Prospective assessment of the endometrium in postmenopausal breast cancer patients treated with fulvestrant

This prospective study assessed the endometrial effects of fulvestrant, a pure estrogen-receptor antagonist, in postmenopausal women with breast cancer. This single-center study enrolled postmenopausal patients who had an intact uterus at baseline with progressive metastatic breast cancer on tamoxifen followed by an oral aromatase inhibitor (AI). Fulvestrant (250 mg) was administered every 28 ± 3 days via IM injection. Transvaginal ultrasonography (TVUS) was performed at baseline and after 3 months of therapy. Primary and secondary endpoints were changes from baseline in double endometrial thickness (DET) and uterine volume (UV), respectively. No interventions were performed on any asymptomatic uterine abnormalities that were detected at baseline. In total, 32 women were enrolled. Five patients had no repeat TVUS because of early progression before 3 months, leaving 27 evaluable patients for final analysis. After 3 months therapy, mean DET had significantly decreased by 23.08% (P = 0.010). Mean UV also decreased by 10.88%, although this change was not significant (P = 0.119). After 3 months of therapy, none reported vaginal bleeding, there were no changes noted in most of the uterine pathologies present at baseline and no new uterine abnormalities were detected. We observed that 3 months of fulvestrant treatment resulted in a significant decrease in endometrial growth and a non-significant decrease in UV in postmenopausal women with metastatic breast cancer previously exposed to tamoxifen and AIs. Furthermore, no new uterine pathologies were detected, indicating that fulvestrant behaves as a pure antiestrogen at the uterine level.     

乳腺癌子宫内膜转移3例临床病理分析

目的 探讨乳腺癌子宫内膜转移的临床病理特征、治疗及预后。方法 回顾性分析3例乳腺癌子宫内膜转移患者的临床资料并结合文献复习。结果 3例乳腺癌子宫内膜转移患者中乳腺浸润性小叶癌2例,浸润性导管癌1例。子宫内膜转移灶直径为3~8 cm,中位直径4.5 cm。镜下见子宫内膜转移灶癌细胞呈圆形或椭圆形,细胞质较丰富,部分癌细胞异型性明显,排列呈管状。束状或索状分布,部分区域见小叶样结构。原发灶、子宫内膜转移灶ER、PR、Ki-67均呈阳性表达,CerbB-2、GCDFP-15、E-cadherin染色呈差异性表达,CK7、P120呈局灶阳性,CK5/6、SMA、CD10和S-100呈阴性。结论 乳腺癌伴子宫内膜转移临床少见,预后较差,生存期较短,确诊主要依靠病理和免疫组化检查,ER、PR、CK5/6、CK7、CerbB-2及GCDFP-15对子宫内膜原发癌与转移癌有一定鉴别作用。     

Uterine Malignancy following Tamoxifen Use in Breast Cancer Patients in Iran: Case Series and Literature Review

Background: This study evaluated tumor characteristics and survival in women with breast cancer whosubsequently developed uterine cancer. Methods: Information about endometrial cancer in tamoxifen usersfollowing breast cancer refered to the gynecologic oncology clinic of Vali-Asr hospital between 1997-2007 wasevaluated. Results: Among 330 patients with endometrial cancer, 5 were in women previously diagnosed withbreast cancer. Two cancers were malignant mixed Mullerian tumors of the uterus (MMMT), 2 were endometrioidadenocarcinomas, and one was a papillary clear cell carcinoma. Patients received tamoxifen for 4-8 years. Theendometrial cancers occurred 2-11 years after initial treatment for the breast cancers. Four of the endometrialcancers featured abnormal uterine bleeding and one of them had increased vaginal discharge and all werediagnosed on endometrial curetting. All patients received standard surgical staging for endometrial cancer andall except one were stage I. At laparotomy of one patient, an advanced stage MMMT was found with diffusedperitoneal spread and ascites. In spite of the surgery, she died of disease, 3 months later. The other patientsremain recurrence-free for breast cancer and uterine cancer after 6-120 months. Conclusion: Breast cancerpatients who use tamoxifen and have early stage endometrial cancers demonstrate a good prognosis. Abnormaluterine bleeding or vaginal discharge is the most important symptom.     

Third generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients.

