Effects of tamoxifen on the human female genital tract: review of the literature

Tamoxifen is a non-steroidal triphenylethylene derivate, with clear antioestrogenic effects on the breast, that is orally administrated for the treatment of breast cancer and its prevention in a high-risk population. This article analyzes the effects of tamoxifen on the adult human female genital tract and considers its carcinogenicity in the gynaecological reproductive organs. It has been found that tamoxifen causes oestrogenic changes of the vaginal and cervical squammous epithelium and increases the incidence of cervical and endometrial polyps. The action of tamoxifen on the human endometrium in postmenopausal women is connected with simple oestrogenic effects including hyperplasia, while in others with endometrial cystic atrophy. In cases where tamoxifen induces endometrial polyps and hyperplasia, the extensive fibrosis accounts for difficulties in obtaining endometrial biopsy or resecting the polyps. In premenopausal patients tamoxifen disrupts the menstrual cycles and causes ovarian cysts, while in postmenopausal patients it induces ovarian cystic tumors and endometriomas. Also, postmenopausal patients treated with tamoxifen may develop endometriosis, adenomyosis and leiomyomata. In addition, randomized trials have shown a link between tamoxifen use in breast cancer patients and the development of endometrial carcinomas. Moreover, of note is the fact that the association of tamoxifen therapy with uterine mesenchymal neoplasms is higher than expected. In conclusion, the most worrying gynaecological side-effect of tamoxifen is the well-known increased risk of endometrial carcinomas. Women with breast cancer treated with tamoxifen should undergo annual gynaecological examination, but endometrial sampling should be obtained only in the event of endometrial bleeding.     

Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients

Abstract. Nishimura N, Hachisuga T, Saito T, Kawarabayashi T. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.
This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.     

Molecular genetic characterization of tamoxifen-associated endometrial cancer

OBJECTIVES: The non-steroidal, selective estrogen receptor modulator tamoxifen is currently the most extensively used hormonal agent for the prevention and treatment of estrogen receptor-positive breast cancer. Epidemiologic studies and clinical trials have shown an increased risk of endometrial cancer with tamoxifen exposure; however, few studies have examined these tumors on a molecular level. We sought to elucidate the molecular genetic alterations found in tamoxifen-associated endometrial cancer. METHODS: Twenty-nine breast cancer patients with a history of tamoxifen use who subsequently developed endometrial cancer were retrospectively identified and matched for endometrial histologic subtype and grade to 29 endometrial cancers from breast cancer patients never exposed to tamoxifen. Endometrial tumor tissue was microdissected and genomic DNA extracted for each case. Direct DNA sequencing of the most commonly mutated genes in sporadic endometrial cancer, PTEN, K-RAS, TP53, and CTNNB1, was performed in addition to microsatellite instability (MI) studies. Fisher's Exact Test was utilized for statistical analyses. RESULTS: Of 29 tamoxifen-associated cancers, 10 (34.5%) contained PTEN mutations compared to 13 (44.8%) of the non-tamoxifen-associated cancers (P = 0.59). All PTEN mutations were found in tumors with endometrioid histology, reflecting what is seen in sporadic endometrial cancers. Mutations of K-RAS, TP53, and microsatellite instability were present in similar frequencies between the two breast cancer groups, and moreover, these were similar to mutational frequencies found in sporadic endometrial cancer. CONCLUSION: Tamoxifen and non-tamoxifen-associated endometrial carcinomas arising in women with breast cancer contain similar genetic alterations to those of sporadic endometrial carcinomas.     

Endometrial carcinoma in tamoxifen-treated breast cancer patient: clinicopathological, immunohistochemical, and genetic analysis.

Endometrial polyps and endometrial neoplasms are a recognized complication of chronic tamoxifen treatment. This study describes an endometrial carcinoma that developed in a woman receiving low-dose tamoxifen treatment for breast cancer. Little is known about steroid receptor status, somatic alterations in oncogenes and tumor suppressor genes, and inherited susceptibility in endometrial carcinomas associated with tamoxifen use. In the present case, the endometrial carcinoma was negative for estrogen receptors and weakly positive for progesterone receptors. In addition, analysis of K-ras, c-erbB2/neu, cyclin D1, and p53 status revealed a codon 12 point mutation in the K-ras oncogene. The patient was determined not to be a carrier of germ-line mutations in cytochrome P-450 1A1 (CYP1A1), an estrogen-metabolizing gene previously associated with enhanced endometrial cancer risk, but she was a carrier of a methylenetetrahydrofolate reductase gene variant related with putative alterations in DNA methylation.     

