Elsevier

The Breast

Volume 22, Issue 1, February 2013, Pages 1-12
The Breast

Review
Efficacy of HER2-targeted therapy in metastatic breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors

https://doi.org/10.1016/j.breast.2012.09.008Get rights and content
Under a Creative Commons license
open access

Abstract

Therapies targeting the human epidermal growth factor receptor (HER) 2 are effective in metastatic breast cancer (MBC).

We review the efficacy of HER2-directed therapies, focussing on monoclonal antibodies and tyrosine kinase inhibitors targeting HER2 that have been tested in phase II–III studies in MBC.

Trastuzumab is an important component of first-line treatment of HER2-positive MBC. New anti-HER2 drugs have the potential to change clinical practice. The potential role of the different drugs and regimens is yet to be determined. The response rate for trastuzumab-DM1 of 26–64% is comparable to those obtained for capecitabine plus lapatinib (48%), continuing trastuzumab in combination with capecitabine (48%), pertuzumab plus trastuzumab (24%), and neratinib (24%). Strategies combining multiple HER2-directed therapies might yield additive or synergistic effects and lead to improved outcome.

The future challenges include understanding HER2 functions, designing rational combinations and optimal selection of patients.

Keywords

Breast cancer
Human epidermal growth factor receptor
Lapatinib
Targeted therapy
Trastuzumab

Abbreviations

AMP
adenosine monophosphate
CBR
clinical benefit rate
CI
confidence interval
CR
complete response
EGFR
epidermal growth factor receptor
ER
estrogen receptor
FISH
fluorescent in situ hybridization
HER
human epidermal growth factor receptor
HR
hazard ratio
IHC
immunohistochemistry
LVEF
left ventricular ejection fraction
MAPK
mitogen-activated protein kinases
MBC
metastatic breast cancer
mTOR
mammalian target of rapamycin
pCR
pathological complete response
PFS
progression free survival
PI3K
phosphatidylinositol 3-kinase
PR
partial response
SD
stable disease
TGFα
transforming growth factor α
TKI
tyrosine kinase inhibitor
TTP
time to progression
OS
overall survival

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