Multidrug Resistance in Breast Cancer: Occurrence and Therapeutic Implications
Abstract
Although clinical development of drug resistance during treatment of breast cancer has been apparent for at least two decades, little is known about the mechanisms involved. Multidrug resistance (mdr) mediated by MDR1 gene expression is one of multiple factors identified which may be associated with declining therapeutic efficacy of anticancer drugs after failure of an initial therapy. This research program evaluated MDRl expression in clinical specimens and demonstrated its lack of a relationship to age, menopausal status, stage, hormone receptors, site of disease, and prior treatment. Through use of clearly defined laboratory methods and specimens from women in defined clinical treatment protocols, MDRl expression was shown to be unrelated to a history of chemotherapy drug treatment in either the neoadjuvant or adjuvant setting. Although MDRl expression was identified in breast tumors using reverse transcriptase PCR techniques, this expression was found to be restricted to lymphoid cells in the breast tumor stroma and was not present in the breast carcinoma cells. As tumor tissue quantity permitted, other molecular alterations were also assessed in the same breast cancer specimens for correlations with responsiveness to treatment. Expression of p53 tumor suppressor gene, HER-2/neu oncogene and an mdr-associated protein, p7, were evaluated. Overexpression of HER-2/neu was correlated with responsiveness to Taxol chemotherapy but expression of p53 was not correlated to responsiveness to Taxol chemotherapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA386630
Entities
People
- Michael Press
Organizations
- University of Southern California