Metastasis from breast carcinoma to a tamoxifen-related endometrial polyp

BACKGROUND: Metastasis of extragenital neoplasms to an endometrial polyp is rare and until now, only 6 cases of such involvement has been described. CASE: A 58-year-old woman, who had been diagnosed 4 years ago with infiltrating ductal breast carcinoma and treated with surgery and tamoxifen therapy, was admitted to the gynecology clinic because of endometrial thickening observed during a routine abdominal ultrasonographic examination. A total hysterectomy with bilateral salpingo-oophorectomy was performed. Pathological examination of the specimen showed a large polyp which microscopically showed clusters of cells with signet ring morphology within the polyp stroma. The positivity of tumor cells for GCDFP-15 supported the diagnosis of metastatic breast carcinoma to endometrial polyp. CONCLUSION: Metastatic breast carcinoma should be considered in the differential diagnosis of carcinomas with signet ring cell morphology involving uterus.     

Association between uterine serous carcinoma and breast cancer

OBJECTIVE: Endometrial cancer and breast cancer are two common malignancies found in women. As a result of estrogen dependency, an association is thought to exist between these entities. This study was undertaken to determine if the endometrial carcinomas, which develop in women with a history of breast cancer, were more likely to be of the endometrioid or the serous histology, which is generally considered non-estrogen-dependent. METHODS: A retrospective chart review was conducted for the years 1984-2001. All women who were diagnosed at our institution with endometrial carcinoma were identified. The women who also had a prior history of breast cancer were identified and comprise the cohort for this study. Information regarding age at diagnosis, tumor stage, histologic subtype, and tamoxifen exposure were recorded and analyzed. RESULTS: About 1166 women were diagnosed with endometrial cancer during the study period, of whom 54 (4.6%) had a pre-existing diagnosis of breast cancer. Of the 54 women in this study, 41 had tumors of the endometrioid histology and 13 had a tumor of the serous subtype. There was no difference with regards to median age at the time of diagnosis or years of tamoxifen exposure. Women with breast cancer were more likely to develop uterine serous carcinoma (USC) as compared to one of endometrioid histology (OR 2.6; 95% CI 1.29-5.23). CONCLUSIONS: Women with breast cancer who subsequently developed endometrial cancer exhibited a 2.6-fold increased risk of developing a USC as compared to an endometrioid carcinoma. These findings suggest that there may be an underlying genetic predisposition linking breast cancer and USC.     

Protein kinase C alpha expression is inversely related to ER status in endometrial carcinoma: possible role in AP-1-mediated proliferation of ER-negative endometrial cancer

OBJECTIVE: Tamoxifen is the most widely used antiestrogen to treat all stages of estrogen-receptor (ER)-positive breast cancers. However, tamoxifen acts as a partial estrogen in the uterus and is known to increase the risk of endometrial cancer by two- to threefold. Recent evidence indicates that there is a connection between tamoxifen resistance and activation of the activator protein-1 (AP-1) pathway. We have previously reported a possible role for overexpression of protein kinase C alpha (PKCalpha), an upstream activator of the AP-1 pathway, in hormone-independent breast cancer and antiestrogen-stimulated endometrial tumors. We hypothesize that alterations of the PKC isozyme profile of endometrial carcinomas are similar to that of hormone-independent breast cancer and determine whether specific PKC isozyme alterations correlated with known clinicopathological features of endometrial cancer. METHODS: The PKC isozyme profile of endometrial carcinomas from 42 patients who were not previously exposed to antiestrogens was examined by Western blot. The relationship between PKC isozyme expression and key prognostic factors for endometrial carcinoma including hormone receptor status, tumor grade, stage, size, and depth of myometrial invasion was examined using the Spearman's rho correlation coefficient. RESULTS: As previously found in breast cancers, PKCalpha and estrogen receptor alpha (ERalpha) expression are inversely related (r(s) = -0.35, P = 0.046). We report significant inverse correlations among ER/progesterone receptor (PR) expression and tumor grade (r(s) = -0.49, P = 0.001 and r(s) = -0.44, P = 0.004, respectively), ER, and depth of myometrial invasion (r(s) = -0.40, P = 0.009). There were no other significant correlations between PKC isozyme expression and other key prognostic factors examined. CONCLUSION: This study indicates that, similar to what was previously observed in breast cancer, PKCalpha and ER expression is inversely related in endometrial cancer. PKCalpha expression may be a useful prognostic indicator in endometrial cancers. A model is offered which describes the putative role of PKCalpha overexpression in activation of the AP-1 pathway and increased proliferation of ER negative endometrial cancers.     

