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Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b

BACKGROUND: Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-α (ER) and reprogrammes transcription toward better breast cancer outcomes. We investigated whether ER and PR-B interactions were present in breast t...

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Autores principales: Snell, Cameron E., Gough, Madeline, Liu, Cheng, Middleton, Kathryn, Pyke, Christopher, Shannon, Catherine, Woodward, Natasha, Hickey, Theresa E., Armes, Jane E., Tilley, Wayne D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265321/
https://www.ncbi.nlm.nih.gov/pubmed/30410061
http://dx.doi.org/10.1038/s41416-018-0331-3
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author Snell, Cameron E.
Gough, Madeline
Liu, Cheng
Middleton, Kathryn
Pyke, Christopher
Shannon, Catherine
Woodward, Natasha
Hickey, Theresa E.
Armes, Jane E.
Tilley, Wayne D.
author_facet Snell, Cameron E.
Gough, Madeline
Liu, Cheng
Middleton, Kathryn
Pyke, Christopher
Shannon, Catherine
Woodward, Natasha
Hickey, Theresa E.
Armes, Jane E.
Tilley, Wayne D.
author_sort Snell, Cameron E.
collection PubMed
description BACKGROUND: Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-α (ER) and reprogrammes transcription toward better breast cancer outcomes. We investigated whether ER and PR-B interactions were present in breast tumours and associated with clinical parameters including response to aromatase inhibitors. METHODS: We developed a proximity ligation assay to detect ER and PR-B (ER:PR-B) interactions in formalin-fixed paraffin-embedded tissues. The assay was validated in a cell line and patient-derived breast cancer explants and applied to a cohort of 229 patients with ER-positive and HER2-negative breast cancer with axillary nodal disease. RESULTS: Higher frequency of ER:PR-B interaction correlated with increasing patient age, lower tumour grade and mitotic index. A low frequency of ER:PR-B interaction was associated with higher risk of relapse. In multivariate analysis, ER:PR-B interaction frequency was an independent predictive factor for relapse, whereas PR expression was not. In subset analysis, low frequency of ER:PR-B interaction was predictive of relapse on adjuvant aromatase inhibitor (HR 4.831, p = 0.001), but not on tamoxifen (HR 1.043, p = 0.939). CONCLUSIONS: This study demonstrates that ER:PR-B interactions have utility in predicting patient response to adjuvant AI therapy.
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spelling pubmed-62653212019-11-09 Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b Snell, Cameron E. Gough, Madeline Liu, Cheng Middleton, Kathryn Pyke, Christopher Shannon, Catherine Woodward, Natasha Hickey, Theresa E. Armes, Jane E. Tilley, Wayne D. Br J Cancer Article BACKGROUND: Recent pre-clinical studies indicate that activated progesterone receptor (PR) (particularly the PR-B isoform) binds to oestrogen receptor-α (ER) and reprogrammes transcription toward better breast cancer outcomes. We investigated whether ER and PR-B interactions were present in breast tumours and associated with clinical parameters including response to aromatase inhibitors. METHODS: We developed a proximity ligation assay to detect ER and PR-B (ER:PR-B) interactions in formalin-fixed paraffin-embedded tissues. The assay was validated in a cell line and patient-derived breast cancer explants and applied to a cohort of 229 patients with ER-positive and HER2-negative breast cancer with axillary nodal disease. RESULTS: Higher frequency of ER:PR-B interaction correlated with increasing patient age, lower tumour grade and mitotic index. A low frequency of ER:PR-B interaction was associated with higher risk of relapse. In multivariate analysis, ER:PR-B interaction frequency was an independent predictive factor for relapse, whereas PR expression was not. In subset analysis, low frequency of ER:PR-B interaction was predictive of relapse on adjuvant aromatase inhibitor (HR 4.831, p = 0.001), but not on tamoxifen (HR 1.043, p = 0.939). CONCLUSIONS: This study demonstrates that ER:PR-B interactions have utility in predicting patient response to adjuvant AI therapy. Nature Publishing Group UK 2018-11-09 2018-11-27 /pmc/articles/PMC6265321/ /pubmed/30410061 http://dx.doi.org/10.1038/s41416-018-0331-3 Text en © Cancer Research UK 2018 https://creativecommons.org/licenses/by/4.0/This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Snell, Cameron E.
Gough, Madeline
Liu, Cheng
Middleton, Kathryn
Pyke, Christopher
Shannon, Catherine
Woodward, Natasha
Hickey, Theresa E.
Armes, Jane E.
Tilley, Wayne D.
Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
title Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
title_full Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
title_fullStr Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
title_full_unstemmed Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
title_short Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
title_sort improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265321/
https://www.ncbi.nlm.nih.gov/pubmed/30410061
http://dx.doi.org/10.1038/s41416-018-0331-3
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