Overview from the International Conference on Long-Term Tamoxifen Therapy for Breast Cancer.

The development of tamoxifen therapy to treat selected patients, with all stages of breast cancer, has provided the clinical community with an efficacious and safe drug for long-term therapy. Issues of safety are under constant review, but justified concerns about high doses of tamoxifen acting as a promoter of liver cancer in rats or as a promoter of endometrial cancer in women have not, as yet, proved to be of clinical relevance. The situation will continue to be reviewed during the development of the prevention studies in Europe and the United States because an improvement in women's health is the ultimate goal of these programs.

A molecular strategy to control tamoxifen resistant breast cancer.

Our research goal is to develop possible strategies that could have therapeutic implications for the control of breast cancer. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for the majority, who have ER negative disease. There is also both laboratory and clinical evidence to support the position that initially responsive tumours will eventually develop resistance to tamoxifen therapy.

The importance of steroid hormones in prostate cancer.

Steroid hormones have an important role in prostate biology. Androgens are crucial for the normal development of the prostate gland and in maintaining its functional state in the adult. It seems that the prolonged presence of androgens might also be an important factor in the development of prostate cancer.

Tamoxifen in axillary node--negative breast cancer: multisystem benefits and risks.

Adjuvant tamoxifen therapy is associated with modest improvement in disease-free and overall survival in women with invasive axillary node-negative breast cancer. The preponderance of data supporting these general conclusions are from trials in postmenopausal women; in premenopausal women data appear convincing regarding disease-free, but not overall, survival. Firm conclusions regarding magnitude of benefit related to presence of different prognostic factors cannot be drawn at present.

Comparison of acyltransferase-mediated mutagenicity and nucleic acid binding of N-acetoxy-4-acetylaminobiphenyl by hepatic and bladder microsomes from rats and dogs.

Acyltransferase-mediated mutagenic and metabolic activation of N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) by hepatic tissues of rats and dogs were compared. N-OAc-AABP was mutagenic in Salmonella typhimurium TA98 even in the absence of exogenous enzyme(s). However, supplementation with hepatic microsomes from dogs showed a dose-dependent increase in mutagenicity of N-OAc-AABP, whereas under the same conditions, rat microsomes were inactive.

Reversible control of oestradiol-stimulated growth of MCF-7 tumours by tamoxifen in the athymic mouse.

We investigated the ability of high concentrations of oestradiol to reverse the growth inhibitory action of tamoxifen on MCF-7 breast cancer cells in vivo. Tamoxifen inhibits the oestradiol stimulated growth of MCF-7 cells in athymic mice. Using a sustained release preparation of tamoxifen we consistently achieved serum concentrations of the drug in the 40 to 50 ng ml-1 range and much higher levels in tissues.

Alteration of endocrine parameters in premenopausal women with breast cancer during long-term adjuvant therapy with tamoxifen as the single agent.

Tamoxifen is used to treat selected patients at each stage of breast cancer. Although most clinical experience has been obtained with postmenopausal women, increasing numbers of premenopausal women will be treated with 5 or more years of adjuvant tamoxifen therapy following surgery. Indeed, the proposed use of tamoxifen to prevent breast cancer in high-risk women could result in its extended use during the childbearing years.