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https://hdl.handle.net/2440/117583
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Type: | Journal article |
Title: | Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-α and progesterone receptor-b |
Other Titles: | Improved relapse-free survival on aromatase inhibitors in breast cancer is associated with interaction between oestrogen receptor-alpha and progesterone receptor-b |
Author: | Snell, C. Gough, M. Liu, C. Middleton, K. Pyke, C. Shannon, C. Woodward, N. Hickey, T. Armes, J. Tilley, W. |
Citation: | British Journal of Cancer, 2018; 119(11):1316-1325 |
Publisher: | Springer Nature |
Issue Date: | 2018 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | Cameron E. Snell, Madeline Gough, Cheng Liu, Kathryn Middleton, Christopher Pyke, Catherine Shannon, Natasha Woodward, Theresa E. Hickey, Jane E. Armes and Wayne D. Tilley |
Abstract: | 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. |
Keywords: | Cell Line, Tumor Humans Breast Neoplasms Neoplasm Recurrence, Local Estrogen Receptor alpha Receptors, Progesterone Disease-Free Survival Immunohistochemistry Cohort Studies Adult Aged Middle Aged Female |
Rights: | © Cancer Research UK 2018 Note: 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). |
DOI: | 10.1038/s41416-018-0331-3 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1130077 |
Published version: | http://dx.doi.org/10.1038/s41416-018-0331-3 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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hdl_117583.pdf | Published version | 1.2 MB | Adobe PDF | View/Open |
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