Genomic Grade Index (GGI): Feasibility in Routine Practice and Impact on Treatment Decisions in Early Breast Cancer

Otto Metzger‐Filho ,Evandro De Azambuja,Vincent Richard,Marc Buyse,Michail Ignatiadis,Michel Coibion,Virginie Fasolo,Stefan Michiels,Aurélie Catteau,Christos Sotiriou,Kamal S Saini,Peter Vuylsteke,Nathalie Cornez,Martine Piccart,Brigitte Vanderschueren,Sihem Naji,Denis Larsimont,Jean Luc Canon,Jean Pierre Kains,D Faverly ,P Cusumano ,Hélène Peyro‐Saint‐Paul ,P Delrée ,Véronique Jossa

doi:10.1371/journal.pone.0066848

Abstract

PurposeGenomic Grade Index (GGI) is a 97-gene signature that improves histologic grade (HG) classification in invasive breast carcinoma. In this prospective study we sought to evaluate the feasibility of performing GGI in routine clinical practice and its impact on treatment recommendations.MethodsPatients with pT1pT2 or operable pT3, N0-3 invasive breast carcinoma were recruited from 8 centers in Belgium. Fresh surgical samples were sent at room temperature in the MapQuant Dx™ PathKit for centralized genomic analysis. Genomic profiles were determined using Affymetrix U133 Plus 2.0 and GGI calculated using the MapQuant Dx® protocol, which defines tumors as low or high Genomic Grade (GG-1 and GG-3 respectively).Results180 pts were recruited and 155 were eligible. The MapQuant test was performed in 142 cases and GGI was obtained in 78% of cases (n=111). Reasons for failures were 15 samples with <30% of invasive tumor cells (11%), 15 with insufficient RNA quality (10%), and 1 failed hybridization (<1%). For tumors with an available representative sample (≥ 30% inv. tumor cells) (n=127), the success rate was 87.5%. GGI reclassified 69% of the 54 HG2 tumors as GG-1 (54%) or GG-3 (46%). Changes in treatment recommendations occurred mainly in the subset of HG2 tumors reclassified into GG-3, with increased use of chemotherapy in this subset.ConclusionThe use of GGI is feasible in routine clinical practice and impacts treatment decisions in early-stage breast cancer.Trial Registration ClinicalTrials.gov NCT01916837, http://clinicaltrials.gov/ct2/show/NCT01916837

Highlights

Integrating the results of genomic tests with classic clinicopathologic variables to make treatment decisions represents a major advance in early breast cancer [1]
Several gene expression signatures have been developed with the aim of refining the prognosis of patients diagnosed with this disease [1]
The present study prospectively evaluated both the feasibility of implementing Genomic Grade Index (GGI) in eight community-based hospitals and the impact of GGI results on treatment decisions

Summary

Introduction

Integrating the results of genomic tests with classic clinicopathologic variables to make treatment decisions represents a major advance in early breast cancer [1]. Retrospective analyses have demonstrated the ability of genomic signatures to classify patients into risk categories, thereby adding prognostic value to classic clinico-pathologic variables [2,3,4]. Such signatures provide predictive information, identifying the subgroups of patients most likely to benefit from therapeutic interventions such as chemotherapy [5,6]. As for any practicechanging technology, a careful evaluation of the logistics associated with its use is needed in order to ensure future applicability This is true for molecular assays requiring fresh or frozen tumor samples, which add complexity to routine surgical and pathology procedures

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