title: Overexpression of class III beta tubulin and amplified HER2 gene predict good response to paclitaxel and trastuzumab therapy.
abstract: Through this study, we aimed to validate several biomarkers that have been known to possibly predict the outcomes of the trastuzumab and paclitaxel (TP). Human epidermal growth factor 2 (HER2) positive metastatic breast cancer (MBC) patients who had been treated with TP in single institute from 2006 to 2009 were included in this study. For procured formalin fixed paraffin embedded tumor tissues, HER2 amplification index (AI) and polymorphisms of the immunoglobulin G fragment C receptors (FCGR) were assessed as biomarkers to the trastuzumab and expression of class III beta tubulin (bTubIII) was evaluated as a predictive factor to the paclitaxel. Of 46 patients treated with TP, 27 patients could be evaluated for HER2 AI, 31 for bTubIII, and 26 for FCGR gene polymorphism. The median of the HER2 AI was 5.0 (range, 1.4-15.5) and a higher HER2 AI (≥ 5.0) was significantly correlated with better response rate (RR) (80% vs. 42%, P=0.049) and longer progression-free survival (PFS) (13.6 vs. 6.9 months, P=0.023). High bTubIII expression showed higher RRs than did low expression (81% vs. 40%, P=0.040) in addition to longer PFS (16.2 months vs. 8.8 months, P=0.04). However, polymorphisms in FCGR 2A-H131R or FCGR 3A-V158F were not predictive of RR or PFS. Our results suggest that a high HER2 AI and high bTubIII expression could be predictive of the outcomes to TP therapy but no evidence was found in terms of FCGR polymorphisms.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Minkyu
authors.initials: M
authors.lastname: Jung
authors.forename: Ja Seung
authors.initials: JS
authors.lastname: Koo
authors.forename: Young Wha
authors.initials: YW
authors.lastname: Moon
authors.forename: Byeong-Woo
authors.initials: BW
authors.lastname: Park
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Seho
authors.initials: S
authors.lastname: Park
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Soojung
authors.initials: S
authors.lastname: Hong
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Hyun Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Joo Hang
authors.initials: JH
authors.lastname: Kim
authors.forename: Joohyuk
authors.initials: J
authors.lastname: Sohn
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014404:Tubulin; C498585:TUBB3 protein, human; C508053:ERBB2 protein, human