Concentrations of tamoxifen and its major metabolites in hormone responsive and resistant breast tumours

Patients treated with tamoxifen (TAM) for primary breast cancer often manif est de novo or acquired resistance, possibly through changes in drug metabo lism. Using solid-phase extraction methods and reversed-phase high-performa nce liquid chromatography separations, levels of TAM and metabolites 4-hydr oxytamoxifen (4OH) and desmethyltamoxifen (DMT) have been measured in plasm a and tumour tissue from breast cancer patients treated with TAM for at lea st 3 months. Patients were categorized into those with tumours responding t o TAM and those showing de novo or acquired resistance. Levels of TAM, 4OH and DMT in both plasma and tissue samples were correlated with clinical res ponse, length of treatment and patient weight. Interesting results included accumulation of 4OH in tumour tissues over time in all patients, with sign ificance reached in the acquired resistance group. In addition, significant ly lower levels of 4OH and DMT were found in plasma taken from responding p atients after 3 months of treatment when compared to non-responding patient s. and a small group of ER-poor patients showed significantly lower levels of all three species in plasma when compared to other patients. Whilst not explaining TAM resistance in all cases, these differences could account for the development of resistance to TAM treatment in certain subgroups of pat ients. (C) 2000 Cancer Research Campaign.