Management of Advanced Breast Cancer: Defining the Role of Toremifene
Stephen M. Holliday
Breast cancer is an important cause of morbidity and mortality in women. Although many risk factors are thought to influence the development of breast cancer, the most important of these are a family history of disease and reproductive and endocrine factors. The incidence of breast cancer is increasing in both developed and developing countries. However, earlier detection and improvements in treatment have resulted in a stabilisation of mortality rates in developed countries. Early detection is associated with decreased breast cancer mortality. Advanced breast cancer, however, is generally considered incurable. As such, the aim of pharmacotherapy for women with advanced disease is palliation of symptoms while minimising drug toxicity. In women with asymptomatic metastatic disease that is not rapidly progressive, hormone therapy is the treatment of first choice because of its better tolerability profile compared with most cytotoxic chemotherapy regimens. Antiestrogens are preferred as first-line hormone therapy because they are generally better tolerated than other hormone drugs such as aromatase inhibitors and progestins. Localised treatment also has a role in disease palliation. Surgery, as an adjunct to chemotherapy, can facilitate disease control, and irradiation is beneficial in patients with painful bone or CNS metastases. Toremifene is the first antiestrogen to be approved for the treatment of advanced breast cancer since tamoxifen became available about 20 years ago. Comparative clinical trials have demonstrated that toremifene has similar efficacy and tolerability to that of tamoxifen in postmenopausal patients with tumours of positive or unknown hormone receptor status and who do not have rapidly progressive disease. Like tamoxifen, toremifene also demonstrates partial estrogenic activity, producing beneficial effects on bone metabolism and the blood lipid profile. Tamoxifen, however, has been associated with an increased risk of endometrial cancer, and preclinical data suggest that toremifene has a lower carcinogenic potential than tamoxifen. In summary, the apparent lower carcinogenic potential of toremifene versus tamoxifen requires confirmation in clinical trials, but the overall clinical relevance of such a benefit in the setting of advanced disease is unclear. Toremifene, however, is an equally effective and well tolerated alternative to tamoxifen for primary hormone treatment of postmenopausal women with advanced breast cancer.
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