ACQUIRED TAMOXIFEN RESISTANCE IN HUMAN BREAST-CANCER AND REDUCED INTRA-TUMORAL DRUG CONCENTRATION

Reduced intra-tumoral drug concentrations have been investigated as a mechanism of tamoxifen resistance in 51 patients with locally recurren t breast cancer. Serum tamoxifen was similar in patients with acquired and de-novo resistance, but intra-tumoral concentrations were signifi cantly lower in patients with acquired resistance. Tumour oestrogen-re ceptor concentrations at relapse did not support the hypothesis that s elective outgrowth of oestrogen-receptor-negative cells is a major mec hanism for acquired tamoxifen resistance. Reduced intra-tumoral tamoxi fen levels during prolonged therapy may be an important mechanism for acquired resistance in breast cancer.