A Review of Gene Expression Profiling in Early-Stage ER+/HER2- Breast Cancer With A Focus on The PAM50 Risk of Recurrence Assay

Abstract

In patients with breast cancer, the expression of oestrogen receptor, progesterone receptor, and human epidermal growth factor 2 (HER2) is used as a molecular marker to determine prognosis and direct treatment decisions; however, this does not fully reflect the molecular complexity of the disease. Patients with early-stage hormone receptor-positive (ER+), HER2-negative (HER2-) breast cancer are typically treated with surgery, followed by adjuvant systemic endocrine therapy with or without adjuvant radiation therapy. Gene expression profiling assays complement clinicopathological parameters, such as tumour size, grade, and nodal status, and can be used to classify risk of recurrence, thereby informing adjuvant therapy decision-making in early-stage breast cancer to prevent unnecessary treatment with chemotherapy in low risk patients. In this review, the authors evaluate the evidence to date supporting the use of one of the tests, the Prosigna PAM50 risk of recurrence assay (Nanostring, Seattle, Washington, USA), as a prognostic tool in ER+/HER2- early-stage breast cancer, and summarise findings from a clinical and cost-effectiveness analysis performed by the National Institute for Health and Care Excellence (NICE) in the UK. The authors also focus on recommendations from regulatory bodies and key ongoing research efforts to address the remaining uncertainty regarding the application of available genomic signatures in ER+/HER2- early-stage breast cancer.