Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer: Intratumoral heterogeneity and DCIS or normal tissue components are unlikely to be the cause of discordance

Giuseppe Viale, Leen Slaets, Femke A. de Snoo, Jan Bogaerts, Leila Russo, Laura van’t Veer, Emiel J T Rutgers, Martine J. Piccart-Gebhart, Lisette Stork-Sloots, Patrizia Dell’Orto, Annuska M. Glas, Fatima Cardoso

Research output: Contribution to journalArticle

Abstract

Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.

Original languageEnglish
Pages (from-to)463-469
Number of pages7
JournalBreast Cancer Research and Treatment
Volume155
Issue number3
DOIs
Publication statusPublished - Feb 1 2016

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Keywords

  • Breast cancer
  • Concordance
  • ER
  • Gene expression
  • HER2
  • Hormone receptor
  • IHC/FISH
  • PgR
  • TargetPrint
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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