# Outcome prediction of oestrogen receptor‐positive breast cancer based on a panel of oestrogen receptor‐regulated genes

## TL;DR

This study identifies PR and GREB1 as key genes that can predict response to endocrine therapy in estrogen receptor-positive breast cancer patients.

## Contribution

The study identifies PR and GREB1 as independent prognostic biomarkers for endocrine therapy response in ER+ breast cancer.

## Key findings

- PR and GREB1 are independent predictors of endocrine therapy response in ER+ breast cancer.
- Combined PR-GREB1 expression is a strong predictor of endocrine therapy response.
- Only four genes (PR, GREB1, AR, BEX1) showed prognostic significance at both transcriptomic and proteomic levels.

## Abstract

The response of oestrogen receptor‐positive (ER+) breast cancers (BC) to endocrine therapy (ET) is variable. ER pathway‐regulated genes have been proposed to play a role in response to ET. In this study, we investigated the prognostic and predictive impacts of the expression of key ER‐regulated genes in BC.

The Cancer Genome Atlas data was used to identify differentially expressed genes (DEG) associated with ER‐positivity. Of the DEGs (1329 upregulated and 1188 downregulated genes), 21 top genes showed biological and clinical relevance to ER functions and were further investigated. Publicly available transcriptomic datasets were utilised to evaluate the clinical significance of the expression of these 21 genes. The well‐characterised Nottingham operable BC cohort was used to assess their protein expression. Genes that demonstrated prognostic significance on both levels were subsequently tested individually and in combination using multivariate Cox regression analysis.

Of the 21 assessed ER‐regulated genes, four genes (PR, GREB1, AR and BEX1) maintained their prognostic significance in ER+ BC at both the transcriptomic and proteomic levels. Multivariate Cox regression analyses showed that only PR and GREB1 are predictors of ET response independent of tumour grade, size or lymph node status. The combined PR‐GREB1 expression was a strong predictor of ET response.

This study showed that when several ER‐related biomarkers were evaluated, only PR and GREB1 retained their independent prognostic significance and can be used, individually or in combination, to predict the response to ET in ER+ BC patients.

A flow chart of oestrogen receptor‐regulated genes of predictive value in breast cancer.