Effects of Tamoxifen on Cardiovascular Risk Factors in Postmenopausal Women After 5 Years of Treatment

Abstract

BACKGROUND: Adjuvant tamoxifen therapy for breast cancer has been given for a period of several years. Cardiovascular diseases increased in incidence rapidly in women older than 60 years. Favorable changes in cardiovascular risk factors have been seen with 2 years of tamoxifen therapy, and lower rates of myocardial infarction and of hospitalization for heart disease have been observed in tamoxifen-treated women. PURPOSE: We sought to evaluate changes in risk factors for cardiovascular diseases in postmenopausal women after therapy with tamoxifen for 5 years. METHODS: Five years after their initial entry in a 2-year randomized, placebo-controlled toxicity study, we re-examined 62 of the original 140 disease-free, axillary node-negative postmenopausal breast cancer patients. These 62 patients were women available for study because they had not suffered major illness and had continued on either the tamoxifen or no-tamoxifen regimen to which they had been originally randomly assigned for the entire 5 years. Patient and control blood samples were analyzed for total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and subfractions, triglycerides, apolipoprotein AI, apolipoprotein B, lipoprotein(a), fibrinogen, glucose, and platelets. RESULTS: At base line for all measurements except atherogenic lipoprotein [lipoprotein(a)], the 30 long-term tamoxifen recipients and the 32 long-term no-tamoxifen recipients were not significantly different. After 5 years, levels of total serum cholesterol (P < .001), LDL cholesterol (P < .001), and lipoprotein(a) (P = .001) were significantly lower, and apolipoprotein AI levels were significantly higher (P < .001) in the tamoxifen-treated group compared with the no-tamoxifen group. Apolipoprotein B levels increased to a greater extent in the no-tamoxifen than in the tamoxifen group (P < .001). After 5 years, fibrinogen level decrease and triglyceride level increases in the tamoxifen group compared with the no-tamoxifen group were of borderline statistical significance and HDL cholesterol levels were not different in the two groups. CONCLUSION: Favorable changes in lipid, lipoprotein, and fibrinogen levels seen early in tamoxifen therapy in postmenopausal women persist with treatment of 5 years. IMPLICATIONS: The types and magnitude of changes in cardiovascular risk factors seen here with tamoxifen are similar to a certain extent with those seen with estrogen supplements. Further risk-factor and ethnic-group data are needed to estimate the magnitude of expected benefits of tamoxifen treatment on incidence of heart disease.