title: Clinical usefulness of human epidermal growth factor receptor-2 extracellular domain as a biomarker for monitoring cancer status and predicting the therapeutic efficacy in breast cancer.
abstract: We assessed the clinical usefulness of human epidermal growth factor receptor-2 extracellular domain (HER2ECD) as a biomarker for detecting cancer and monitoring disease status and for predicting the efficacy of anticancer treatment in breast cancer. Five-hundred and eighty serum samples from 252 patients with breast cancer were examined for the concentration of HER2ECD to compare with conventional tumor markers (CEA, CA15-3, NCC-ST439 and BCA225). Also, in 19 patients with HER2-overexpressed advanced or recurrent breast cancer who were treated with trastuzumab, clinical outcomes were evaluated retrospectively to determine whether their serum HER2ECD levels predict clinical responses. The proportion of patients with elevated HER2ECD levels was 15.1%, which was compatible with those with elevated conventional marker levels. In patients with HER2-overexpressed breast cancer, the positive rate of HER2ECD was significantly higher (24.1%) than those of conventional markers (7.4-12.9%), suggesting the usefulness of HER2ECD for detecting cancer in this population. HER2-overexpressed patients responding to trastuzumab (12 of 19 patients) showed significantly higher serum HER2ECD level (p = 0.033) and longer time to progression (TTP) (p = 0.039) and overall survival (OS) (p = 0.031) than did patients not responding (seven patients). Furthermore, higher response rates were observed in patients with elevated HER2ECD levels than in patients without elevated HER2ECD levels (91.3% vs. 14.3%, p = 0.032), whereas there was no difference in survival between the two groups. The results suggest that HER2ECD is a useful biomarker not only for detecting breast cancer recurrence but also for predicting tumor responses to trastuzumab.
authors.affiliation: Department of Respiratory, Breast and Endocrine Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan. konbat@med.kagawa-u.ac.jp
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kontani
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kuroda
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Chisa
authors.initials: C
authors.lastname: Murazawa
authors.forename: Shoko
authors.initials: S
authors.lastname: Norimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohtani
authors.forename: Naomi
authors.initials: N
authors.lastname: Fujiwara-Honjo
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kushida
authors.forename: Manabu
authors.initials: M
authors.lastname: Date
authors.forename: Reiji
authors.initials: R
authors.lastname: Haba
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Houchi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yokomise
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000737:chemistry; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D018270:Carcinoma, Ductal, Breast / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000068878:Trastuzumab; C508053:ERBB2 protein, human