Abstract PO3-16-03: Investigating HER2DX genomic assay concordance within HER2-positive breast cancer
Authors: Brasó-Maristany Fara , Paré Laia , Villacampa Guillermo , Marín-Aguilera Mercedes , Spellman Paul , Waks Adrienne , Krop Ian , Sanfeliu Esther , Li Zhequi , Galván Patricia , Hernández-Illán Eva , Jares Pedro , Puig-Butillé Joan Antón , Vivancos Ana , Villagrasa Patricia , Parker Joel S. , Perou Charles M. , Tolaney Sara , Metzger Otto , Polyak Kornelia , Prat Aleix 
Published: May 2024

Abstract
Background: The HER2DX genomic assay, encompassing a 27-gene panel, provides prognostic (risk-score) and predictive (pathological complete response [pCR]-score) information while quantifying ERBB2 mRNA expression (ERBB2-score). This study aims to explore the variability of HER2DX scores within tumor samples and between paired diagnostic biopsies and surgical specimens. Methods: The standardized HER2DX assay was conducted on pretreatment FFPE biopsies from two distinct geographical areas within tumors (i.e., two different core biopsies) of patients enrolled in the 14-409 phase II study. This study assessed the impact of HER2 heterogeneity on treatment response in stage II-III HER2+ breast cancer patients treated with neoadjuvant T-DM1 and pertuzumab. Additionally, HER2DX was evaluated on paired biopsy-surgery FFPE samples from 6 patients who underwent primary surgery without pre-operative treatment. Variability and concordance of the three HER2DX groups scores were calculated, and Pearson's correlation coefficient determined the correlation between scores at different sites/time points. Paired t-tests were performed between tumor samples for the HER2DX scores. Results: The HER2DX assay was evaluated in two different diagnostic pre-treatment core biopsies from 106 patients (n=212 HER2DX assays). Intra-tumor concordance rates of the three HER2DX groups (risk-score, pCR-score, and ERBB2-score) were 94.3%, 87.7%, and 91.5%, respectively. No significant differential expression of HER2DX scores was observed across paired core biopsies (p-values=0.327 [risk-score], 0.415 [pCR-score], and 0.451 [ERBB2-score]). The average score differences (core 1 - core 2 [scale from 0 to 100]) were 0.57 (risk-score), 0.63 (pCR score), and -0.63 (ERBB2-score). Correlation coefficients across paired core biopsies were 0.96 (risk-score), 0.91 (pCR-score), and 0.90 (ERBB2-score). Additionally, intra-patient variability of the HER2DX scores was evaluated. Average variability in risk-score was 3.38% (95% CI: 2.76-4.01), in pCR-score was 3.53% (95% CI: 2.84-4.23) and in ERBB2 was 3.87% (95% CI: 2.97-4.77). In 6 patients with cT1-2 cN0 disease, HER2DX was evaluated in a diagnostic core biopsy and a surgical specimen, with an average time interval of 8.5 weeks (range 4 to 12 weeks) between time points. The intra-patient concordance rates of the three HER2DX groups were 83.3%, 83.3%, and 100% for risk-score, pCR-score, and ERBB2-score, respectively. No significant differential expression of HER2DX scores was found across paired biopsy-surgery samples (p-values=0.814 [risk-score], 0.128 [pCR-score], and 0.607 [ERBB2-score]). The average score differences (core biopsy - surgical specimen [scale from 0 to 100]) were -0.67 (risk-score), -11.5 (pCR score), and 2 (ERBB2-score). Correlation coefficients across paired HER2DX assays were 0.97 (risk-score), 0.87 (pCR-score), and 0.94 (ERBB2-score). Conclusion: The HER2DX genomic assay demonstrates low variability within HER2+ breast cancer, supporting its reliability as a consistent tool for assessing prognosis, the probability of pCR and ERBB2 quantitative expression.
Citation Format: Fara Brasó-Maristany, Laia Paré, Guillermo Villacampa, Mercedes Marín-Aguilera, Paul Spellman, Adrienne Waks, Ian Krop, Esther Sanfeliu, Zhequi Li, Patricia Galván, Eva Hernández-Illán, Pedro Jares, Joan Antón Puig-Butillé, Ana Vivancos, Patricia Villagrasa, Joel S. Parker, Charles M. Perou, Sara Tolaney, Otto Metzger, Kornelia Polyak, Aleix Prat. Investigating HER2DX genomic assay concordance within HER2-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-03.