Contribution of the Prosigna® (PAM50) Gene Signature Assay as a New-generation Genomic Test for Treatment Decision-making in Early Breast Cancer

Abstract

The Prosigna® Breast Cancer Prognostic Gene Signature Assay is based on the characterisation of 50 genes relevant to breast cancer biology and provides intrinsic subtype identification based on the individual tumour biology, a prognostic risk of recurrence (ROR) score and a risk group classification, for each individual patient tested. The Prosigna assay is indicated for post-menopausal women with early-stage hormone receptor-positive breast cancer with or without nodal involvement. Running on the NanoString nCounter® DX Analysis system, which allows direct digital counting of target molecules, the assay offers a simple, reproducible and reliable method to profile many genes simultaneously with high sensitivity and precision. The Prosigna Breast Cancer Prognostic Gene Signature Assay has received 510(k) clearance from the US Food and Drug Administration. It has also received a CE mark and is available for use, among other geographical areas, in the EU, Israel and parts of the Middle East, through qualified local pathology laboratories. The de-centralised testing enables timely result delivery and direct interaction between the laboratory pathologists and treating physicians. The analytical reproducibility, precision and robustness of Prosigna have been demonstrated. Moreover, it has been clinically validated in two independent prospectiveretrospective studies using >2,400 samples from post-menopausal patients enrolled in the Austrian Breast & Colorectal Cancer Study Group 8 (ABCSG 8) and Arimidex, Tamoxifen Alone or Combined (ATAC) trials (Level 1B Evidence). These validation studies show that Prosigna identifies a clinically relevant low-risk subgroup among both node-negative and node-positive patients with 1-3 involved lymph nodes. Moreover, the ROR score predicts risk of late distant recurrence as well as for high risk of local recurrence. Prosigna thus can offer clinically relevant information, which may help guide treatment decision-making in early breast cancer.