Portal de investigación
HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade.
Fecha de publicación:
Autores de FISABIO
Autores ajenos a FISABIO
- Prat, A
- Pascual, T
- De Angelis, C
- Gutierrez, C
- Wang, T
- Cortes, J
- Rexer, B
- Pare, L
- Forero, A
- Wolff, AC
- Morales, S
- Adamo, B
- Braso-Maristany, F
- Vidal, M
- Veeraraghavan, J
- Krop, I
- Galvan, P
- Pavlick, AC
- Bermejo, B
- Izquierdo, M
- Rodrik-Outmezguine, V
- Reis-Filho, JS
- Hilsenbeck, SG
- Oliveira, M
- Dieci, MV
- Griguolo, G
- Fasani, R
- Nuciforo, P
- Parker, JS
- Conte, P
- Schiff, R
- Guarneri, V
- Osborne, CK
- Rimawi, MF
Grupos de Investigación
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.
Datos de la publicación
- ISSN/ISSNe:
- 0027-8874, 1460-2105
- Tipo:
- Article
- Páginas:
- 46-54
- DOI:
- 10.1093/jnci/djz042
- PubMed:
- 31037288
JNCI-Journal of the National Cancer Institute OXFORD UNIV PRESS INC
Citas Recibidas en Web of Science: 123
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