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Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation

Women with a pathogenic germline mutation in the BRCA1 gene face a very high lifetime risk of developing breast cancer, estimated at 72% by age 80. Prophylactic bilateral mastectomy is the only effective way to lower their risk; however, most women with a mutation opt for intensive screening with an...

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Autores principales: Park, Sarah Sohyun, Uzelac, Aleksandra, Kotsopoulos, Joanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008947/
https://www.ncbi.nlm.nih.gov/pubmed/35418083
http://dx.doi.org/10.1186/s13053-022-00223-3
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author Park, Sarah Sohyun
Uzelac, Aleksandra
Kotsopoulos, Joanne
author_facet Park, Sarah Sohyun
Uzelac, Aleksandra
Kotsopoulos, Joanne
author_sort Park, Sarah Sohyun
collection PubMed
description Women with a pathogenic germline mutation in the BRCA1 gene face a very high lifetime risk of developing breast cancer, estimated at 72% by age 80. Prophylactic bilateral mastectomy is the only effective way to lower their risk; however, most women with a mutation opt for intensive screening with annual MRI and mammography. Given that the BRCA1 gene was identified over 20 years ago, there is a need to identify a novel non-surgical approach to hereditary breast cancer prevention. Here, we provide a review of the emerging preclinical and epidemiologic evidence implicating the dysregulation of progesterone-mediated receptor activator of nuclear factor κB (RANK) signaling in the pathogenesis of BRCA1-associated breast cancer. Experimental studies have demonstrated that RANK inhibition suppresses Brca1-mammary tumorigenesis, suggesting a potential target for prevention. Data from studies conducted among women with a BRCA1 mutation further support this pathway in BRCA1-associated breast cancer development. Progesterone-containing (but not estrogen-alone) hormone replacement therapy is associated with an increased risk of breast cancer in women with a BRCA1 mutation. Furthermore, BRCA1 mutation carriers have significantly lower levels of circulating osteoprotegerin (OPG), the decoy receptor for RANK-ligand (RANKL) and thus endogenous inhibitor of RANK signaling. OPG levels may be associated with the risk of disease, suggesting a role of this protein as a potential biomarker of breast cancer risk. This may improve upon current risk prediction models, stratifying women at the highest risk of developing the disease, and further identify those who may be targets for anti-RANKL chemoprevention. Collectively, the evidence supports therapeutic inhibition of the RANK pathway for the primary prevention of BRCA1-associated breast cancer, which may generate unique prevention strategies (without prophylactic surgery) and enhance quality of life.
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spelling pubmed-90089472022-04-15 Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation Park, Sarah Sohyun Uzelac, Aleksandra Kotsopoulos, Joanne Hered Cancer Clin Pract Review Women with a pathogenic germline mutation in the BRCA1 gene face a very high lifetime risk of developing breast cancer, estimated at 72% by age 80. Prophylactic bilateral mastectomy is the only effective way to lower their risk; however, most women with a mutation opt for intensive screening with annual MRI and mammography. Given that the BRCA1 gene was identified over 20 years ago, there is a need to identify a novel non-surgical approach to hereditary breast cancer prevention. Here, we provide a review of the emerging preclinical and epidemiologic evidence implicating the dysregulation of progesterone-mediated receptor activator of nuclear factor κB (RANK) signaling in the pathogenesis of BRCA1-associated breast cancer. Experimental studies have demonstrated that RANK inhibition suppresses Brca1-mammary tumorigenesis, suggesting a potential target for prevention. Data from studies conducted among women with a BRCA1 mutation further support this pathway in BRCA1-associated breast cancer development. Progesterone-containing (but not estrogen-alone) hormone replacement therapy is associated with an increased risk of breast cancer in women with a BRCA1 mutation. Furthermore, BRCA1 mutation carriers have significantly lower levels of circulating osteoprotegerin (OPG), the decoy receptor for RANK-ligand (RANKL) and thus endogenous inhibitor of RANK signaling. OPG levels may be associated with the risk of disease, suggesting a role of this protein as a potential biomarker of breast cancer risk. This may improve upon current risk prediction models, stratifying women at the highest risk of developing the disease, and further identify those who may be targets for anti-RANKL chemoprevention. Collectively, the evidence supports therapeutic inhibition of the RANK pathway for the primary prevention of BRCA1-associated breast cancer, which may generate unique prevention strategies (without prophylactic surgery) and enhance quality of life. BioMed Central 2022-04-13 /pmc/articles/PMC9008947/ /pubmed/35418083 http://dx.doi.org/10.1186/s13053-022-00223-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Park, Sarah Sohyun
Uzelac, Aleksandra
Kotsopoulos, Joanne
Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation
title Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation
title_full Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation
title_fullStr Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation
title_full_unstemmed Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation
title_short Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation
title_sort delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a brca1 mutation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008947/
https://www.ncbi.nlm.nih.gov/pubmed/35418083
http://dx.doi.org/10.1186/s13053-022-00223-3
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