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High serum TGF-alpha predicts poor response to lapatinib and capecitabine in HER2-positive breast cancer

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Authors
Rhee, Jiyoung; Han, Sae-Won; Cha, Yongjun; Ham, Hye Seon; Kim, Hwang-phill; Oh, Do-Youn; Im, Seock-Ah; Park, Jong-Wan; Ro, Jungsil; Lee, Keun Seok; Park, In Hae; Im, Young-Hyuck; Bang, Yung-Jue; Kim, Tae-You
Issue Date
2011-01
Citation
Breast Cancer Research and Treatment, Vol.125 No.1, pp.107-114
Keywords
Breast cancerLapatinibTransforming growth factor-alpha
Abstract
Lapatinib and capecitabine combination therapy is effective in trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the biomarkers from serum of patients receiving lapatinib and capecitabine Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 mg/m(2)/day, day 1-14, every 3 weeks. Serum samples were obtained before treatment initiation. Levels of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), extracellular domains of EGFR and HER2 were measured by enzyme-linked immunosorbent assay. The effect of TGF-alpha on in vitro sensitivity of SK-BR-3 cells to lapatinib was investigated. Sixty-four patients were included. Response rate was significantly higher in patients with low serum TGF-alpha (a parts per thousand currency sign3.75 pg/ml) compared to high TGF-alpha (> 3.75 pg/ml) [61.1% (11/18) vs. 17.4% (8/46), respectively; P = 0.001]. Low serum TGF-alpha was independently associated with better response in multivariate analysis [adjusted odds ratio, 8.96; 95% confidence interval (CI) 2.4-34.2]. Time-to-progression tended to be shorter in patients with high serum TGF-alpha compared to low TGF-alpha [median 3.8 months (95% CI 2.3-5.4) vs. 6.5 (95% CI 6.1-6.8), respectively; P = 0.067]. We confirmed that TGF-alpha diminished the sensitivity of SK-BR3-cells to lapatinib in vitro. The in vitro antiproliferative effect of cetuximab in combination with lapatinib was higher than that of lapatinib alone in SK-BR3-cells exposed to TGF-alpha. These data suggest that TGF-alpha plays a role in resistance to lapatinib and capecitabine therapy among HER2-positive breast cancer.
ISSN
0167-6806
URI
https://hdl.handle.net/10371/172993
DOI
https://doi.org/10.1007/s10549-010-1200-9
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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