Serum HER-2/neu conversion to positive at the time of disease progression in patients with breast carcinoma on hormone therapy.
BACKGROUND
Prolonged exposure of breast carcinoma cells in vitro to tamoxifen results in tamoxifen resistance. Tamoxifen-resistant cells express increased HER-2/neu mRNA and protein. The objective of this study was to determine whether patients with metastatic or locally advanced breast carcinoma who have negative serum HER-2/neu status at the initiation of first-line hormone therapy with letrozole or tamoxifen convert to positive serum HER-2/neu status at the time of disease progression and to determine whether serum HER-2/neu conversion to positive status is associated with response to therapy and overall survival.


METHODS
Serum samples were obtained at baseline and at the time of disease progression from 240 patients who initially had negative serum HER-2/neu status (< 15 ng/mL). A manual microtiter, enzyme-linked immunosorbent assay that was specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein product was used to quantitate serum levels.


RESULTS
Among 240 patients, 61 patients (26%) converted from serum HER-2/neu negative to positive (> 15 ng/mL) at the time of disease progression. Thirty-two of 129 patients (25%) who were treated with tamoxifen and 29 of 111 patients (26%) who were treated with letrozole became converted to positive serum HER-2/neu status at the time of disease progression. The response rate and the time to disease progression on first-line hormone therapy were not affected by serum HER-2/neu conversion. The survival of patients who converted to positive serum HER-2/neu status was significantly shorter compared with the survival of patients who remained negative for serum HER-2/neu. A multivariate analysis revealed that conversion to positive serum HER-2/neu status was an independent prognostic variable for survival.


CONCLUSIONS
Conversion to positive serum HER-2/neu status occurred in approximately 25% of patients who received first-line hormone therapy. Conversion to serum HER-2/neu-positive status occurred with equal frequency in antiestrogen and aromatase-inhibitor therapy. The current results showed that serum conversion to HER-2/neu-positive status was an independent risk factor for decreased survival in patients with breast carcinoma.
Lipton
Allan
A
Department of Hematology/Oncology, Hershey Medical Center, Penn State University, Hershey, Pennsylvania 17033, USA. alipton@psu.edu
Leitzel
Kim
K
Ali
Suhail M
SM
Demers
Laurence
L
Harvey
Harold A
HA
Chaudri-Ross
Hilary A
HA
Evans
Dean
D
Lang
Raquel
R
Hackl
Wolfgang
W
Hamer
Peter
P
Carney
Walter
W
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D018450:Disease Progression; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles