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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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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. |
format | Online Article Text |
id | pubmed-6265321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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