Gynecologic effects of tamoxifen and the association with endometrial carcinoma

Abstract

Tamoxifen has been used as an adjuvant therapy for breast cancer for nearly two decades. The benefits of adjuvant tamoxifen therapy in prolonging disease-free and overall survival have been shown in randomized clinical trials. Despite this, some developing evidence suggests that tamoxifen causes a 2- to 3-fold increase in endometrial cancer. This paper reviews the reports of endometrial carcinoma in tamoxifen-treated patients. Two hundred fifty cases of endometrial carcinoma are reported, but only one case is identified in a premenopausal woman. When documented, 77% (n=127) of the cases are good-grade (grade 1 or 2) and 80% (n=125) are stage-I disease. Since the distribution of good grade (79%) and stage I (74%) from the Surveillance, Epidemiology and End Results (SEER) data are comparable, concerns about more aggressive or late-stage disease appear to be unwarranted. The modest increase in the incidence of early-stage, good-grade endometrial carcinoma described during tamoxifen therapy suggests that it would be unreasonable to institute an aggressive detection strategy of endometrial biopsies. This approach would only lead to further detection bias and would not be cost-effective. Physicians should ensure that patients do not have pre-existing endometrial cancer prior to adjuvant tamoxifen therapy for breast cancer and, furthermore, they should educate patients about signs and symptoms of early endometrial carcinoma and when reported these should be followed up with a gynecologic examination.

Responsiveness of endometrial genes Connexin26, Connexin43, C3 and clusterin to primary estrogen, selective estrogen receptor modulators, phyto- and xenoestrogens

“…The synthetic estrogen, tamoxifen, which is widely used as an antiestrogen in the treatment of breast cancer (Nass et al 1998, Overmoyer 1999) reveals agonistic effects in the uterus which lead to an increased risk of development of endometrial cancer after long-term tamoxifen therapy (Assikis & Jordan 1995, Sato et al 1996, Carmichael 1998). We confirmed this agonistic effect on the endometrium by its influence on transcriptional regulation of Cx26, C3 and clusterin gene expression.…”

Prevention of N-Methyl-N-Nitrosourea–Induced Breast Cancer by α-Fetoprotein (AFP)–Derived Peptide, a Peptide Derived from the Active Site of AFP

“…Tamoxifen, currently used as a hormonal therapeutic for estrogen receptor -positive breast cancer (2), has also been used effectively as a chemopreventive agent in patients at high risk for acquiring breast cancer (3). However, tamoxifen may be accompanied by significant host toxicity (4,5). For example, women taking tamoxifen have more than twice the chance of developing uterine cancer as do women taking placebo (4,5).…”

“…However, tamoxifen may be accompanied by significant host toxicity (4,5). For example, women taking tamoxifen have more than twice the chance of developing uterine cancer as do women taking placebo (4,5). Cardiovascular side effects of tamoxifen, including thromboembolism (5), have been reported.…”

Estrogenic Effects of a Kampo Formula, <i>Tokishakuyakusan</i>, in Parous Ovariectomized Rats

“…However, tamoxifen is associated with a low incidence of serious side effects due to its partial estrogen agonistic effect in the human uterus. 42) The National Surgical Adjuvant Breast and Bowel Project-P1 Study showed that tamoxifen does not increase the risk of endometrial carcinogenesis 3-to 4-fold in postmenopausal, compared with pre-menopausal women. Furthermore, the rate of endometrial carcinogenesis in postmenopausal women is the same as that in the general population.…”