Expression and clinical significance of pepsinogen C in epithelial ovarian carcinomas

OBJECTIVES: To describe the endometrial appearance in postmenopausal breast cancer patients on tamoxifen and to assess a routine surveillance scheme for endometrial lesions. STUDY DESIGN: Three hundred and seventeen postmenopausal breast cancer women already on tamoxifen at the start of the study (group I) and 89 breast cancer women assessed before any tamoxifen intake (group II) underwent an initial and then yearly scans with transvaginal ultrasonography, followed by an hysteroscopy and biopsy for women with an endometrium thickened above 8mm. Endometrial thickness was also measured in 823 women with no breast cancer nor tamoxifen intake (group III). RESULTS: Initial mean endometrial thickness was 8.2mm in group I, 4.4mm in group II and 3.4mm in group III (P<0.001). Eighteen percent endometrial lesions were found in group I and 3.3% in group II. We observed a significant association between endometrial pathology and both cumulated dose and total duration. Polyps were the most frequent and first to appear pathology. Five cancers were detected in group I, and all of them had taken tamoxifen for more than 3 years. CONCLUSION: Our surveillance scheme could be lightened; an acceptable screening scheme might include a baseline assessment before the start of tamoxifen and, if normal, yearly screening after 3 years of tamoxifen therapy, yearly surveillance for women with an abnormal baseline assessment and immediate investigation for symptomatic women.     

The endometrium in breast cancer patients on tamoxifen

We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding. About half of the endometrial specimens showed simple or cystic atrophy, 55–76% had cystic-atrophic polyps or regressive hyperplasia. Depending upon the dose of tamoxifen, 7–19% (30 mg) to 27– 36% (20 mg) showed moderate glandular proliferation. 20–33% had foci of mucinous, clear cell or serous-papillary metaplasia. 68–70% revealed diffuse extensive fibrosis of the endometrial stroma. None of 11 patients biopsied before starting tamoxifen therapy had advanced endometrial glandular proliferation in the second endometrial biopsy after tamoxifen treatment. None of the 19 endometrial neoplasms after tamoxifen therapy was of the endometrioid type: 11 were mucinous adenocarcinomas, 4 clear cell carcinomas, 2 serous-papillary carcinomas, one carcinosarcoma and one malignant Müllerian mixed tumor. The reasons for discrepancies between suspicious sonograms and endometrial atrophy are discussed. Received: January 1999 / Accepted: 11 October 1999     

Pretreatment and prospective assessment of endometrium in menopausal women taking tamoxifen for breast cancer

OBJECTIVES: To estimate the pretreatment incidence of endometrial pathology and to prospectively assess the endometrial morbidity emerging during tamoxifen intake for breast cancer. STUDY DESIGN: One-hundred and forty-six menopausal breast cancer patients, candidate to receive tamoxifen underwent endometrial assessment by Transvaginal Ultrasonography (TU) before the start of therapy. A double-layered endometrial stripe measuring more than 4mm indicated hysteroscopy and endometrial biopsy. Endometrial abnormalities detected before the start of tamoxifen were treated by operative hysteroscopy or by hysterectomy; no therapy and yearly hysteroscopic follow-up was scheduled for patients showing non-atypical hyperplasias. All women were asked to undergo TU on a yearly basis; during the follow-up period, indication for hysteroscopy and endometrial biopsy were the following: (i) an endometrial lining measured above 4mm at the first time, (ii) at least a 50% increase of endometrial thickness since the last finding in patients previously assessed by hysteroscopy, (iii) a recorded vaginal bleeding, and (iv) previous findings of endometrial hyperplasia. Histopathologic result from biopsy or hysterectomy was the reference test to establish the baseline prevalence of endometrial pathology and the emerging prevalences of morbidity after 12, 24, 36, 48 and 60 months of tamoxifen therapy. RESULTS: One-hundred and five patients were followed for 60 months, whereas 113, 126, 137 and 141 patients were evaluated up to 48, 36, 24 and 12 months, respectively. In 44 out of 146 patients, pretreatment TU showed an endometrium thicker than 4mm and in 31 (21.2%) of these patients abnormalities consisting of 16 endometrial polyps, seven polyps harboring simple hyperplasia, four simple hyperplasias, three atypical hyperplasias and one adenocarcinoma were found. During tamoxifen intake benign endometrial abnormalities were detected in 36 out of 114 assessable patients showing normal endometrium before the start of tamoxifen therapy (31.5%) and in seven out of 27 patients with baseline endometrial abnormalities (25.9%). Overall, an endometrial pathology emerged in 30.4% of patients during tamoxifen administration and in no patients we found an atypical lesion. CONCLUSIONS: In menopausal breast cancer patients the incidence of endometrial abnormalities before the start of tamoxifen therapy is high and includes 2.7% of atypical pathology. After the diagnosis and treatment of baseline atypical lesions were accomplished, no atypical endometrial lesion emerged after the start of tamoxifen administration. Based on these findings, we believe that pretreatment assessment of endometrium is recommended in all menopausal women candidate to receive tamoxifen therapy.     

