APPEARANCE AND DETECTION OF MULTIPLE COPIES OF THE MDR-1 GENE IN CLINICAL-SAMPLES OF MAMMARY-CARCINOMA

To examine the presence of multiple copies of the mdr-1 gene in clinical tumor samples we have developed an approach where the cells are obtained by fine-needle biopsies and the number of gene copies determined by PCR. The temporal appearance of amplified mdr-1 was examined in 20 breast-cancer patients with clinical stage-IV disease receiving endocrine treatment. Tumor samples were obtained every 2nd to 3rd month from the same tumor lesion. None of the initial samples from each patient contained multiple copies of mdr-1. Of 16 patients who showed increased tumor size, 4 developed multiple gene copies, showing that the event occurs without cytotoxic selection of cells with chemotherapy.