ESR1, PGR, ERBB2, and MKi67 mRNA expression in postmenopausal women with hormone receptor-positive early breast cancer: results from ABCSG Trial 6

M Filipits,M Rudas,C.F Singer,F Fitzal,Z Bago-Horvath,R Greil,M Balic,S.F Lax,S Halper,W Hulla,N.C Wu,X Liu,J Weidler,M Bates,D Hlauschek,M Gnant,P Dubsky

doi:10.1016/j.esmoop.2021.100228

Abstract

BackgroundThe purpose of this study was to assess the concordance of real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection of ESR1, PGR, ERBB2, and MKi67 messenger RNA (mRNA) in breast cancer tissues with central immunohistochemistry (IHC) in women treated within the prospective, randomized Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6.Patients and methodsWe evaluated ESR1, PGR, ERBB2, and MKi67 mRNA expression by Xpert® Breast Cancer STRAT4 (enables cartridge-based RT-qPCR detection of mRNA in formalin-fixed paraffin-embedded tissues) and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 protein expression by IHC [in situ hybridization (ISH) for HER2 IHC 2+] in 1115 surgical formalin-fixed paraffin-embedded specimens from patients of ABCSG Trial 6. Overall percent agreement (concordance), positive percent agreement (sensitivity), and negative percent agreement (specificity) between STRAT4 and IHC were determined for each marker. The primary objective of the study was concordance between STRAT4 mRNA measurements of ESR1, PGR, ERBB2, and MKi67 with central reference laboratory IHC (and ISH for HER2 IHC 2+ cases). Time to distant recurrence was analyzed by Cox models.ResultsAll performance targets for ER, PR, and Ki67 were met. For HER2, the negative percent agreement target but not the positive percent agreement target was met. Concordance between STRAT4 and IHC was 98.9% for ER, 89.9% for PR, 98.2% for HER2, and 84.8% for Ki67 (excluding intermediate IHC 10%-20% staining). In univariable and multivariable Cox regression analyses, all four biomarkers tested by either STRAT4 RT-qPCR or by central IHC (ISH) had a comparable time to distant recurrence indicating similar prognostic value.ConclusionsWith the exception of HER2, we demonstrate high concordance between centrally assessed IHC and mRNA measurements of ER, PR, and Ki67 as well as a high correlation of the two methods with clinical outcome. Thus, mRNA-based assessment by STRAT4 is a promising new tool for diagnostic and therapeutic decisions in breast cancer.

Highlights

In early breast cancer, therapeutic decisions are based on a number of clinical and pathological factors, including the expression of biomarkers with established clinical utility and validity such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and a cellular marker for proliferation (Ki67)
Paraffin blocks with sufficient tumor quality were available from 1115 of the 2020 patients who were included in ABCSG Trial 6 and in whom long-term outcome data were available
These 1115 patients were similar in age, tumor size, nodal status, tumor grade, and type of surgery compared with the 905 patients without available tumor blocks, but ER and PR expression of their tumors, and randomized treatment arm differed statistically significant between the two groups

Summary

Introduction

Therapeutic decisions are based on a number of clinical and pathological factors, including the expression of biomarkers with established clinical utility and validity such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and a cellular marker for proliferation (Ki67).

Objectives

Results

Conclusion