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

Varování

Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.

Autoři	DUCHNOWSKA Renata WYSOCKI Piotr J. KORSKI Konstanty CZARTORYSKA-ARŁUKOWICZ Bogumiła NIWIŃSKA Anna ORLIKOWSKA Marlena RADECKA Barbara STUDZIŃSKI Maciej DEMLOVÁ Regina ZIÓŁKOWSKA Barbara MERDALSKA Monika HAJAC Łukasz MYŚLIWIEC Paulina ZUZIAK Dorota DĘBSKA-SZMICH Sylwia LANG Istvan FOSZCZYŃSKA-KŁODA Małgorzata KARCZMAREK-BOROWSKA Bożenna ŻAWROCKI Anton KOWALCZYK Anna BIERNAT Wojciech JASSEM Jacek
Rok publikování	2016
Druh	Článek v odborném periodiku
Časopis / Zdroj	Oncotarget
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://www.oncotarget.com/article/22027/text/
Doi	http://dx.doi.org/10.18632/oncotarget.6375
Obor	Onkologie a hematologie
Klíčová slova	breast cancer; epidermal growth factor receptor type 2; lapatinib; mTOR; p-MAPK
Popis	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 longer 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.
Související projekty:	CZECRIN - Český národní uzel Evropské sítě infrastruktur klinického výzkumu