HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade Journal Article


Authors: Prat, A.; Pascual, T.; De Angelis, C.; Gutierrez, C.; Llombart-Cussac, A.; Wang, T.; Cortés, J.; Rexer, B.; Paré, L.; Forero, A.; Wolff, A. C.; Morales, S.; Adamo, B.; Brasó-Maristany, F.; Vidal, M.; Veeraraghavan, J.; Krop, I.; Galván, P.; Pavlick, A. C.; Bermejo, B.; Izquierdo, M.; Rodrik-Outmezguine, V.; Reis-Filho, J. S.; Hilsenbeck, S. G.; Oliveira, M.; Dieci, M. V.; Griguolo, G.; Fasani, R.; Nuciforo, P.; Parker, J. S.; Conte, P.; Schiff, R.; Guarneri, V.; Osborne, C. K.; Rimawi, M. F.
Article Title: HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade
Abstract: BACKGROUND: Identification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy. METHODS: A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated. RESULTS: A total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P < .001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P = .01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P < .001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P = .02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P = .01). CONCLUSIONS: Combining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 112
Issue: 1
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2020-01-01
Start Page: 46
End Page: 54
Language: English
DOI: 10.1093/jnci/djz042
PUBMED: 31037288
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 February 2020 -- Source: Scopus
Altmetric
Citation Impact
MSK Authors
  1. Jorge Sergio Reis
    403 Reis