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

被引：9

作者：

Duchnowska, Renata ^{[1
]}

Wysocki, Piotr J. ^{[2
]}

Korski, Konstanty ^{[3
]}

Czartoryska-Arlukowicz, Bogumila ^{[4
]}

Niwinska, Anna ^{[5
,6
]}

Orlikowska, Marlena ^{[7
]}

Radecka, Barbara ^{[8
]}

Studzinski, Maciej ^{[9
]}

Demlova, Regina ^{[10
]}

Ziolkowska, Barbara ^{[11
]}

Merdalska, Monika ^{[12
]}

Hajac, Lukasz ^{[13
]}

Mysliwiec, Paulina ^{[14
]}

Zuziak, Dorota ^{[15
]}

Debska-Szmich, Sylwia ^{[16
]}

Lang, Istvan ^{[17
]}

Foszczynska-Kloda, Malgorzata ^{[2
]}

Karczmarek-Borowska, Bozenna ^{[18
]}

Zawrocki, Anton ^{[19
]}

Kowalczyk, Anna ^{[19
]}

Biernat, Wojciech ^{[19
]}

Jassem, Jacek ^{[19
]}

机构：

[1] Mil Inst Med, Dept Oncol, Warsaw, Poland

[2] West Pomeranian Canc Ctr, Szczecin, Poland

[3] Greater Poland Canc Ctr, Poznan, Poland

[4] Bialystok Oncol Ctr, Bialystok, Poland

[5] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland

[6] Inst Oncol, Warsaw, Poland

[7] Warmia & Masuria Oncol Ctr, Olsztyn, Poland

[8] Opole Oncol Ctr, Warsaw, Poland

[9] Ctr Oncol, Bydgoszcz, Poland

[10] Masaryk Mem Canc Inst, Brno, Czech Republic

[11] Reg Hosp, Chemotherapy Dept, Wroclaw, Poland

[12] Ctr Oncol, Kielce, Poland

[13] Ctr Oncol, Wroclaw, Poland

[14] Ctr Oncol, Zielona Gora, Poland

[15] Ctr Oncol, Bielsko Biala, Poland

[16] Med Univ Lodz, Lodz, Poland

[17] Natl Inst Oncol, Dept Med Oncol, Budapest, Hungary

[18] Subcarpathian Oncol Ctr, Dept Chemotherapy, Rzeszow, Poland

[19] Med Univ Gdansk, Gdansk, Poland

来源：

ONCOTARGET | 2016年 / 7卷 / 01期

关键词：

breast cancer; epidermal growth factor receptor type 2; lapatinib; mTOR; p-MAPK; ACTIVATED PROTEIN-KINASE; ESTROGEN-RECEPTOR STATUS; PI3K PATHWAY ACTIVATION; TRASTUZUMAB RESISTANCE; TENSIN HOMOLOG; CYCLIN-E; ADJUVANT CHEMOTHERAPY; ANTITUMOR-ACTIVITY; GROWTH; CELLS;

D O I：

10.18632/oncotarget.6375

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：550 / 564

页数：15

共 61 条

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