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Correlation of HER2, p95HER2 and HER3 expression and treatment outcome of lapatinib plus capecitabine in HER2-positive metastatic breast cancer

Cited 20 time in Web of Science Cited 21 time in Scopus
Authors
Han, Sae-Won; Cha, Yongjun; Paquet, Agnes; Huang, Weidong; Weidler, Jodi; Lie, Yolanda; Sherwood, Thomas; Bates, Michael; Haddad, Mojgan; Park, In Hae; Oh, Do-Youn; Lee, Keun Seok; Im, Seock-Ah; Bang, Yung-Jue; Ro, Jungsil; Kim, Tae-You
Issue Date
2012-07
Citation
PLoS ONE, Vol.7 No.7, p. e0039943
Abstract
Background: Lapatinib plus capecitabine is an effective treatment option for trastuzumab-refractory HER2-positive metastatic breast cancer. We have investigated the correlation between quantitative measures of HER2, p95HER2, and HER3 and treatment outcomes using lapatinib and capecitabine. Methods: Total HER2 (H2T), p95HER2 (p95), and total HER3 (H3T) expression were quantified in formalin-fixed paraffinembedded samples using the VeraTag assays. Patients received lapatinib and capecitabine treatment following trastuzumab failure according to the Lapatinib Expanded Access Program. The association between the protein expression levels and clinical outcomes was analyzed. Results: A total of 52 patients were evaluable. H2T level was significantly higher in responders (median 93.49 in partial response, 47.66 in stable disease, and 17.27 in progressive disease; p = 0.020). Longer time-to-progression (TTP) was observed in patients with high H2T [p = 0.018, median 5.2 months in high (> 14.95) vs. 1.8 in low (< 14.95)] and high H3T [p = 0.017, median 5.0 months in high (> 0.605) vs. 2.2 in low (< 0.605)]. Patients having both high H2T and high H3T had significantly longer TTP [adjusted hazard ratio (HR) 0.38 (95% CI 0.20-0.73), p = 0.004] and overall survival [adjusted HR 0.46 (95% CI 0.24-0.89), p = 0.020]. No significant association between p95 and response or survival was observed. Conclusions: These data suggest a correlation between high HER2 and high HER3 expression and treatment outcome, while no significant difference was observed between clinical outcome and p95 expression level in this cohort of HER2-positive, trastuzumab-refractory metastatic breast cancer patients treated with lapatinib and capecitabine.
ISSN
1932-6203
URI
https://hdl.handle.net/10371/173244
DOI
https://doi.org/10.1371/journal.pone.0039943
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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