BACKGROUND: Tamoxifen may induce uterine abnormalities of clinical concern. Our aim was to compare early uterine changes occurring in postmenopausal breast cancer patients treated in first-line with tamoxifen or third generation aromatase inhibitors. We also assessed the effect of aromatase inhibitors on tamoxifen-induced uterine changes. PATIENTS AND METHODS: Seventy-seven consecutive postmenopausal breast cancer patients scheduled to start endocrine treatment were included in this prospective study. Transvaginal ultrasonography (TVUS) was carried out before and after 3 months of therapy. No interventions were done on pre-existing asymptomatic uterine abnormalities seen on baseline sonography. RESULTS: After 3 months of therapy, tamoxifen significantly increased endometrial thickness and uterine volume. Additionally, 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 pathologies seen under tamoxifen. Furthermore, aromatase inhibitors decreased endometrial thickness and uterine volume in patients previously treated with tamoxifen. CONCLUSIONS: Our study demonstrates that tamoxifen induces uterine abnormalities from as early as 3 months of therapy. In contrast, these abnormalities are not seen in patients on aromatase inhibitors. Furthermore, our data indicate that tamoxifen therapy followed by an aromatase inhibitor may lead to a reduction in endometrial pathologies associated with tamoxifen.     

Effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on serum hormones and bone characteristics in a preclinical tumor model for breast cancer.

PURPOSE: The purpose of this study was to evaluate and compare the effects of the antiestrogen tamoxifen and the aromatase inhibitor letrozole on tumor growth, serum hormones, uterine weight, body composition, and bone characteristics in mice. EXPERIMENTAL DESIGN: Human estrogen-dependent breast cancer cells stably transfected with the aromatase gene (MCF-7CA cells) were inoculated in Matrigel subcutaneously into ovariectomized nude mice. This model represents postmenopausal breast cancer in many respects, including the fact that estrogen is no longer produced by the ovaries and is not under feedback regulation by gonadotropins. Mice that received subcutaneously implanted MCF-7CA cancer cells were then treated with tamoxifen or letrozole for 7 weeks. RESULTS: As reported previously, tumor growth was markedly inhibited by both tamoxifen (100 microg/day) and letrozole (10 microg/day). Tamoxifen treatment led to increased bone mineral density (BMD) and hyperplastic uteri. Mice treated with letrozole had significantly smaller uteri than the controls and tamoxifen-treated mice. Letrozole did not affect BMD. There was no significant difference in systemic leptin and insulin-like growth factor I levels as a result of tamoxifen or letrozole treatment. CONCLUSIONS: Tamoxifen treatment inhibited breast cancer cell growth and increased BMD but caused uterine hypertrophy in this preclinical model of postmenopausal breast cancer. Letrozole inhibited tumor growth without inducing uterine hypertrophy. In addition, letrozole had no effect on BMD. These findings provide experimental evidence that letrozole is an effective and safe (in terms of risk of endometrial cancer risk and osteoporosis) alternative or complement to tamoxifen treatment for breast cancer.     

Effects of raloxifene after tamoxifen on breast and endometrial tumor growth in athymic mice

BACKGROUND: In patients with early-stage breast cancer, 5 years of treatment with the selective estrogen receptor modulator (SERM) tamoxifen reduces breast cancer recurrence and mortality, whereas more than 5 years of tamoxifen does not further reduce breast cancer recurrence and doubles the risk of endometrial cancer. We evaluated the effects on tumor growth of raloxifene, another SERM, after tamoxifen treatment in mouse models of breast and endometrial cancers. METHODS: Athymic, ovariectomized mice were bitransplanted with tumors derived from human breast cancer and endometrial cancer cells that either were tamoxifen-naive or had been exposed to tamoxifen for short (6 months) or long (>5 years) terms. The effects of raloxifene (two dose levels) and tamoxifen on tumor growth in the presence and absence of low-dose estrogen were evaluated. All statistical tests were two-sided. RESULTS: Raloxifene was less effective than tamoxifen in blocking the stimulatory effects of low-dose estrogen on the growth of tamoxifen-naive breast (P<.001) and endometrial (P =.001) tumors. Raloxifene and tamoxifen had similar inhibitory effects on the growth of short-term tamoxifen-exposed breast tumors. Raloxifene and tamoxifen had similar stimulatory effects on the growth of breast and endometrial tumors that had been exposed to at least 5 years of tamoxifen. However, neither drug blocked the stimulatory effects of estrogen on the growth of these tumors. Raloxifene was less effective than tamoxifen (P<.001) in blocking the stimulatory effects of estrogen on endometrial tumors that had been exposed to tamoxifen in the past. CONCLUSIONS: Raloxifene and tamoxifen had similar effects on these mouse models of tamoxifen-naive and tamoxifen-resistant breast and endometrial cancer. Treatment with raloxifene following 5 years of adjuvant tamoxifen may not further decrease breast cancer recurrence and may increase endometrial cancer incidence.     

