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

• Published in: ESMO open 2021-02, Vol.6 (1), p.100006-100006, Article 100006
• Main Authors: Dubsky, P., Van't Veer, L., Gnant, M., Rudas, M., Bago-Horvath, Z., Greil, R., Lujinovic, E., Buresch, J., Rinnerthaler, G., Hulla, W., Moinfar, F., Egle, D., Herz, W., Dreezen, C., Frantal, S., Filipits, M.
• Format: Article
• Language: English
• Subjects: ABCSG-8; clinical validation; early breast cancer; ER-positive/HER2-negative; MammaPrint; Original Research; prognostic biomarkers
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2020.100006

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. 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. 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. 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. •MammaPrint is a prognostic assay based on gene expression in tumors from patients with early breast cancer.•MammaPrint has been extensively and successfully validated- but mostly in fresh tissue.•We aimed to assess its prognostic performance in FFPE tissue from the ABCSG 8 biomarker cohort.•The MammaPrint test showed significant prognostic performance at 5 and 10 years of follow-up.•The statistical independence from clinically assessed covariates is unclear- the clinical validity in ABCSG 8 uncertain.