Endometrium endometrial cancer

A randomized placebo-controlled trial found that 39% of the tamoxifen-treated women had an endometrial abnormality, a percentage that was reduced to 10% of women on placebo (p < 0.0001) (Kedar et al. 1994), though no cases of endometrial cancer were diagnosed in this study. The histological abnormalities found in the tamoxifen group were atypical hyperplasia (16%), proliferative endometrium (13%), polyps (8%), or presence of mitosis (2%). The authors concluded that the predicative value of an endometrium thickness... 

Tamoxifen is a partial estrogen agonist in breast and thus is used as a treatment and chemopreventative for breast cancer. Tamoxifen is a full agonist in bone and endometrium, and prolonged use of tamoxifen leads to a fourfold to fivefold increase in the incidence of endometrial cancer. See Chapter 56 for a detailed discussion of the use of tamoxifen in breast cancer. 

While the risk that hormone replacement therapy may cause endometrial tumors has been widely discussed, less attention has been given to the possibility that it could increase the risk of epithelial ovarian cancer. Since cancer of the ovary has some risk factors in common with endometrial cancer (notably low parity and obesity), this possible risk needs to be considered, especially in view of the fact that the endometrioid epithelial type of ovarian tumor is histologically so similar to adenocarcinoma of the endometrium. 

The gynecological consequences of antiestrogens (tamoxifen and toremifene) have been evaluated in 167 postmenopausal breast cancer patients in a 3-year prospective study. There was a proliferative endometrium more often in the tamoxifen group than in the toremifene group, but this did not translate into an increase in the rate of endometrial cancer. The authors did not recommend routine surveillance of the endometrium. 

Uterine fibroids and endometrial polyps (sometimes with bleeding) have been reported in menopausal women who had taken tamoxifen for periods of months or years (SEDA-16, 466) (92,93). In view of this, the question of whether tamoxifen increases the risk of endometrial cancer has been widely discussed. The authors of a 1993 review of the outcome of six major trials tended strongly to the conclusion that tamoxifen can cause both endometrial hyperplasia and endometrial cancer proportional to the total dose (94) the figures pointed to an overall incidence of endometrial cancer of 0.5 % in tamoxifen users and 0.1% in controls. Another major review up to 1992 concluded that in the world literature there were 70 cases of uterine malignancies with tamoxifen, including 61 cases of adenocarcinoma of the endometrium and four cases of uterine sarcoma (95). 

Although the endometrial cancers associated with tamoxifen are usually pure adenocarcinomas, other types of rare tumors have also been reported. A pure uterine rhabdomyosarcoma has been reported (99), and a mesodermal mixed tumor of the endometrium occurred 5 years after 5 years of tamoxifen therapy (100). The tumor responded only to combined treatment with doxorubicin, cyclophosphamide, 5-fluorouracil, and carbopla-tin. It is possible that this type of tumor arises later than adenocarcinomas and should be looked for during longterm use of tamoxifen. 

Carcinoma of the endometrium is associated only with unopposed oestrogens, which increase risk by 2-fold during 5 years rising to 7-fold with longer treatment. Because endometrial cancer is uncommon, the absolute risk is about one-tenth that of thromboembolic disease the risk reduces over 5-10 years after stopping treatment. 

Also, lower doses of estrogen may be associated with a lower risk of endometrial hyperplasia. Raloxifene does not resnlt in endometrial hyperplasia, has no effect on endometrial thickness, is not associated with polyp formation, and has virtnally no proliferative effect on the endometrium. A 4-year trial of raloxifene in women with osteoporosis showed no increased risk of endometrial cancer." ... 

Progression to malignancy in breast and endometrium is often accompanied by disrupted expression of PR-A and PR-B [111, 112]. Development of PR agonists and antagonists selective to the PR-A and PR-B isoforms may prove to be of great clinical benefit in breast and endometrial cancer. Selective PR-A agonists are currently in development [113, 114]. 

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