title: Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer.
abstract: OBJECTIVE
  To determine the effect of elevation of serum HER-2/neu on response to hormone therapy.
  
  
  METHODS
  Seven hundred nineteen metastatic patients with estrogen receptor-positive (ER(+)), progesterone receptor-positive, or both or ER status unknown breast cancer were randomized in three independent clinical trials to receive second-line hormone therapy with either megestrol acetate or an aromatase inhibitor (fadrozole or letrozole). An automated enzyme-linked immunosorbent assay specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to detect serum levels.
  
  
  RESULTS
  Two hundred nineteen patients (30%) had elevated serum HER-2/neu protein levels, using the mean + 2 SD (15 ng/mL) from the serum of healthy women as an upper limit. Response to treatment was available for 711 patients. The response rate (complete responses plus partial responses plus stable disease) to endocrine therapy was 45% in 494 patients with non-elevated and 23% in 217 patients with elevated serum HER-2/neu levels (P <.0001). Median duration of treatment response (using the time to progression [TTP] variable for patients who responded) was shorter in the group with elevated serum HER-2/neu levels (11.7 months) compared with the patient group with non-elevated levels (17.4 months). TTP, time to treatment failure, and median survival (17.2 months v 29.6 months) were also significantly shorter in the patients with elevated serum HER-2/neu levels (P <.0001).
  
  
  CONCLUSIONS
  Patients with ER(+) and serum HER-2/neu-positive metastatic breast cancer are less likely to respond to hormone treatment and have a shorter duration of response than ER(+) and serum HER-2/neu-negative patients. Their survival duration is also shorter.
authors.affiliation: Department of Hematology and Oncology, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA. alipton@psu.edu
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: S M
authors.initials: SM
authors.lastname: Ali
authors.forename: K
authors.initials: K
authors.lastname: Leitzel
authors.forename: L
authors.initials: L
authors.lastname: Demers
authors.forename: V
authors.initials: V
authors.lastname: Chinchilli
authors.forename: L
authors.initials: L
authors.lastname: Engle
authors.forename: Harold A
authors.initials: HA
authors.lastname: Harvey
authors.forename: C
authors.initials: C
authors.lastname: Brady
authors.forename: C M
authors.initials: CM
authors.lastname: Nalin
authors.forename: M
authors.initials: M
authors.lastname: Dugan
authors.forename: W
authors.initials: W
authors.lastname: Carney
authors.forename: J
authors.initials: J
authors.lastname: Allard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D016009:Chi-Square Distribution; D018450:Disease Progression; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018719:Erb-b2 Receptor Tyrosine Kinases