Abstract
Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells. Analysing these changes has the potential to improve the prediction of which specific patients will respond to endocrine treatment. Serially profiled biopsies during treatment in the neoadjuvant setting offer promise for accurate and early prediction of response to both current and novel drugs and allow investigation of mechanisms of resistance. In addition, recent advances in monitoring tumour evolution through non-invasive (liquid) sampling of circulating tumour cells and cell-free tumour DNA may provide a method to detect resistant clones and allow implementation of personalized treatments for metastatic breast cancer patients. This review summarises current and future biomarkers and signatures for predicting response to endocrine treatment, and discusses the potential for using approved drugs and novel agents to improve outcomes. Increased prediction accuracy is likely to require sequential sampling, utilising preoperative or neoadjuvant treatment and/or liquid biopsies and an improved understanding of both the dynamics and heterogeneity of breast cancer.
Highlights
Breast cancer is the most common cancer in women and second most common cancer worldwide [1]
The neoadjuvant setting to predict endocrine treatment response Short-term pre-operative trials with specific groups of patients have proved promising in identifying predictive biomarkers of the efficacy of anti-cancer-targeted therapies [47]
Evidence of endocrine drug effectiveness can be obtained in the pre-operative setting by profiling baseline and on-treatment biopsy samples utilising the window-of-opportunity. This predictive evidence acquired during short-term neoadjuvant therapy can help to identify individual patients that will potentially benefit from long-term adjuvant treatment enabling personalized approaches
Summary
Breast cancer is the most common cancer in women and second most common cancer worldwide [1]. The use of endocrine therapy in the neoadjuvant setting has allowed clinicians to detect patients that benefit from treatment over a short-term period by simultaneously monitoring tumour volume. We discuss the current and potential future of endocrine treatment response prediction and biomarkers for individualization of breast cancer therapy in patients with ER+ cancers.
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