Assessment of ESR1, PGR, ERBB2, and MKI67 mRNA in Hormone Receptor‐Positive Early Breast Cancer: A Cross‐Sectional Study

TL;DR

This study compares mRNA and IHC methods for assessing hormone receptor markers in early breast cancer, finding high concordance and suggesting mRNA tests could improve standardization.

Contribution

The study introduces mRNA-based testing as a more reliable alternative to IHC for hormone receptor assessment in breast cancer.

Findings

High concordance (95.9%) between ESR1 mRNA and ER IHC results was observed.

ERBB2/HER2 showed 100% concordance between mRNA and IHC methods.

ESR1 expression was significantly lower in tumors from younger patients.

Abstract

Hormone receptors are expressed in 70% of breast cancers and are the major biomarkers for tailoring treatment in early‐stage breast cancer. In clinical routine, immunohistochemistry (IHC) is used to assess estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 protein expression. However, IHC procedure is challenged with pre‐analytical and analytical variability. Pathologist interpretation of IHC results can vary, and discordant results between local and reference laboratories have been reported. Using mRNA‐based tests may be a more robust, reliable, and standardized method to assess these important breast cancer biomarkers. This study aimed to assess the concordance between real‐time PCR and IHC results.

In this study, we analyzed 178 early‐stage hormone receptor‐positive breast tumors. IHC for ER, PR, HER2, and Ki67 had been previously performed for the study samples at local laboratories. For samples with HER2 IHC score 2+, Fluorescence In Situ Hybridization was performed. ESR1 (encoding ER), PGR (encoding PR), ERBB2 (encoding HER2), and MKI67 (encoding Ki67) mRNA expression were determined using TaqMan gene expression assays.

The overall concordance between mRNA expression results and their corresponding IHC markers was 95.9% for ESR1/ER, 79.3% for PGR/PR, and 100% for ERBB2/HER2. There was a moderate correlation between MKi67 mRNA values and Ki67 IHC. ESR1 expression was significantly lower in tumors of younger patients (p < 0.001). No statistically significant correlation between age at cancer diagnosis and ER IHC was identified. Higher ESR1 and MKI67 mRNA expression was associated with worse pathological characteristics.

PCR‐based classification of breast tumors in a central laboratory may be used to confirm the available IHC results performed at local laboratories and add valuable information for patient management. mRNA‐based biomarkers may be promising for more standardized breast cancer management.

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