
Estrogen look-alikes [agonists] like tamoxifen compete with estrogen for binding to estrogen receptors.  They can block tumor growth stimulated by estrogen. This seems to work very well with breast cancer cells that are ER+. 

However, with uterine tissue, the tamoxifen-receptor complex can stimulate the uterine endometrium and promote uterine endometrial tumor growth. Tamoxifen therapy has been shown to result in an increased incidence of endometrial cancers and other endometrial growths in women. It acts as a stimulator of the uterus. It has been implicated in the appearance of leiomyosarcomas in women being treated with it. It is not recommended for use of people with endometrial tumors, because it can stimulate uterine endometrial growth. It can stimulate growth of uterine LMS tumors and their metastases.

Jim wrote:
"My wife was diagnosed with LMS after hysterectomy for a fibroid 2 years ago, common story on the list, so I thought I'd share what we learnt from Dr Judson at the Royal Marsden (London)." He continued: "First a bit more history. Local mets were detected 1 year ago; she had 6 courses of Adriamycin that resulted in some shrinkage. 5 weeks ago she had abdominal surgery--several tumours were removed. Unfortunately the surgeon saw a lot more small suspicious patches which he couldn't remove." " Dr Judson suggested anti-hormone therapy - even though the receptor assays were not back yet. He suggested letrozole, which is an aromatase inhibitor [i.e. it effectively blocks oestrogen production], rather than Tamoxifen, which interferes with the binding of oestrogen on the cells. The reason he gave was that while Tamoxifen has anti-oestrogen activity in Breast cancer it has been shown to act as an oestrogen in some cases including Uterine Endometrium. It is therefore possible (? probable?) that Tamoxifen might actually stimulate Uterine LMS." "I've thought about this since - it seems strange that the same drug can have two opposite effects - it appears that it is down to the cell receptors. It may bind but not be a good enough fit to trigger the action (i.e. Breast cancer cells) while slightly different receptors will be triggered. Anyway Maureen is trying Letrozole for 3 months and then having a scan and review. Hope this might help in that it may give you another option to discuss."
The best information available about the serious side effects of tamoxifen comes from 30 years of clinical trials, including the BCPT. In the BCPT, women taking tamoxifen had more than twice the chance of developing endometrial cancer (cancer of the lining of the uterus or womb) compared with women who took the placebo (36 of the 6,600 women taking tamoxifen versus 15 of the 6,600 women taking placebo). The risk was higher in women over the age of 50. The increased risk is in the same range as the risk for postmenopausal women taking single-agent estrogen replacement therapy. Like all cancers, endometrial cancer is potentially life threatening. Women who have had a hysterectomy (surgery to remove the uterus) are not at risk for endometrial cancer. BUT if they have had uterine cancer removed, tamoxifen could stimulate metastases or recurrences. 
Women taking tamoxifen in the BCPT had three times the chance of developing a pulmonary embolism (blood clot in the lung) as women who took the placebo (18 women taking tamoxifen versus 6 on placebo). Three women taking tamoxifen died from these embolisms. Women in the tamoxifen group were also more likely to have a deep vein thrombosis (a blood clot in a major vein) than women on placebo (35 women on tamoxifen versus 22 on placebo). Women taking tamoxifen also appeared to have an increased chance of stroke (38 women on tamoxifen versus 24 on placebo). [PDQ document.]

Information about raloxifene [Evista] is limited compared with the data available on tamoxifen because of the shorter time it has been studied (about 5 years) and the smaller number of women who have been studied. Studies of raloxifene have generally involved women who received the drug to determine its effect on osteoporosis, and the duration of both therapy and followup have been short. 

Women taking raloxifene in clinical trials have about three times the chance of developing a deep vein thrombosis or pulmonary embolism as women on a placebo. In osteoporosis studies of raloxifene, the drug did not increase the risk of endometrial cancer. An important part of STAR will be to assess the long-term safety of raloxifene versus tamoxifen in women at increased risk of breast cancer. [PDQ document]. [There has been a report that raloxifene has encouraged the growth of an ovarian cancer. It is not known whether raloxifene would stimulate LMS metastases that are estrogen sensitive.]

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