Accession Number : ADA322792

Title :   Multidrug Resistance in Breast Cancer: Occurrence and Therapeutic Implications.

Descriptive Note : Annual rept. 1 Oct 95-30 Sep 96,

Corporate Author : UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES

Personal Author(s) : Muggia, Franco

PDF Url : ADA322792

Report Date : OCT 1996

Pagination or Media Count : 82

Abstract : Drugs that are substrates of MDRI-F-glycoprotein (Pgp) such as doxorubicin and paclitaxel are key components in the current systemic treatment of breast cancer. We have investigated the expression of MDR1 gene and its product, Pgp, in 3 groups of patients with breast cancer. (1) those entered in a clinical trial of paclitaxel for recurrences after chemotherapy (usually containing doxorubicin, 59 patients), (2) patients in a trial of 5-fluorouracil and radiation for locally advanced presentations (17 patients, of whom 14 biopsies were prior to any treatment) and (3) primary cancers within our tissue bank without any prior treatment (39 patients). In 115, expression was determined by immunocytochemistry employing the JSB-I monoclonal antibody (and other Pgp immunostains for comparison). In 35 of these, the findings were confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR). Neither immunohistochemical staining nor RT-PCR demonstrated Pgp expression in any of the breast cancer patients. Because it is unlikely that Pgp is a frequent mechanism of drug resistance for the vast majority of untreated or minimally treated breast cancers, we have shifted our attention towards contrasting the mechanism of MDRI activation in breast versus ovarian cancers and seeking alternate drug-efflux pathways that may be exploited clinically. Within this perspective, our clinical trials have continued to focus on the modulation of paclitaxel activity, its pharmacokinetic consequences, and whether Pgp may be expressed after paclitaxel treatment In the future we plan to explore non-invasive methods such as Technetium-99 sestanibi tumor clearance rates in order to detect reversal of drug-efflux. Such studies should provide important missing information on efflux mechanisms other then Pgp that may be operative in breast cancer.

Descriptors :   *CLINICAL MEDICINE, *NEOPLASMS, *DRUGS, *CHEMOTHERAPY, *RESISTANCE(BIOLOGY), *DRUG TOLERANCE, *BREAST CANCER, PATIENTS, IMMUNOLOGY, MODULATION, PHARMACOLOGY, CYTOCHEMISTRY, OVARIES.

Subject Categories : Medicine and Medical Research
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE