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

Engström, Terese ; Ekholm, Maria ; Fernö, Mårten LU ; Lundgren, Christine LU ; Nordenskjöld, Bo ; Stål, Olle ; Bendahl, Pär Ola LU ; Tutzauer, Julia LU orcid and Rydén, Lisa LU orcid (2024) In Acta Oncologica 63. p.125-136
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,... (More)

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
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
breast cancer, estrogen receptor status, predictive information, premenopausal patients, progesterone receptor status, randomized trial, tamoxifen
in
Acta Oncologica
volume
63
pages
12 pages
publisher
Taylor & Francis
external identifiers
  • pmid:38587062
  • scopus:85190398028
ISSN
0284-186X
DOI
10.2340/1651-226X.2024.19655
language
English
LU publication?
yes
id
28be4a57-8761-441a-ae03-0f019152065c
date added to LUP
2024-05-20 13:55:03
date last changed
2024-07-15 19:28:11
@article{28be4a57-8761-441a-ae03-0f019152065c,
  abstract     = {{<p>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.</p>}},
  author       = {{Engström, Terese and Ekholm, Maria and Fernö, Mårten and Lundgren, Christine and Nordenskjöld, Bo and Stål, Olle and Bendahl, Pär Ola and Tutzauer, Julia and Rydén, Lisa}},
  issn         = {{0284-186X}},
  keywords     = {{breast cancer; estrogen receptor status; predictive information; premenopausal patients; progesterone receptor status; randomized trial; tamoxifen}},
  language     = {{eng}},
  pages        = {{125--136}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta Oncologica}},
  title        = {{Hormone receptor mRNA and protein levels as predictors of premenopausal tamoxifen benefit}},
  url          = {{http://dx.doi.org/10.2340/1651-226X.2024.19655}},
  doi          = {{10.2340/1651-226X.2024.19655}},
  volume       = {{63}},
  year         = {{2024}},
}