Development of Anti-Idiotype Monoclonal Antibodies for the Treatment of Breast Cancer.
Abstract
Breast cancer is a major cause of cancer deaths in women. The incidence of breast cancer has steadily increased over the last two decades and patients with recurrent disease are not curable by standard therapies. In human breast cancer,amplification and overexpression of the cell membrane protein HER2/neu, which is not present on normal breast tissue, has been observed to occur in a significant number of tumors. In 189 primary human breast cancers, HER2/neu was found to be amplified from 2 to over 20 fold in 30% of the tumors (1) Patients with multiple copies of the HER2/neu gene in DNA from their tumors had a shorter time to relapse as well as a shorter overall survival (1-3), indicating that HEK2/neu gene amplification was prognostic for both disease behavior and clinical outcome in these patients. Not only were increased copy numbers of HER2/neu in breast cancers related to a poorer prognosis, but gene amplification of HER2/neu correlated with lymph node involvement (1- 5), histological grade (5,6), negative estrogen receptor content (7,8), early recurrence (4,7), increased mitotic activity (9), all of which are considered to be poor prognostic indicators. In a retrospective study, the expression of HEK2/neu determined immunohistochemically in positive breast cancer samples from 253 patients found that HER2/neu positive breast cancers behaved more aggressively in the first 2-3 years following diagnosis (10) Several studies have shown that overexpression of HEK2/neu occurs in as many as 15-40% of breast cancers and that overexpression of HEK2/neu is associated with poor survival (1-3). Therefore 11ER2/neu present on the surface of overexpressing breast cancer cells offers a good target for immunotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 15, 1995
- Accession Number
- ADA296100
Entities
People
- Amanda Sherratt
- Malaya Chatterjee
Organizations
- University of Kentucky