Genomic Grade Index (GGI): feasibility in routine practice and impact on treatment decisions in early breast cancer

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

Abstract

Purpose: Genomic 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.

Methods: Patients 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).

Results: 180 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.

Conclusion: The use of GGI is feasible in routine clinical practice and impacts treatment decisions in early-stage breast cancer.

Trial registration: ClinicalTrials.gov NCT01916837, https://ichgcp.net/clinical-trials-registry/NCT01916837.

Conflict of interest statement

Competing Interests: The authors have the following interests. Ipsogen SA provided financial support for the conduct of this study and is the employer of Aurélie Catteau, Virginie Fasolo, Sihem Naji and Hélčne Peyro-Saint-Paul. Drs. Sotiriou and Piccart are co-inventors of patent and patent applications on the CGI owned by Universite Libre de Bruxelles and licensed to Ipsogen SA. Virginie Fasolo is co-inventor of patent applications jointly owned by Universite Libre de Bruxelles and Ipsoegn SA and licensed to Ipsogen SA. The name of the Patent is "METHODS FOR THE DIAGNOSIS, THE DETERMINATION OF THE GRADE OF A SOLID TUMOR AND THE PROGNOSIS OF A SUBJECT SUFFERING FROM CANCER". There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Flow diagram of enrolled patients.
Figure 1. Flow diagram of enrolled patients.
Abbreviations: inv, invasive; N, nodal status.
Figure 2. Impact of GGI reclassification on…
Figure 2. Impact of GGI reclassification on treatment decisions in ER+ and HER2-negative and HG2 early-stage breast cancer.
Abbreviations: CP, treatment decision based on clinico-pathologic characteristics; CHT, chemotherapy plus hormonotherapy; HT, hormonotherapy; final, final treatment decision based on GG results and discussion with patient.

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