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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogens are important for both normal cell growth and malignant proliferation in the mammary gland as well as in the endometrium. Tamoxifen is a non-steroidal anti-estrogen widely used in breast cancer treatment. In recent years reports have been made of an increased risk of endometrial carcinoma during tamoxifen treatment. We used surgically menopausal cynomolgus macaques to study proliferation and p53 expression during hormonal replacement therapy (HRT) and tamoxifen treatment. Animals were treated continuously for 35 months with either conjugated equine estrogens (CEE; n = 20); medroxyprogesterone acetate (MPA; n = 17); the combination of CEE + MPA (n = 13); or tamoxifen (n = 17) for 35 months. We found an increased expression of p53 in normal breast and endometrial tissue linked to CEE but not tamoxifen treatment. In the breast alveoli there was an association between proliferation measured by morphometry and p53 expression in all groups. However, in the endometrium CEE induced significantly more p53 positivity than tamoxifen, 9/20 vs. 3/17 in glands and 9/19 vs. 0/17 in stroma, respectively. If indeed long-term treatment with tamoxifen as in the present study could inactivate the tumor-suppressive function of p53, endometrial cells might thereby become more susceptible to genetic lesions associated with carcinogenesis.
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PMID:p53 expression in breast and endometrium during estrogen and tamoxifen treatment of surgically postmenopausal cynomolgus macaques. 1020 73

Two women with endometrial carcinoma who wished to preserve their childbearing ability received conservative treatment by medroxyprogesterone acetate (MPA, 600 mg/day for 22 weeks and 29 weeks, respectively). Following regression of endometrial lesions, their infertility was treated by inducing ovulation. Intact pregnancy was diagnosed 13 months and 11 months after completion of the MPA treatment, respectively. One patient had a twin pregnancy and delivered two infants at 35 weeks of gestational age. The other patient delivered a full-term baby. They had no evidence of recurrence 60 months and 31 months after the conservative treatment, respectively. We believe this conservative treatment with progestin may be safely performed for young patients with endometrial cancer who wish to preserve their fertility.
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PMID:Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: report of two cases. 1084 66

BACKGROUND: Postoperative adjuvant tamoxifen (TAM) therapy in breast cancer patients may lead, albeit rarely, to endometrial cancer. Preventive measures are urgently needed. METHODS: The study subjects were postmenopausal women who had undergone surgery for breast cancer. The control group (n=10) received no further therapy. Patients who had completed adjuvant TAM therapy were assigned to a medroxyprogesterone acetate (MPA;400 mg/day orally for 4 weeks) group (n =15) or no MPA treatment group (no MPA group)(n=15). Uterine cervix cytodiagnosis was performed after completing the TAM therapy(initial), and 4(4-week)and 16(16-week)weeks later. The serum 17beta-estradiol (E2) and progesterone concentrations were measured initially and at 4 weeks. The karyopyknotic index (KPI), eosinophilic index (EI) and maturation index (MI) were calculated from Papanicolaou-stained specimens. RESULTS: The background parameters showed no biases. There were no differences in the PKI or El between the no MPA and MPA groups. However, regarding the MI, after 4 weeks in the MPA group, the intermediate cells were significantly increased, while the superficial cells tended to be significantly decreased. Regarding the percent change from the initial value, after 4 weeks in the MPA group, the KPI and superficial cells were significantly decreased, and the intermediate cells were significantly increased. The estrogen activity level and the progesterone concentration were significantly lower in the MPA group compared with the no MPA group. CONCKLUSIONS: The MPA administration clearly lowered the estrogenic activity, indicating that MPA therapy should be effective in reducing the risk of TAM-associated endometrial cancer.
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PMID:Suppression of Estrogenic Activity by Medroxyprogesterone Acetate in Tamoxifen-treated Patients after Surgery for Breast Cancer to Reduce the Risk of Endometrial Cancer Development. 1109 50

