Background: HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the 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.

HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: a systematic review and meta-analysis

Rognoni, Carla;
2020

Abstract

Background: HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the 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.
2020
2020
Schettini, Francesco; Pascual, Tomás; Conte, Benedetta; Chic, Nuria; Brasó-Maristany, Fara; Galván, Patricia; Martínez, Olga; Adamo, Barbara; Vidal, Maria; Muñoz, Montserrat; Fernández-Martinez, Aranzazu; Rognoni, Carla; Griguolo, Gaia; Guarneri, Valentina; Conte, Pier Franco; Locci, Mariavittoria; Brase, Jan C; Gonzalez-Farre, Blanca; Villagrasa, Patricia; De Placido, Sabino; Schiff, Rachel; Veeraraghavan, Jamunarani; Rimawi, Mothaffar F; Osborne, C Kent; Pernas, Sonia; Perou, Charles M; Carey, Lisa A; Prat, Aleix
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11565/4024345
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