Ontology highlight
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?ConclusionsCombining 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.
SUBMITTER: Prat A
PROVIDER: S-EPMC7850037 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Prat Aleix A Pascual Tomás T De Angelis Carmine C Gutierrez Carolina C Llombart-Cussac Antonio A Wang Tao T Cortés Javier J Rexer Brent B Paré Laia L Forero Andres A Wolff Antonio C AC Morales Serafín S Adamo Barbara B Brasó-Maristany Fara F Vidal Maria M Veeraraghavan Jamunarani J Krop Ian I Galván Patricia P Pavlick Anne C AC Bermejo Begoña B Izquierdo Miguel M Rodrik-Outmezguine Vanessa V Rodrik-Outmezguine Vanessa V Reis-Filho Jorge S JS Hilsenbeck Susan G SG Oliveira Mafalda M Dieci Maria Vittoria MV Griguolo Gaia G Fasani Roberta R Nuciforo Paolo P Parker Joel S JS Conte PierFranco P Schiff Rachel R Guarneri Valentina V Osborne C Kent CK Rimawi Mothaffar F MF
Journal of the National Cancer Institute 20200101 1
<h4>Background</h4>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.<h4>Methods</h4>A research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA ...[more]