Estrogen replacement therapy (ERT) increases a woman's risk of developing endometrial cancer approximately 120% for each 5 years of use. ERT increases a woman's risk of developing breast cancer approximately 10% for each 5 years of use. To reduce the greatly increased endometrial cancer risk, progestins have been added to ERT (estrogen-progestin replacement therapy; EPRT) for between 5 and 15 days (usually 7 or 10 days) per month in a sequential fashion (sequential EPRT; SEPRT) or with each dose of ERT (continuous-combined EPRT; CEPRT). We conducted two large case-control studies in postmenopausal women in Los Angeles to evaluate the effects of these changes on endometrial and breast cancer risks. As expected CEPRT was not associated with any increased risk of endometrial cancer. SEPRT with the progestin being given for 10 days per month also did not increase endometrial cancer risk. SEPRT with the progestin being given for 7 days per month did increase endometrial cancer risk with only a relatively slight reduction in risk compared to ERT effectively proportional to the reduction in the number of days of unopposed estrogen. The sharp contrast between the effects of 7 days and 10 days of progestin in SEPRT suggests that the extent of endometrial sloughing or of 'terminal' differentiation at the completion of the progestin phase may play a critical role in determining endometrial cancer risk. This may provide an explanation of why endometrial cancer risk increases so sharply with age in young women even in countries where obesity-associated anovulation is very uncommon; extended periods of unopposed estrogen is not an explanation but less than 10 days of an 'adequate' progesterone level may be. EPRT significantly increased the risk of breast cancer. EPRT was associated with an approximately 24% increase in risk for each 5 years of use; the effect was some 212-fold greater than the effect of ERT, which we had previously predicted on theoretical grounds. This effect could also be predicted from the results on mammographic densities seen in the PEPI randomized trial of different forms of hormone replacement therapy (HRT). In the PEPI trial EPRT increased mammographic densities to a much greater extent than ERT. Progestins need to be given to protect the endometrium. They need to be delivered to the endometrium in a manner that will have the least effect on the breast. This can be carried out by using a vaginal or direct endometrial route of administration. The vaginal route will provide adequate endometrial progestin levels with low blood levels so that the effects of the progestin on the breast should be small; with the direct endometrial route the blood progestin levels are even lower, and the effects of the progestin on the breast will be effectively zero. If this is unacceptable to a woman, then giving progestins by mouth (or transdermally) for 10 days every 3 to 4 months should provide satisfactory protection of the endometrium when used with standard-dose conjugated estrogen (CE). This regimen has much less effect on the breast than monthly SEPRT or CEPRT. Two clinical trials of 10 mg per day of MPA for 14 days every 3 months and 0.625 mg/day of CE have been published. Both studies suggest that this approach may be satisfactory in that the extent of hyperplasia was minimal. More studies of this approach are urgently needed.
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PMID:Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer. 1110 73

Fifteen cases of endometrial cancer were administered daily doses of 600 mg of MPA after surgery to prevent the recurrence of cancer. The initiation times of coagulation (time necessary for fibrin network formation) were measured with a highly sensitive damped oscillation rheometer and compared with those of 15 control patients who were not administered MPA. Biochemical studies of blood coagulation and fibrinolysis were also done. The initiation times of coagulation were 19.0+/-1.8 minutes (min mean +/- standard deviation) after 3-6 months and 16.0+/-2.0 min after 9-12 months of MPA administration, both times being significantly shorter compared with the controls (24.0+/-2.5 min). Hematocrit values, platelet counts and fibrinogen levels were similar between the two groups. Activated partial thromboplastin time (APTT) was significantly decreased and antithrombin III activity (AT III), thrombin-antithrombin complex (TAT), plasminogen level, plasmin-alpha(2) plasmin inhibitor complex level (PIC) and the fibrin degradation product level (FDP) were significantly increased in the MPA group compared with the control group. Accelerated coagulation of blood was definitely induced by high-dose MPA but antithrombin and fibrinolytic activities were also induced, and, thus, thromboembolic complications were prevented.
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PMID:Effect of high-dose progestogen on hemostatic properties of blood in patients with endometrial cancer. 1138 Nov 84

Recently, the number of cases of endometrial cancer has increased in Japan. Most of the increase are accounted for by premenopausal cases, which are frequently positive for ER or PR. Hormonal treatment using progestins such as MPA has been widely applied to endometrial cancer patients under 40 years old under the conditions of grade 1 well-differentiated endometrioid adenocarcinoma without myometrial invasion. In our hospital, we applied high-dose (600 mg/day) MPA for over 8 weeks in 14 cases of endometrial cancer, of which adenocarcinoma disappeared in 12 cases (86%), followed by cyclic administrations of low-dose MPA, with 7 subsequent recurrences. We think that a protocol for improving ovarian function, such as active induction of ovulation, should be established to induce intrinsic progesterone sufficient for the prevention of the recurrence of endometrial cancers. In the 2 cases, in which adenocarcinoma remained even after long administrations of MPA, myometrial invasion was noted in the surgically resected specimens. For advanced or recurrent endometrial cancers, MPA has been reported to be effective in an average of 26% in several reports, and effective in 42% cases when applied with combination chemotherapy, such as CAP, by virtue of the "chemical modulator" effect, which can delay the acquired resistance against ADM or CDDP. Furthermore, MPA has resulted in a significant improvement of 5-year disease-free survival rate when used as adjuvant therapy after complete operations and whole pelvic irradiation, compared with administrations of 5-FU in a randomized controlled study in Japan. Thus, in the future, we consider that hormonal therapy will play a more important role in endometrial cancer treatment.
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PMID:[Hormonal therapy for endometrial adenocarcinoma]. 1147 42

Two injectable forms of hormonal contraception, depot medroxyprogesterone acetate (DMPA, Depo-Provera) and medroxyprogesterone acetate/estradiol cypionate (MPA/E(2)C, Lunelle), are now available to American women. Both formulations have demonstrated high degrees of efficacy, safety, and ease of use in international and U.S. trials. Data on DMPA have shown a number of noncontraceptive and therapeutic benefits, the most prominent of which is an 80% reduction in the risk of endometrial cancer. Although such benefits are less documented for MPA/E(2)C, they are expected to be similar to those seen with DMPA and oral contraceptives. Minor side effects of both formulations include menstrual irregularities in the early months of treatment and amenorrhea with DMPA. Patient counseling about the potential for these side effects, as well as possible risks, is important to long-term successful use of these contraceptive methods.
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PMID:Current options for injectable contraception in the United States. 1172 75

