Abstract
Triple negative breast cancer (TNBC) is a poor outcome subset of breast cancers characterised by the lack of expression of ER α, PR, and HER2 amplification. It is a heterogeneous group of cancers which fail to derive benefit from modern, more targeted treatments such as Tamoxifen and Herceptin. Current standard of care (SoC) is cytotoxic chemotherapy, which is effective for some patients, with other patients deriving little/no benefit and lacking alternative treatments. This study has identified the glucocorticoid receptor (GR) as a potential predictive biomarker of response to anthracycline-based chemotherapy in triple negative breast cancer (TNBC). GR gene expression levels in patient samples were analysed through publicly available microarray datasets as well as protein expression through immunohistochemistry (IHC) and correlated with clinical/pathological outcomes, including survival. While the results confirmed previous observations that high GR expression is associated with poor outcome in response to taxane-based chemotherapy, this study shows for the first time that high GR expression is associated with improved outcomes in the context of anthracycline-based chemotherapy. GR therefore has the potential to be used as a predictive biomarker to guide treatment choices and ensure that patients derive the greatest benefit from first line treatment, avoiding unnecessary costs, side effects, and disease progression.
Highlights
Breast cancer is the most common malignancy in females worldwide, with over 2 million new cases diagnosed in 2018 and an estimated 600,000 deaths [1]
We expanded the analysis to a cohort which consisted of 205 FEC treated patients spanning the molecular subgroups of breast cancer as defined by the St
To verify whether glucocorticoid receptor (GR) was prognostic of Triple negative breast cancer (TNBC) pathology and disease progression or whether it was a predictive marker of response to chemotherapy, we identified an untreated cohort of ER negative patients from the TRANSBIG study (GSE7390) [20]
Summary
Breast cancer is the most common malignancy in females worldwide, with over 2 million new cases diagnosed in 2018 and an estimated 600,000 deaths [1]. Following diagnosis of breast cancer, patients are stratified based on expression of estrogen receptor alpha (ERα), progesterone receptor (PR), and amplification of the human epidermal growth factor receptor 2 (HER2) gene. Triple negative breast cancer (TNBC) is a term used to describe breast cancers which are ERα/PR negative and lack amplification of the HER2 gene. Is subset is associated with the poorest outcomes among breast cancers, with higher mortality rates compared to other subtypes, despite accounting for only 15–20% of cases [2]. Given the lack of biomarkers to guide treatment, first line therapy for TNBC is a regimen of adjuvant and increasingly neoadjuvant, cytotoxic chemotherapy consisting of anthracyclines and taxanes. Despite the high rates of mortality, TNBC has higher response rates to chemotherapy compared to other breast cancers. Patients who achieve a complete pathological response (pCR) tend to have a very good prognosis and survival rates
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