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ABSTRACT: Background
HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).Methods
A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins' I2 was used to quantify heterogeneity.Results
Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I2 = 33%), in HR+ (OR = 3.61, p < 0.001, I2 = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I2 = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I2 = 0%) and in HR + disease (OR = 4.08, p = 0.001, I2 = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I2 = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I2 = 0%).Conclusions
The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.
SUBMITTER: Schettini F
PROVIDER: S-EPMC7230134 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Schettini Francesco F Pascual Tomás T Conte Benedetta B Chic Nuria N Brasó-Maristany Fara F Galván Patricia P Martínez Olga O Adamo Barbara B Vidal Maria M Muñoz Montserrat M Fernández-Martinez Aranzazu A Rognoni Carla C Griguolo Gaia G Guarneri Valentina V Conte Pier Franco PF Locci Mariavittoria M Brase Jan C JC Gonzalez-Farre Blanca B Villagrasa Patricia P De Placido Sabino S Schiff Rachel R Veeraraghavan Jamunarani J Rimawi Mothaffar F MF Osborne C Kent CK Pernas Sonia S Perou Charles M CM Carey Lisa A LA Prat Aleix A
Cancer treatment reviews 20200117
<h4>Background</h4>HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).<h4>Methods</h4>A systematic literature search was performed ...[more]