, particularly in BRCA-mutation carriers (rho = - 0.216; p = 0.002). Serum OPG levels were inversely correlated (rho = - 0.545, p < 0.001) with mammary epithelial proliferation measured by Ki67 expression and increased (p = 0.01) in postmenopause. The P-RANKL/OPG system is dysregulated in BRCA-mutation carriers. These and previously published data provide a strong rationale for further investigation of antiprogestogens or an anti-RANKL antibody such as denosumab for breast cancer prevention.
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.