Hormone receptor mRNA and protein levels as predictors of premenopausal tamoxifen benefit

Authors

DOI:

https://doi.org/10.2340/1651-226X.2024.19655

Keywords:

breast cancer, tamoxifen, premenopausal patients, randomized trial, estrogen receptor status, progesterone receptor status, predictive information

Abstract

ABSTRACT

Background and purpose: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen.

Patients and Methods: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years.

Results: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36–0.79]; IHC-ER+ 0.55 [0.38–0.79]; GEX-ER+ 0.54 [0.37–0.77]; cytosol-PR+ 0.49 [0.34–0.72]; IHC-PR+ 0.58 [0.40–0.85]; GEX-PR+ 0.55 [0.38–0.80]). Results were similar for OS.

Interpretation: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.

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Author Biographies

Terese Engström, Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden

First author

Julia Tutzauer, Department of Clinical Sciences Lund, Division of Oncology, Lund University, Lund, Sweden

Corresponding author

Co-last author

Lisa Rydén, Department of Clinical Sciences Lund, Division of Surgery and Oncology, Lund University, Lund, Sweden; Department of Surgery, Skåne University Hospital, Malmö, Sweden

Co-last author

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2024-04-08

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Engström, T., Ekholm, M., Fernö, M., Lundgren, C., Nordenskjöld, B., Stål, O., Bendahl, P.-O., Tutzauer, J., & Rydén, L. (2024). Hormone receptor mRNA and protein levels as predictors of premenopausal tamoxifen benefit. Acta Oncologica, 63(1), 125–136. https://doi.org/10.2340/1651-226X.2024.19655

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Vol. 63 (2024): Acta Oncologica

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Copyright (c) 2024 Terese Engström, Maria Ekholm, Mårten Fernö, Christine Lundgren, Bo Nordenskjöld, Olle Stål, Pär-Ola Bendahl, Julia Tutzauer, Lisa Rydén

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