Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer

被引：1

作者：

Marin-Aguilera, M. ^{[1
]}

Jares, P. ^{[2
,3
]}

Sanfeliu, E. ^{[2
]}

Villacampa, G. ^{[4
,5
]}

Hernandez-lllan, E. ^{[3
]}

Martinez-Puchol, A. I. ^{[3
]}

Shankar, S. ^{[6
]}

Gonzalez-Farre, B. ^{[2
]}

Waks, A. G. ^{[6
]}

Braso-Maristany, F. ^{[1
,7
]}

Pardo, F.

Manning, D. K. ^{[6
]}

Abery, J. A. ^{[8
]}

Curaba, J. ^{[8
]}

Moon, L.

Gordon, O. ^{[8
]}

Galvan, P. ^{[1
,7
]}

Wachirakantapong, P. ^{[6
]}

Castillo, O. ^{[7
]}

Nee, C. M. ^{[6
]}

Blasco, P. ^{[7
]}

Senevirathne, T. H. ^{[6
]}

Sirenko, V. ^{[7
]}

Martinez-Saez, O. ^{[7
,9
,10
]}

Aguirre, A. ^{[7
]}

Krop, I. E. ^{[11
]}

Li, Z. ^{[12
,13
]}

Spellman, P. ^{[14
]}

Metzger Filho, O. ^{[6
,13
]}

Polyak, K. ^{[12
,13
]}

Michaels, P. ^{[6
]}

Puig-Butille, J. A. ^{[3
]}

Vivancos, A. ^{[15
]}

Matito, J. ^{[1
,15
]}

Buckingham, W. ^{[1
]}

Perou, C. M. ^{[16
]}

Villagrasa-Gonzalez, P. ^{[1
]}

Prat, A. ^{[1
,7
,9
,11
,17
]}

Parker, J. S. ^{[16
]}

Pare, L. ^{[1
]}

机构：

[1] Reveal Genom SL, Sci Dept, Carrer Villarroel 170,Escala 2,Planta 5, Barcelona 08036, Spain

[2] Hosp Clin Barcelona, Pathol Dept, Barcelona, Spain

[3] Hosp Clin Barcelona, Mol Biol Core, Barcelona, Spain

[4] SOLTI Breast Canc Res Grp, Barcelona, Spain

[5] Vall dHebron Inst Oncol, Stat Unit, Barcelona, Spain

[6] Brigham & Womens Hosp, Ctr Adv Med Diagnost, Dept Pathol, Boston, MA USA

[7] Translat Genom & Targeted Therapies Solid Tumors, IDIBAPS, Dept Pathol, Barcelona, Spain

[8] Eremid Genom Serv LLC, Kannapolis, NC USA

[9] Hosp Clin Barcelona, Med Oncol Dept, Barcelona, Spain

[10] Univ Barcelona, Dept Med, Barcelona, Spain

[11] Yale Canc Ctr, New Haven, CT USA

[12] Dana Farber Canc Inst, Boston, MA USA

[13] Harvard Med Sch, Boston, MA USA

[14] Oregon Hlth & Sci Univ, Portland, OR USA

[15] Vall dHebron Inst Oncol VHIO, Canc Genom Core, Barcelona, Spain

[16] Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC USA

[17] IOB Quiron Salud, Breast Canc Unit, Barcelona, Spain

来源：

ESMO OPEN | 2024年 / 9卷 / 03期

基金：

欧盟地平线“2020”;

关键词：

HER2DX; breast cancer; gene expression; RNA; analytical validation; OUTCOMES;

D O I：

10.1016/j.esmoop.2024.102903

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. Materials and methods: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. Results: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was <5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's k coefficients > 0.80). Conclusions: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

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页数：11

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