Does tamoxifen use affect prognosis in breast cancer patients who develop endometrial cancer?

OBJECTIVE: The use of tamoxifen to prevent breast cancer and decrease recurrence is not controversial. However, the effect that tamoxifen may have in women with a history of breast cancer in whom endometrial cancer develops is unclear. The purpose of this study was to estimate whether a history of tamoxifen use is a prognostic factor for such patients. METHODS: Between 1990 and 2002, patients seen at The University of Texas M. D. Anderson Cancer Center with a history of breast cancer who developed endometrial cancer were identified. Medical records were reviewed to identify clinical, pathologic, and outcome information. RESULTS: Eighty-nine patients with a history of breast cancer in whom endometrial carcinoma developed were identified. Fifty-two percent (46/89) had a history of tamoxifen use (median duration 48 months; range 2-120 months). There were no significant differences in the clinical or pathologic features between tamoxifen users and nonusers. A history of tamoxifen use was associated with a shorter interval from breast cancer to endometrial cancer diagnosis (77.2 versus 121.3 months for nonusers; P =.01). There was no significant difference in overall survival between tamoxifen users and nonusers (39.2 months versus 48.3 months, P =.27), and there was no difference in endometrial cancer-specific survival duration between tamoxifen users and nonusers (55.7 versus 51.0 months, P =.92). CONCLUSION: Among tamoxifen users, the interval from breast cancer to endometrial cancer diagnosis was significantly shorter than that in nonusers. In this cohort, a history of tamoxifen use was not associated with a worse overall or disease-specific survival.     

Recurrent endometrial polyps in postmenopausal breast cancer patients on tamoxifen

OBJECTIVES: Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure, with an incidence of up to 10.7% of malignancy. Some women tend to develop recurrent polyps. However, no one has yet described any risk factors for the development of recurrent endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients. METHODS: We compared various clinical features of 64 postmenopausal breast cancer tamoxifen-treated patients with a primary endometrial polyp (Group I), with those of 27 similar patients with recurrent polyps (Group 2). RESULTS: Previous exposure to hormone replacement therapy was significantly more common and duration of tamoxifen treatment, up to the diagnosis of primary endometrial polyp, was significantly shorter in Group II patients (P = 0.0217 and P = 0.0148, respectively). Logistic regression analysis revealed that the combination of shorter tamoxifen exposure before the diagnosis of primary polyp, lower parity, lower menopausal age at the diagnosis of primary polyp, and higher years of tamoxifen treatment was found to increase significantly the risk of developing recurrent endometrial polyps. Any additional year of tamoxifen treatment may increase by fivefold the risk of developing recurrent polyps. There was no significant difference in ultrasonographic endometrial thickness measured before resection of the primary polyps in both groups and before the resection of recurrent polyps in Group II. CONCLUSIONS: Previous use of HRT, shorter duration of tamoxifen exposure, and additional years of tamoxifen treatment may significantly increase the risk of developing recurrent endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients.     

Ovarian cysts in postmenopausal tamoxifen-treated breast cancer patients with endometrial thickening detected by transvaginal sonography

