Endometrial polyps tamoxifen

The estrogenicity of tamoxifen at several levels brings both advantages and inconveniences. Among the former we have already mentioned bone quality and vaginal proliferation. However, the inconveniences, especially endometrial polyps and cancer and thrombotic events, are important enough to avoid the... 

A Japanese study of DNA extracted from endometrial polyps in women treated with tamoxifen showed a threefold increase in K-ras mutations compared with the incidence in cases of spontaneous endometrial hyperplasia. These findings could support the hypothesis that the endometrial polyps will prove an early indicator for the development of endometrial carcinoma in such patients (86). 

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). 

When assessing the risk of endometrial malignancy in women with breast cancer taking tamoxifen, it is worth taking into account evidence that patients with breast cancer may at the outset have some endometrial pathology. In women with breast cancer scheduled for tamoxifen there were endometrial polyps in 9.3%, endometrial cysts in 16%, and synechiae in 12% at the outset. Tamoxifen significantly increased the incidence of these benign endometrial lesions, usually after less than 1 year of treatment. There were no cases of endometrial carcinoma in 34 patients who had taken tamoxifen for 12-24 months, and only one in 78 patients who had taken it for 5-72 months (103). 

Cohen I, Azaria R, Bernheim J, Shapira J, Beyth Y. Risk factors of endometrial polyps resected from postmenopausal patients with breast carcinoma treated with tamoxifen. Cancer 2001 92(5) 1151-5. 

Cohen I, Bernheim J, Azaria R, Tepper R, Sharony R, Beyth Y. Malignant endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients. Gynecol Oncol 1999 75(1) 136-41. 

Biron-Shental T, Tepper R, Fishman A, Shapira J, Cohen I. Recurrent endometrial polyps in postmenopausal breast cancer patients on tamoxifen. Gynecol Oncol 2003 90 382-6. 

Hachisuga T, Miyakawa T, Tsujioka H, Horiuchi S, Emoto M, Kawarabayashi T. K-ras mutation in tamoxifen-related endometrial polyps. Cancer 2003 98 1890-7. 

Houghton JP, Ioffe OB, Silverberg SG, McGrady B, McCluggage WG. Metastatic breast lobular carcinoma involving tamoxifen-associated endometrial polyps report of two cases and review of tamoxifen-associated polypoid uterine lesions. Mod Pathol 2003 16 395-8. 

Nuovo MA, Nuovo GJ, McCaffrey RM, Levine RU, Barron B, Winkler B. Endometrial polyps in postmenopausal patients receiving tamoxifen. Int J Gynecol Pathol 1989 8(2) 125—31. 

In fact, the most widely recognized adverse effects of tamoxifen are those related to the stimulatory effects on the endometrium. These effects include proliferation of the endometrium (Dijkhuizen et al., 1996 Hann et al., 1997 Lahti et al., 1993), formation of endometrial polyps (Cohen et al., 1997 Hann et al., 1997 Kedar et al., 1994a Lahti et al., 1993), hyperplasia (Cohen, 1997 Lahti et al, 1993), and cancer (Fisher et al, 1994 Rutqvist et al., 1995 Stearns and Gelmann, 1998 Wilking et al, 1997). Other reproductive side effects of tamoxifen are worsening of endometriosis (Buckley, 1990 Hajjar et al, 1993 Ismail and Maulik, 1997), adenomyosis (Cohen etal, 1997), and proliferation of benign uterine tumors (Cohen, 1997 Kang et al, 1996). 

Tamoxifen can be associated with the formation of endometrial polyps and polypoid endometriosis these polyps ( basilomas ) can become malignant (55,56), perhaps because they lack progesterone receptors and are exposed to unopposed estrogen (57). 

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) (62,63). In view of this, the question of whether tamoxifen increases the risk of... 

Tanioxircn hits seen extensive use in treating primary breast cancers that arc ER dependent, For premenopausal women with metastatic disease, tamoxifen is an alternative and adjuvant with oophorectomy, ovarian irradiation, and mastectomy. Tamoxifen u.se. however, is not problem free. Tamoxifen increases the incidence of endometrial polyps. hyperplasia, and carcinoma and uterine sarcomas. The risk of endometrial cancer resulting from tamoxifen is. however. much lower than the "modest but highly significant reductions in morbidity and mortality of breast cancer." Becau.se of the increased risk of endometrial cancer with tamoxifen therapy, tamoxifen. should be u.sed to prevent breast cancer only in women at high ri.sk. Women without a family history of breast cancer or other risks should not use tamoxifen in this manner. 

Reproductive system Endometrial polyps during tamoxifen treatment can be prevented by the simultaneous use of intrauterine levonorgestrel (the Mirena system), but the method is of limited usefiil-ness, since its effects lasts only as long as the Mirena is in place once it is removed, and while tamoxifen is continued, the polyps recur [57 ]. There are differing opinions on this form of administration (see the special review below). 

Gardner FJ, Konje JC, Bell SC, Abrams KR, Brown LJ, Taylor DJ, Habiba M. Prevention of tamoxifen induced endometrial polyps using a levo-norgestrel releasing intrauterine system long-term follow-up of a randomised control trial. Gynecol Oncol 2009 114(3) 452-6. 

The presence of an enlarged endometrium (> 5 mm) may be associated with endometrial abnormalities, principally polyps, hyperplasia, or even adenocarcinoma of the endometrium, in the postmenopausal woman (Dijkhuizen et al. 1996 Granberg et al. 1991 Holbert 1997). It seems that treatment with tamoxifen in postmenopausal women sustains this association. Thus, in the previously mentioned study by Cohen et al. (1994), the only endometrial abnormalities were found in those women whose endometrium had a thickness... 

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... 

In a prospective study in 77 consecutive women with postmenopausal breast cancer scheduled to start endocrine treatment for breast cancer, using either tamoxifen or an aromatase inhibitor tamoxifen treatment significantly increased endometrial thickness and uterine volume after 3 months (24). In additional, tamoxifen induced endometrial cysts and polyps and increased the size of pre-existing fibroids. In contrast, aromatase inhibitors did not stimulate endometrial growth and were not associated with endometrial pathology. Furthermore, they reduced endometrial thickness and uterine volume in patients who had previously taken tamoxifen. 

Ramondetta LM, Sherwood JB, Dunton CJ, Palazzo JP. Endometrial cancer in polyps associated with tamoxifen use. Am J Obstet Gynecol 1999 180(2 Pt 1) 340—1. 

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