Serum HER‐2/neu conversion to positive at the time of disease progression in patients with breast carcinoma on hormone therapy
Open Access
- 10 June 2005
- Vol. 104 (2), 257-263
- https://doi.org/10.1002/cncr.21202
Abstract
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. Cancer 2005. © 2005 American Cancer Society.Keywords
This publication has 18 references indexed in Scilit:
- Serum HER-2/neu and Response to the Aromatase Inhibitor Letrozole Versus TamoxifenJournal of Clinical Oncology, 2003
- Elevated Levels of Epidermal Growth Factor Receptor/c-erbB2 Heterodimers Mediate an Autocrine Growth Regulatory Pathway in Tamoxifen-Resistant MCF-7 CellsEndocrinology, 2003
- The Emerging Role of Monitoring Serum HER-2/neuOncoprotein Levels in Women with Metastatic Breast CancerLaboratory Medicine, 2003
- Constitutive MEK/MAPK Activation Leads to p27Kip1Deregulation and Antiestrogen Resistance in Human Breast Cancer CellsPublished by Elsevier ,2001
- Oestrogen and growth factor cross-talk and endocrine insensitivity and acquired resistance in breast cancerBritish Journal of Cancer, 2000
- Involvement of steroid hormone and growth factor cross-talk in endocrine response in breast cancer.Endocrine-Related Cancer, 1999
- Constitutive Raf-1 kinase activity in breast cancer cells induces both estrogen-independent growth and apoptosisOncogene, 1997
- Oestrogen receptor: a stable phenotype in breast cancerBritish Journal of Cancer, 1996
- Measurement of steroid hormone receptors in breast cancer patients on tamoxifenBreast Cancer Research and Treatment, 1993
- Changes in epidermal growth factor receptor expression and response to ligand associated with acquired tamoxifen resistance or oestrogen independence in the ZR-75-1 human breast cancer cell lineBritish Journal of Cancer, 1992