OBJECTIVE: To investigate the frequency of ovarian cysts in tamoxifen-treated postmenopausal breast cancer patients with endometrial thickening detected by transvaginal sonography. METHODS: Medical records and transvaginal sonographies of 38 postmenopausal women treated for breast cancer with adjuvant tamoxifen therapy who had undergone endometrial sampling due to abnormal endometrial thickness were reviewed retrospectively. RESULTS: During the study period five of 38 tamoxifen-treated postmenopausal patients (13.2%) had ovarian cysts. The mean tamoxifen treatment interval of the patients with an ovarian cyst was 22.4 +/- 18.4 months (p = 0.17). The mean endometrial thickness of the patients with an ovarian cyst was 12.6 +/- 5.9 mm (p = 0.17). Endometrial biopsy detected six cases of abnormal endometria, including endometrial carcinoma (n = 1), endometrial polyp (n = 1) and simple endometrial hyperplasia without atypia (n = 4). Three patients with ovarian cysts underwent laparatomy revealing simple cysts on histopathological examination. Two patients with ovarian cysts declined laparatomy and are currently under follow-up. CONCLUSION: Ovarian cysts a common side-effect of tamoxifen treatment in postmenopausal tamoxifen-treated breast cancer patients. Transvaginal sonography should be performed to detect any concomitant endometrial pathology.     

Estrogen receptor expression in an endometrial stromal sarcoma after tamoxifen therapy

INTRODUCTION: Several cases of low-grade endometrial stromal sarcomas in women with breast cancer have been reported to be associated with tamoxifen therapy. Estrogen receptor expression has been used to characterize the partial estrogenic action of tamoxifen on the endometrium and has been found in tamoxifen-associated endometrial pathologies. CASE: A low-grade endometrial stromal sarcoma in a woman with a history of breast cancer treated with adjuvant tamoxifen is presented. Steroid receptor studies performed on the tumor were negative for estrogen and positive for progesterone. CONCLUSION: The absence of estrogen receptor expression suggests that endometrial stromal sarcomas are not necessarily caused by the estrogenic properties of tamoxifen.     

Histopathologic behavior of endometrial hyperplasia during tamoxifen therapy for breast cancer

OBJECTIVE: The purpose of the present study is to prospectively evaluate the effects of tamoxifen on the pathological behavior of endometrial hyperplasias without atypia, diagnosed before the start of adjuvant endocrine therapy, in menopausal patients suffering from breast cancer. METHODS: Twenty-six patients suffering from estrogen-receptor positive breast cancer and candidate to receive adjuvant tamoxifen, were found to be affected by endometrial hyperplasias before the start of endocrine therapy. All women showed a baseline endometrial stripe, measured by transvaginal ultrasonography, thicker than 4 mm and the diagnosis of endometrial hyperplasia was made by hysteroscopy and endometrial biopsy. Two patients showing complex atypical hyperplasia underwent vaginal hysterectomy, whereas the remaining 24 patients, suffering from endometrial hyperplasia without atypia, were followed on a yearly basis during the period of tamoxifen intake, by hysteroscopy and endometrial biopsy. RESULTS: Baseline histopathology showed simple and complex hyperplasia in 20 and in 4 patients, respectively. The median follow-up period was 38 months; in particular, all patients underwent endometrial assessment after 12 months, while 22, 16, 10 and 4 patients were followed-up after 24, 36, 48 and 60 months of tamoxifen therapy, respectively. Progression from complex hyperplasia to complex atypical hyperplasia (1 patient) and from complex and simple hyperplasia to adenocarcinomas (2 patients) was found within 24 months of tamoxifen intake in 3 patients (12.5%). In 2 patients (8.3%), a progression from simple to complex hyperplasia was detected within 36 months of tamoxifen treatment. In 13 patients (54.1%), stable histology of simple or complex hyperplasia was found, whereas 6 patients (25.0%), with focal hyperplasia harbored in an endometrial polyp, showed a normalization of endometrial histology after polyp resection. CONCLUSIONS: Endometrial hyperplasias without atypia diagnosed before endocrine therapy for breast cancer in menopausal patients show an early and high progression-rate to atypical lesions under tamoxifen influence.     

Endometrial pathology of 104 postmenopausal breast cancer patients treated with tamoxifen

OBJECTIVE: To investigate the effects of tamoxifen on the endometrium in postmenopausal breast cancer patients. METHODS: Endometrial thickness was measured by transvaginal sonography and endometrial biopsies were done in 104 postmenopausal breast cancer cases who were treated with tamoxifen. Histopathologic findings were discussed. RESULTS: Mean endometrial thickness was 11.7+/-5.9 mm and duration of tamoxifen administration was 35.3 months. Four endometrial cancers, 17 endometrial hyperplasias, 25 proliferative endometrium, 5 endometrial polyps in the endometrial biopsies. We observed atrophic endometrium in 53 of the cases. Only one case with endometrial polyps was observed as a premalignant lesion when the endometrium was less than 5 mm, 51% of the cases had thicker endometrium (more than 10 mm) and 32% of these cases had malignant and premalignant endometrium. We found a significant correlation with the duration of tamoxifen and age (p<0.05). One hundred and two of our cases were asymptomatic; only 2 out of 4 endometrial cancer cases had vaginal spotting. A significant relation was noticed between endometrial thickness and duration of tamoxifen treatment (p=0.025). CONCLUSION: It was concluded that positive endometrial findings and endometrial thickness were due to continuous unopposed tamoxifen treatment and our findings support the hypothesis that tamoxifen increases the risk of endometrial carcinoma and premalignant changes.     

