A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study

C.A Drukker,V.P Retèl,W.H Harten,J.M Bueno‐De‐Mesquita,M Knauer,E.J.T Rutgers,L.J Veer,S.C Linn,H Tinteren,G.S Sonke,M.J Vijver,R.M.H Roumen,J Wesseling

doi:10.1002/ijc.28082

Abstract

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1–3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n = 219) and high-risk (n = 208) patients were 97.0% and 91.7%. The 5-year DRFI probabilities for AOL low-risk (n = 132) and high-risk (n = 295) patients were 96.7% and 93.4%. For 70-gene signature low-risk–AOL high-risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.

Highlights

Over the last two decades breast cancer mortality has declined in Western countries
adjuvant systemic therapy (AST) and outcome stratified by 70-gene signature Supporting Information Table 1 summarizes the patient characteristics defined by the result of the 70-gene signature as reported by Bueno-de-Mesquita et al.6 70-gene signature high-risk patients more often had large, poorly differentiated, estrogen receptor (ER) negative, progesterone receptor (PR) negative and HER2 positive tumors than 70-gene signature low-risk patients
The RASTER study provides the first prospective data on the outcome of patients with breast cancer for whom a gene expression prognosis classifier was used to determine the need for adjuvant systemic treatment

Summary

Introduction

Over the last two decades breast cancer mortality has declined in Western countries. This decline has been ascribed to early detection due to the implementation of population-based mammographic screening programs and the introduction of adjuvant systemic therapy (AST).[1]. The microarRAy prognoSTics in breast cancER (RASTER) study was conducted in 16 community hospitals in the Netherlands.[6] The primary aim of this multicenter observational study was to assess the feasibility of implementing the 70-gene signature in a community-based setting and to study the clinical impact of the 70-gene signature test result on AST decision making.[6] A secondary aim of the RASTER study was to assess the outcome of patients for whom a gene expression classifier was used to determine the need for adjuvant systemic treatment. A considerable discrepancy in risk estimations among different clinicopathological guidelines and the 70-gene signature was observed.[6] The addition of the 70-gene signature test result to standard clinicopathological factors led to a change in AST advice in 19% of patients.[6] Here, we report the 5-year follow-up data of the RASTER study

Methods

Results

Conclusion