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Breast Cancer Research
Published in: Breast Cancer Research 4/2014

Open Access 01-08-2014 | Research article

Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ

Authors: Laura G Estévez, Ana Suarez-Gauthier, Elena García, Cristina Miró, Isabel Calvo, María Fernández-Abad, Mercedes Herrero, Manuel Marcos, Cristina Márquez, Fernando Lopez Ríos, Sofía Perea, Manuel Hidalgo

Published in: Breast Cancer Research | Issue 4/2014

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Abstract

Introduction

Human epidermal growth factor receptor 2 (HER2) amplification is frequent in ductal carcinoma in situ (DCIS) of the breast and is associated with poorly differentiated tumors and adverse prognosis features. This study aimed to determine the molecular effects of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS.

Methods

Patients with HER2 positive DCIS received 1,500 mg daily of lapatinib for four consecutive weeks prior to surgical resection. Magnetic resonance imaging (MRI) was used to determine changes in tumor volume. The molecular effects of lapatinib on HER2 signaling (PI3K/AKT and RAS/MAPK pathways), cell proliferation (Ki67 and p27) and apoptosis (TUNEL) were determined in pre and post-lapatinib treatment samples.

Results

A total of 20 patients were included. Lapatinib was well tolerated with only minor and transient side effects. The agent effectively modulated HER2 signaling decreasing significantly pHER2 and pERK1 expression, together with a decrease in tumor size evaluated by MRI. There was no evidence of changes in Ki67.

Conclusions

Four weeks of neoadjuvant lapatinib in patients with HER2-positive DCIS resulted in inhibition of HER2 and RAS/MAPK signaling pathway.

Trial registration

2008-004492-21 (Registered June 25th 2008).
Appendix
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Metadata
Title
Molecular effects of lapatinib in patients with HER2 positive ductal carcinoma in situ
Authors
Laura G Estévez
Ana Suarez-Gauthier
Elena García
Cristina Miró
Isabel Calvo
María Fernández-Abad
Mercedes Herrero
Manuel Marcos
Cristina Márquez
Fernando Lopez Ríos
Sofía Perea
Manuel Hidalgo
Publication date
01-08-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3695

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