A clinical validation study of MammaPrint in hormone receptor-positive breast cancer from the Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG-8) biomarker cohort.

BACKGROUND

MammaPrint is a prognostic assay based on gene expression in tumors from patients with early breast cancer. MammaPrint has been extensively validated and Food and Drug Administration cleared in fresh and formalin-fixed and paraffin-embedded (FFPE) tissue. We aimed to assess its prognostic performance in the biomarker cohort of the Austrian Breast and Colorectal Cancer Study Group 8 (ABCSG-8) patient population, and to obtain a higher level of evidence with regard to its clinical validity after RNA extraction from FFPE biobank tissue.

PATIENTS AND METHODS

A prespecified retrospective analysis to test the prognostic performance of the MammaPrint test to predict distant recurrence-free survival at 5 and 10 years as primary end point was carried out. MammaPrint risk, clinicopathological factors (after central pathological review), and clinical risk (using a modified version of Adjuvant! Online) were evaluated by Cox regression analyses.

RESULTS

From 1347 available samples, 607 (45%) failed quality control after RNA extraction. In total, 658 (49%) patients were included in survival analyses: MammaPrint low risk versus high risk is a significant prognostic factor for distant recurrence-free survival at 5 years (94.0% versus 91.6%) with a significant risk reduction of 6.5% at 10 years (log-rank P value = 0.017, low risk 91.3% versus high risk 84.8%). The multivariable models suggest that hazard ratio (HR) is primarily driven by tumor stage (5-year HR 3.89; confidence interval 1.97-7.71) and nodal status (5-year HR 1.73; confidence interval 0.91-3.21). After adjustment for clinical risk groups, MammaPrint HRs remain stable with values just below 2.0 after the first 3 years.

CONCLUSIONS

The MammaPrint test showed significant prognostic performance at 5 and 10 years of follow-up. In the particular cohort of ABCSG-8, the statistical independence from clinically assessed covariates remains unclear, and no conclusions concerning the clinical validity of the test can be drawn.

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure PD reports that funding for this project was provided by Agendia to ABCSG.research in the framework of ‘Gene Expression Analysis to investigate survival outcomes in ER+ breast cancers: GiAntEss’, grants from Cepheid/Danaher and Myriad during the conduct of the study. LVV reports personal fees, a part-time employment, and is stakeholder at Agendia NV during the conduct of the study. MG reports personal fees/travel support from Amgen, Daiichi Sankyo, AstraZeneca, Eli Lilly, Lifebrain, NanoString, Novartis, TLC Biopharmaceuticals; an immediate family member is employed by Sandoz. ZB-H reports personal fees and other from Roche, and personal fees from Novartis, Biomedica outside the submitted work. RG reports personal fees from Celgene, Roche, Merck, Takeda, Astra Zeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, and Janssen C outside the submitted work. EL reports his employment in Medical Affairs by Agendia. GR reports personal fees from Pierre Fabre, Eli Lilly, AstraZeneca, personal fees and nonfinancial support from Roche, Novartis, Pfizer, Amgen, and nonfinancial support from Bristol-Myers Squibb outside the submitted work. WH reports personal fees from Roche Austria GmbH, MSD, Bioproducts GmbH, Boehringer Ingelheim and Biomedica Medizinprodukte GmbH outside the submitted work. DE reports personal fees from AstraZeneca, Novartis, Myriad, MSD, Roche, Pfizer outside the submitted work. CD reports to work as a consultant for Agendia. MF reports personal fees from AstraZeneca, Bayer, Biomedica, Bio-Rad, Boehringer Ingelheim, Myriad Genetics Inc., Pfizer and Roche outside the submitted work. The remaining authors have declared no conflicts of interest.