The evolving role of receptors as predictive biomarkers for metastatic breast cancer

Abstract

Introduction:In breast cancer, oestrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment and the constant evolution of the disease invariably leads to resistance to treatment. Areas covered:We summarise genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis. Expert commentary:While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardise assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.

The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer

“…As with all cancer types, biomarkers with prognostic and/or predictive power are essential tools in the clinical management of this disease, with the oestrogen receptor α (ER) and the human epidermal growth factor 2 receptor (HER2) being the foremost biomarkers in BC. Assessment of both receptors to help select patients likely to respond to endocrine and HER2-targeted therapies has been established in clinical practice for many decades and has considerably improved the prognosis and survival for patients with hormone-dependent and HER2-overexpressing BC [1,2].…”

“…Despite said advances, many challenges remain in the management of BC, particularly as it pertains to advanced disease. In order to meet these needs, extensive research efforts are devoted to gaining a better understanding of the underlying complexity of the disease, as well as to identifying and validating potential molecular markers that might enable better patient stratification and treatment selection [2][3][4]. Valuable markers are typically involved in and serve as surrogates for cancer-promoting mechanisms or biological processes known to be altered by disease.…”

The Signal Transducer IL6ST (gp130) as a Predictive and Prognostic Biomarker in Breast Cancer

“…Assessment of ER and HER2 status has long been mandatory for all new BC diagnoses to help guide treatment selection [ 4 ] and has considerably improved prognosis and survival for patients with hormone-dependent and HER2-overexpressing BC. Importantly, the role of ER and HER2 as biomarkers continues to evolve, with growing evidence on different genomic aberrations contributing to the development of treatment resistance [ 5 ]. Research on ER mutations in particular has been extensive, with their prevalence and clinical implications being assessed in several retrospective and currently-ongoing prospective trials, making their translation into clinical practice in the near future a strong possibility [ 6 , 7 ].…”

Comprehensive Analysis of Splicing Factor and Alternative Splicing Event to Construct Subtype-Specific Prognosis-Predicting Models for Breast Cancer

“…Studies have been conducted extensively to demonstrate the role of AS events on BRCA. Results have shown that abnormal splicing of ER and HER2 correlated to the occurrence of BRCA; thus, it may be a potential target for cancer treatment (Inoue and Fry, 2015;Martínez-Pérez et al, 2019;Francies et al, 2020). Dysregulation of SFs has also been investigated, and results have shown that they are connected to the malignant phenotype of BRCA (Park et al, 2019).…”