Immunohistochemical prediction of lapatinib efficacy in advanced HER2-positive breast cancer patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F16%3AN0000060" target="_blank" >RIV/00209805:_____/16:N0000060 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/16:00093105

Result on the web

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808017" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808017</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.18632/oncotarget.6375" target="_blank" >10.18632/oncotarget.6375</a>

Result language

angličtina

Original language name

Immunohistochemical prediction of lapatinib efficacy in advanced HER2-positive breast cancer patients

Original language description

Molecular mechanisms of lapatinib resistance in breast cancer are not well understood. The aim of this study was to correlate expression of selected proteins involved in ErbB family signaling pathways with clinical efficacy of lapatinib. Study group included 270 HER2-positive advanced breast cancer patients treated with lapatinib and capecitabine. Immunohistochemical expression of phosphorylated adenosine monophosphate-activated protein (p-AMPK), mitogen-activated protein kinase (p-MAPK), phospho (p)-p70S6K, cyclin E, phosphatase and tensin homolog were analyzed in primary breast cancer samples. The best discriminative value for progression-free survival (PFS) was established for each biomarker and subjected to multivariate analysis. At least one biomarker was determined in 199 patients. Expression of p-p70S6K was independently associated with longer (HR 0.45; 95% CI: 0.25–0.81; p = 0.009), and cyclin E with shorter PFS (HR 1.83; 95% CI: 1.06–3.14; p = 0.029). Expression of p-MAPK (HR 1.61; 95% CI 1.13–2.29; p = 0.009) and cyclin E (HR 2.99; 95% CI: 1.29–6.94; p = 0.011) was correlated with shorter, and expression of estrogen receptor (HR 0.65; 95% CI 0.43–0.98; p = 0.041) with Langer overall survival. Expression of p-AMPK negatively impacted response to treatment (HR 3.31; 95% CI 1.48–7.44; p = 0.004) and disease control (HR 3.07; 95% CI 1.25–7.58; p = 0.015). In conclusion: the efficacy of lapatinib seems to be associated with the activity of downstream signaling pathways – AMPK/mTOR and Ras/Raf/MAPK. Further research is warranted to assess the clinical utility of these data and to determine a potential role of combining lapatinib with MAPK pathway inhibitors.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FD - Oncology and haematology

OECD FORD branch

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Project

<a href="/en/project/LM2015090" target="_blank" >LM2015090: Czech National Node to the European Clinical Research Infrastructure Network</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Oncotarget

ISSN

1949-2553

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

550-564

UT code for WoS article

000369950300042

EID of the result in the Scopus database

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