Tamoxifen long-term effects

Cozick J, Allen D, Baum M, et al. (1992) Long term effects of Tamoxifen biological effects of Tamoxifen working party. Eur J Cancer 29 15-21... 

Kesim MD, Aydin Y, Atis A, Mandiraci G. Long-term effects of the levonorgestrel-releasing intrauterine system on serum lipids and the endometrium in breast cancer patients taking tamoxifen. Climacteric 2008 11 252-7. 

Jordan VC, Fritz NF, Tormey DC (1987a) Long-term adjuvant therapy with tamoxifen effects on sex hormone binding globulin and antithrombin III. Cancer Res 47 4517-4519... 

Wright CDP, Mansell RE, Gazet JC, et al. (1993) Effect of long term Tamoxifen treatment on bone turnover in women with breast cancer. Br Med J 306 429-430... 

Alternatives to steroid hormone therapy for osteoporosis include raloxifene, bisphosphonates, sodium fluoride, vitamin D and calcium supplementation, calcitonin, and parathyroid hormone. Tamoxifen has estrogenic effects on bone and delays bone loss in postmenopausal women. However as a result of estrogenic activity in the uterus, long-term tamoxifen administration has been associated with an increased risk of... 

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists Group. Comprehensive side effect profile of anastrozole and tamoxifen as adjuvant treatment for early stage breast cancer long term safety analysis of the ATAC trial. Lancet Oncol 2006 7 633 13. 

Gerber B, Krause A, Muller H, Reimer T, Kulz T, Makovitzky J, Kundt G, Friese K. Effects of adjuvant tamoxifen on the endometrium in postmenopausal women with breast cancer a prospective long-term study using transvaginal ultrasound. J Clin Oncol 2000 18(20) 3464—70. 

In addition to its limited duration of beneficial effects in breast cancer, a serious problem associated with tamoxifen is its stimulatory effect on the endometrium, leading to endometrial hyperplasia and even cancer (Fisher etal., 1996 Kedar etal., 1994 Robinson etal., 1995). We thus have the example of a compound for which the benefits exerted on breast cancer and bone are accompanied by adverse effects in another tissue. In fact, as mentioned above, even the beneficial effects observed in breast cancer deserve some important comments because of the limit of 5 years of treatment, which raises practical questions about the use of this compound for prevention of breast cancer (Fisher et al., 1996) while, in fact, long-term use is required. Analogues of tamoxifen have... 

Journal of Medicine, was compared with placebo in postmenopausal breast cancer patients who had completed 5 years of tamoxifen therapy. After a median follow-up of 2.4 years, letrozole was associated with superior estimated 4-year DFS compared with placebo in this setting (93% vs. 87% p <0.001). While these results were preliminary, patients were unblinded and allowed to crossover to the active arm of therapy. Therefore effects on survival will never be ascertained. However, further follow-up will be completed with regard to safety and DFS in those patients randomized to letrozole from the beginning of the trial. Based on the results of this study, letrozole received FDA approval in November 2004 for extended adjuvant therapy (i.e., after 5 years of tamoxifen therapy). In another recent trial, patients who had completed 2 to 3 years of adjuvant tamoxifen therapy were randomized to continue tamoxifen or crossover to exemestane for the remainder of the 5 years. After a median followup of 30.6 months, DFS was substantially longer with exemestane compared with continuation of tamoxifen (91.5% vs. 86.8% HR = 0.68,p = 0.00005). Concerns regarding long-term safety also arise with this study, with data indicating a possible increase in cardiovascular disease, osteoporosis, and visual disturbances with exemestane compared with tamoxifen. 

---