title: Implication of HER-2/neu overexpression for the efficacy of oral fluoropyrimidine-based adjuvant chemotherapy in the patients with estrogen receptor negative breast cancer after surgery.
abstract: BACKGROUND
  The implications of HER-2/neu overexpression for the efficacy of adjuvant chemotherapy (ACT) and endocrine therapy (AET) have been controversial. The present study retrospectively assessed the effects of HER-2/neu overexpression on the efficacy of oral fluoropyrimidine-based ACT and AET after breast cancer surgery.
  
  
  METHODS
  The expression of HER-2/neu protein and estrogen receptor (ER) in 217 primary breast cancers was assessed immunohistochemically using the HercepTest and an anti-ER monoclonal antibody. The overexpression of HER-2/neu was classified into 4 categories (0-3+) according to standard criteria, and 3+ was categorized as HER-2/neu-overexpression. Of the 217 patients, 26 received surgery alone (SA), 32 received ACT, 20 received AET alone and 139 received both AET and ACT. The regimen of the ACT included oral fluoropyrimidines in all patients.
  
  
  RESULTS
  HER-2/neu (3+) overexpression and ER expression were seen in 31.8% (69 out of 217) and 47.5% (103 out of 217) of the patients, respectively. The survival of the HER-2/neu (3+) group was significantly lower than other groups (p = 0.0134), especially in the ER (+) patients (p = 0.0229). However, in the ER (+) patients, HER-2/neu overexpression had no significant effect. The effects of HER-2/neu overexpression and ER expression on the efficacy of the ACT and AET were analyzed by patient survival. In the ER (-) patients, the ACT (+) group had a significantly higher survival rate than the ACT (-) group (p = 0.0459), and this was noted especially in the HER-2/neu-overexpressing cases (p = 0.0485). In the ER (+) patients, ACT and AET did not have any significant influence on the survival regardless of the HER-2/neu status.
  
  
  CONCLUSIONS
  Fluoropyrimidines-based ACT improves the long-term outcome of patients with HER-2/neu-overexpression (3+) and ER (-) breast cancer after surgery.
authors.affiliation: First Department of Surgery, Shimane Medical University, 89-1 Enyacho, Izumo, Shimane 693-8501, Japan. fsurgery@shimane-med.ac.jp
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nio
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itakura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Omori
authors.forename: Makoto
authors.initials: M
authors.lastname: Koike
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Yano
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toga
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higami
mesh_terms: D000284:Administration, Oral; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D012189:Retrospective Studies
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen