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 recurrent breast cancer. Serum tamoxifen was similar in patients with acquired and de-novo resistance, but intra-tumoral concentrations were significantly lower in patients with acquired resistance. Tumour oestrogen-receptor concentrations at relapse did not support the hypothesis that selective outgrowth of oestrogen-receptor-negative cells is a major mechanism for acquired tamoxifen resistance. Reduced intra-tumoral tamoxifen levels during prolonged therapy may be an important mechanism for acquired resistance in breast cancer.