To study the functional differences between the two progesterone receptor isoforms (hPRA and hPRB) in human endometrial cancer, two new endometrial carcinoma cell lines were created-one expressing hPRA and one expressing hPRB.A well-differentiated, hPR-negative Ishikawa cell line was stably transfected with either hPRA or hPRB cDNA. Transfected cells were selected, and two cell lines expressing approximately equal amounts of receptor were isolated-one expressing hPRA (PRA-14) and one expressing hPRB (PRB-59). Cell growth experiments revealed a growth-inhibitory response to progestins (MPA and R5020) in the PRB-59 cells but not in the PRA-14 cells. Differences in expression of genes targeted by the two isoforms were studied using a cDNA expression array technique. A different set of genes appeared to be progesterone regulated in the PRA-14 cells than in the PRB-59 cells. None of the genes were regulated by both hPRA and hPRB. Insulin-like growth factor binding protein 3 expression was studied in more detail as an example of a gene regulated in PRB-59 cells but not in PRA-14 cells. We established a new model to study functional differences between the two hPR isoforms in human endometrial carcinoma cells. This model revealed distinctive differences in target gene regulation between the two hPR isoforms. Moreover, antiproliferative actions of progesterone on human endometrial cancer cells could be observed only in the PRB-expressing cell line.
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PMID:Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. 1251 94

To clarify what constitutes the adequate management of uterine endometrial carcinoma in young women, we reviewed clinicopathologically 31 patients aged 40 years and younger between January 1991 and June 2004. As a primary treatment, 12 cases chose hormonal treatment with medroxyprogesterone acetate (MPA; 600 mg/day) due to no findings of myometrial invasion and diagnosis of a grade 1, well-differentiated adenocarcinoma. In remaining 19 cases, surgery was performed. All the 19 patients who received surgery as a primary treatment are alive, with no evidence of a recurrence of the disease. In the 12 patients who received hormonal treatment, 8 patients eventually received a hysterectomy because of recurrence or no response to MPA. Of these eight patients, myometrial invasion was recognized in three patients. One of the eight patients died of the metastasized disease to the liver and brain after hysterectomy. After hormonal treatment, 4 of the 12 patients were exempted from surgery and showed no evidence of recurrence. Two patients had viable children. Progesterone receptor was negative in one case that died. Careful consideration should be given to hormonal treatment with MPA for the conservative management of endometrial carcinoma in young women. Moreover, MPA is not always a consistent management for every patient.
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PMID:Clinicopathologic study of uterine endometrial carcinoma in young women aged 40 years and younger. 1601 20

The study was undertaken to investigate the effect of long-term treatment with MPA on the growth and invasiveness of endometrial carcinoma Ishikawa cells and the expression of the subtype of estrogen receptor and progesterone receptor. The human endometrial carcinoma Ishikawa cells were continually exposed to 2.5 micromol/L step-wise increase of MPA. MTT assay, flow cytometry and Matrigel invasion assay were used to detect the effect of MPA on the growth, cell cycle distribution and the invasion capability of the cells respectively. RT-PCR was performed to detect the changes of CyclinD1, MMP2 and MMP9 over different time treatment of MPA. Immunocytochemistry was used to examine the expression of estrogen receptor subtype and progesterone receptor subtype. Endometrial carcinoma Ishikawa cells became resistant to the inhibitory effect of MPA over ten months MPA treatment. The cells resistant to the growth inhibitory effect were named progestin-resistant Ishikawa cells and the cells which the progestin-resistant originated from were named the parent Ishikawa cells. The effects of MPA shifted from growth and invasiveness inhibitory effects on the parent Ishikawa cells to stimulatory effect on the progestin-resistant Ishikawa cells. Consistent with the phenomena, the treatment with MPA on Ishikawa cells resulted in statistically significant decreases of CyclinD1, MMP2 and MMP9 gene expression, reversely, the treatment with MPA on the progestin-resistant Ishikawa cell resulted in statistically significant increases of CyclinD1, MMP2, MMP9 gene expression. Immunocytochemical analysis showed reduced ERalpha and PR-B expression and increased ERbeta expression in the progestin-resistant Ishikawa cells compared with parental Ishikawa cells. From the experiment, it was concluded that the prolonged treatment with MPA on Ishikawa cell could give rise of the resistant effect of MPA, the effect of MPA on the growth and invasiveness capability of endometrial carcinoma shifted from inhibitory to stimulatory. The imbalance of ER subtype and PR subtype might contribute to the mechanisms involved in the progesterone resistance over long-term MPA treatment.
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PMID:[Influence of long-term treatment with MPA on the biological character of endometrial carcinoma Ishikawa cell]. 1758 Jun 63


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