Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance

Makhlouf, Shorouk; Quinn, Cecily; Toss, Michael; Alsaleem, Mansour; Atallah, Nehal M; Ibrahim, Asmaa; Rutland, Catrin S; Mongan, Nigel P; Rakha, Emad A

Abstract

Background

Oestrogen receptor (ER) positive breast cancer (BC) patients are eligible for endocrine therapy (ET), regardless of ER immunohistochemical expression level. There is a wide spectrum of ER expression and the response to ET is not uniform. This study aimed to assess the clinical and molecular consequences of ER heterogeneity with respect to ET-response.

Methods

ER expression, categorised by percentage and staining intensity in a large BC cohort (n = 7559) was correlated with clinicopathological parameters and patient ET response. The Cancer Genome Atlas Data BC cohort (n = 1047) was stratified by ER expression and transcriptomic analysis completed to better understand the molecular basis of ER heterogeneity.

Results

The quantitative proportional increase in ER expression was positively associated with favourable prognostic parameters. Tumours with 1–9% ER expression were characteristically similar to ER-negative (<1%) tumours. Maximum ET-response was observed in tumours with 100% ER expression, with responses significantly different to tumours exhibiting ER at < 100% and significantly decreased survival rates were observed in tumours with 50% and 10% of ER expression. The Histochemical-score (H-score), which considers both staining intensity and percentage, added significant prognostic value over ER percentage alone with significant outcome differences observed at H-scores of 30, 100 and 200. There was a positive correlation between ER expression and ESR1 mRNA expression and expression of ER-regulated genes. Pathway analysis identified differential expression in key cancer-related pathways in different ER-positive groups.

Conclusion

ET-response is statistically proportionally related to ER expression with significant differences observed at 10%, 50% and 100%. The H-score adds prognostic and predictive information.

Citation

Makhlouf, S., Quinn, C., Toss, M., Alsaleem, M., Atallah, N. M., Ibrahim, A., Rutland, C. S., Mongan, N. P., & Rakha, E. A. (2024). Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance. European Journal of Cancer, 197, Article 113473. https://doi.org/10.1016/j.ejca.2023.113473

• Journal Article Type: Article
• Acceptance Date: Dec 4, 2023
• Online Publication Date: Dec 11, 2023
• Publication Date: Jan 1, 2024
• Deposit Date: Dec 19, 2023
• Publicly Available Date: Dec 20, 2023
• Journal: European Journal of Cancer
• Print ISSN: 0959-8049
• Electronic ISSN: 1879-0852
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 197
• Article Number: 113473
• DOI: https://doi.org/10.1016/j.ejca.2023.113473
• Keywords: Oestrogen receptor, Endocrine therapy, Breast cancer, Heterogenous expression
• Public URL: https://nottingham-repository.worktribe.com/output/28708615
• Publisher URL: https://doi.org/10.1016/j.ejca.2023.113473
• PMID: 38103327
• Additional Information: This article is maintained by: Elsevier; Article Title: Quantitative expression of oestrogen receptor in breast cancer: Clinical and molecular significance; Journal Title: European Journal of Cancer; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ejca.2023.113473; Content Type: article; Copyright: © 2023 The Author(s). Published by Elsevier Ltd.