Gynaecological Complications of Women Treated with Tamoxifen for Breast Cancer

Summary: We present 6 cases illustrating some of the gynaecological complications associated with tamoxifen treatment of women with breast cancer. The first 2 represent cases of myometrial hypertrophy secondary to tamoxifen use, a postmenopausal woman and a premenopausal women with recurrent carcinoma of the breast. The third is a case of probable ovulation induction in a perimenopausal woman with recurrent breast cancer who was commenced on tamoxifen 20 mg daily. The other 3 cases illustrate some of the endometrial effects associated with tamoxifen therapy in women with a history of breast cancer, namely cystic glandular hyperplasia, endometrial polyps and endometrial cancer.     

Ultrasonography of the endometrium and endometrial pathology under tamoxifen treatment

PURPOSE: The estrogenic effects of tamoxifen on the endometrium and the vaginal epithelium are evaluated. METHOD: 211 postmenopausal women were examined (tamoxifen group: 176 estrogen-receptor positive breast cancer patients; control group I: 35 estrogen-receptor negative breast cancer patients; control group II: 50 women without breast cancer taking no hormones). We determined the endometrial thickness and the maturation index (MI). Person's chi-square-test and the t-test for independent samples were used. RESULTS: In the tamoxifen group, the mean endometrial thickness and the MI were significantly higher (p<0.0001) than in the control groups. No evidence of correlation in duration of tamoxifen intake and endometrial thickness was found (Pearson's correlation coefficient: 0.4773; p=0.0001). The maturation index significantly (p<0.0001) increased under tamoxifen therapy. There was no correlation in the maturation index and endometrial thickness (Pearson's correlation coefficient: 0.1649; p=0.169). The histological clarification (N=47; endometrial thickness greater than 8 mm) revealed 3 neoplasms, 9 endometrial polyps, 2 glandular-cystic hyperplasias and in 32 cases atrophic endometrium. CONCLUSION: An apparent increase of endometrial thickness and the maturation of the vaginal epithelium caused by the estrogenic effect of tamoxifen was demonstrated.     

Failure of megestrol acetate to reverse tamoxifen induced endometrial neoplasia: two case reports

Abstract. Rose PG, Brandewie EV, Abdul-Karim FW. Failure of megestrol acetate to reverse tamoxifen induced endometrial neoplasia: two case reports.
Tamoxifen's agonist effect on the endometrium has been associated with an increased incidence of endometrial carcinoma. It has been suggested that this agonist effect may be averted by the concomitant use of a progestational agent. We report two patients with breast cancer receiving tamoxifen who developed endometrial carcinoma and atypical endometrial hyperplasia, respectively. In one patient, this occurred despite the use of concomitant megestrol acetate. In the other patient, tamoxifen-associated endometrial hyperplasia persisted and progressed despite cessation of tamoxifen and initiation of megestrol acetate therapy. These cases may have implications for strategies to avert tamoxifen induced endometrial neoplasia.     

Evaluation of endometrium during tamoxifen therapy of breast cancer

Tamoxifen is one of most common drugs for breast cancer therapy. But its weak estrogenic activity in endometrium can be the source of different abnormalities including even endometrial cancer. OBJECTIVES: The aim of this clinical trial was to compare ultrasound scan results, hysteroscopy and pathomorphological findings of tamoxifen treated patients with breast cancer who complained of bleeding. MATERIALS AND METHODS: Analyzed group consisted of 10 patients treated for abnormal endometrium during breast cancer tamoxifen therapy. RESULTS: Among 10 examined women 7 presented no pathological changes, there was 1 case of simple benign hypertrophy and 2 cases of endometrial polyps. CONCLUSIONS: There is no exact correlation between ultrasound scan results and pathomorphological findings in patients treated with tamoxifen for of breast cancer. Transvaginal ultrasound examination is not efficient screening test for endometrial abnormalities during tamoxifen therapy.