Endometrial mullerian adenosarcoma after toremifene treatment in breast cancer patients: a case report

Toremifene is an anti-estrogen which has been shown to be effective in the treatment of breast cancer, and is thought to be a less uterotrophic agent than tamoxifen. The risk assessment concerning endometrial cancer has been inconclusive because of its rare use up to the mid-1990s. We report a case of an adenosarcoma, which is a very rare type of uterine malignancy, after toremifene treatment for 5 years in a breast cancer patient. After 1 year of toremifene use, the patient had a benign Mullerian adenofibroma. After an additional 4 years of toremifene treatment, the endometrial polypoid lesion was transformed into a Mullerian adenosarcoma. Although toremifene is a promising anti-estrogenic agent in the treatment of breast cancer patients, clinicians should not neglect the possibility of a uterine malignancy.     

An elderly woman with breast cancer and multiple liver metastasis that responded well to combination therapy of fadrozole and tamoxifen]

Few reports suggest a clinical benefit from combination treatment of fadrozole and tamoxifen for advanced breast cancer in elderly patients. We report the case of an 82-year-old breast cancer patient with multiple liver metastasis. After mastectomy, combination treatment of fadrozole and tamoxifen was added. Two months after the start of this treatment, there was a remarkable reduction in the size of metastatic lesions that continued over 6 months. CT examination revealed the largest lesion was reduced from 8.0 cm to 5.0 cm in largest diameter. The other two lesions were reduced from 3.0 cm to 2.0 cm. The reduction rate was 36%, indicating PR in the Response Evaluation Criteria in Solid Tumors (RECIST). The tumor marker CEA was remarkably reduced from 318 to 85 (ng/ml), and CA15-3 was reduced from 430 to 150 (U/ml). Tumor marker reduction continued over the 6 months corresponding to CT findings. No adverse effect was experienced. This combination therapy was useful and safe against metastatic breast cancer in a patient over 80 years of age.     

Parathyroid hormone-related protein-secreting uterine endometrioid adenocarcinoma

The diagnosis of parathyroid hormone-related protein (PTHrP)-secreting metastatic uterine endometrioid cancer was made in a 32-year-old Japanese woman with humoral hypercalcemia of malignancy. The primary endometrial cancer had been removed, and the tumor was diagnosed as Grade 1 endometrioid adenocarcinoma with shallow myometrial invasion. Salvage chemotherapy (paclitaxel and calboplatin) was started from 5 months after surgery when recurrent tumors were detected in the peritoneum and liver. Despite the salvage chemotherapy, the tumor progressed and hypercalcemia became evident with elevated PTHrP whereas no bone metastasis was identified. To the best of our knowledge, this is the first reported case of hypercalcemia due to PTHrP secretion in uterine endometrioid adenocarcinoma.     

Endometrial Carcinoma in Tamoxifen-Treated Breast Cancer Patients

Summary

Tamoxifen is an important agent for the treatment of breast cancer. Occasionally the drug, which is an antiestrogen, has agonistic estrogenic activity. The authors describe three new cases of endometrial carcinoma developing in breast cancer patients taking tamoxifen and stress the necessity of carefully monitoring the uterine cavity under tamoxifen treatment.     

Tamoxifen DNA damage detected in human endometrium using accelerator mass spectrometry

This study was aimed to establish whether tamoxifen binds irreversibly to uterine DNA when given to women. Patients were given a single therapeutic dose of [(14)C]tamoxifen citrate orally (20 mg, 0.37 or 1.85 MBq) approximately 18 h prior to hysterectomy or breast surgery. Nonmalignant uterine tissue was separated into myometrium and endometrium. DNA and protein were isolated and bound radiolabel determined by the sensitive technique of accelerator mass spectrometry. Levels of irreversible DNA binding of tamoxifen in the endometrium of treated patients were 237 +/- 77 adducts/10(12) nucleotides (mean +/- SE, n = 10). In myometrial tissues, a similar extent of DNA binding was detected (492 +/- 112 adducts/10(12) nucleotides). Binding of tamoxifen to endometrial and myometrial proteins was 10 +/- 3 and 20 +/- 4 fmol/mg, respectively. In breast tissue, sufficient DNA could not be extracted but protein binding was an order of magnitude higher than that seen with endometrial proteins (358 +/- 81 fmol/mg). These results demonstrate that after oral administration, tamoxifen forms adducts in human uterine DNA but at low numbers relative to those previously reported in women after long-term tamoxifen treatment where levels, when detected, ranged from 15000 to 130000 adducts/10(12) nucleotides. Our findings support the hypothesis that the low level of DNA adducts in human uterus is unlikely to be involved with endometrial cancer development.     

Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy

Preclinical models and clinical studies have shown that aromatase inhibitors (AIs) are powerful inhibitors of estrogen synthesis and significantly suppress estrogen in vivo. For more than 20 years, standard first-line treatment for postmenopausal women with metastatic breast cancer has been the antiestrogen tamoxifen, a selective estrogen receptor modulator (SERM) with differential effects on breast, endometrial, bone, and vascular tissues. The estrogenic activity of tamoxifen is associated with deleterious clinical side effects, including vaginal bleeding, endometrial cancer, and thromboembolism. AIs are established second-line treatments in patients who progress with tamoxifen. Compared with progestins, such as megestrol acetate, or the earlier AIs aminoglutethimide and fadrozole, the new AIs, including exemestane, anastrozole, and letrozole, have increased efficacy and clinical benefit and cause fewer side effects in patients with metastatic breast cancer. Letrozole and anastrozole are approved first-line therapy for patients with metastatic breast cancer and as second-line treatment after tamoxifen failure. Studies in the intratumoral aromatase xenograft preclinical model have shown better responses with AIs than with antiestrogens in first-line therapy, and these data are consistent with the results from clinical trials. This model is now being used to assess whether combined or sequential administration of AIs with other agents may provide additional benefit.     

Effects of Tamoxifen on the Cervix and Uterus in Women with Breast Cancer: Experience with Iranian Patients and a Literature Review

Objective: Invasive breast cancer is the most common malignancy in women. Due to the declining mortalityrate that is partly attributable to the use of screening mammography and effective adjuvant therapy, morewomen survive their breast cancers. The aim of this study was to evaluate the effects of tamoxifen on the genitaltract with particular attention to the uterus and cervix. Methods: We investigated the relationship betweentamoxifen and cervical or uterine cancer in Iran, reviewing all the studies performed by the Vali-Asr GynecologyOncology Clinic in Tehran. In addition, the available data on Medline from 1980 until 2009 were reviewed.Results: A total of 182 articles showed associations with gynecologic malignancies. Although as many as 121refered to links between the drug and endometrial abnormalities (polyps or cancers), 55 articles studied therelationship with changes of pap smears, four of which indicated isolated cervical metastasis followed tamoxifenuse in patients with breast cancer. Conclusion: In spite of the significant relationship between tamoxifen andendometrial cancers, cervix is rarely involved in breast cancer patients. However, vaginal bleeding or abnormalvaginal discharge has been reported in all cases before the diagnosis was made. To rule out genital tract malignancy,it is necessary, therefore, to have an annual pelvic exam, pap smear and early endometrial with endocervicalcurettage for tamoxifen users following a breast cancer in those with abnormal uterine bleeding or persistentvaginal discharge.     

The tamoxifen dilemma.

The anti-oestrogen tamoxifen is widely used for adjuvant therapy in the treatment of women with breast cancer and has a low incidence of serious side-effects. It could also play a role as a breast cancer chemopreventive agent. However, epidemiological studies in both tamoxifen-treated breast cancer patients and in healthy women have shown that treatment results in a small increase in the incidence of endometrial cancers. While the use of tamoxifen in breast cancer patients is clearly justified, the situation for its use as a chemopreventive agent in healthy women is not so clear cut. Reasons for caution come from studies in rats that show that tamoxifen is a genotoxic mutagenic liver carcinogen. Initiation of tumours in the rat is the result of metabolic activation of tamoxifen by CYP enzymes to an electrophile(s) that binds irreversibly to DNA. This is not related to the oestrogen receptor status of the tissue. The extent of DNA damage, detected by 32P-post-labelling or accelerator mass spectrometry, is dependent both on the dose and the length of exposure. Studies have been carried out to see if such binding occurs in the uterine endometrium from tamoxifen-treated women. Results are presently inconclusive, but if such irreversible DNA binding occurs, it is at very low levels. Based on a mechanistic understanding of tamoxifen-induced liver carcinogenesis in the rat, it seems that in humans hepatic DNA damage will be close to the limit of detection by 32P-post-labelling and liver cancer will not be a significant carcinogenic risk. We cannot be certain of the mode of action of tamoxifen that results in the increase in endometrial cancers in treated women but it seems unlikely that this will be associated with a classical genotoxic mechanism.     

Risk of endometrial hyperplasia and carcinoma in breast cancer patients receiving adjuvant tamoxifen

The antiestrogen drug tamoxifen, which is widely used in adjuvant hormone therapy of breast cancer, presents certain risk of causing hyperplasia and endometrial carcinoma. Our clinical data on 1,969 breast cancer patients (stage I-III) (tamoxifen--947; control--1,022) showed a double rise in endometrial carcinoma risk in cases receiving hormone therapy. Endometrial carcinoma incidence in tamoxifen-treated patients was 3% while in the untreated ones--1.6% (p < 0.05). According to the endometrial tissue study in 439 breast cancer patients, proliferative effect of tamoxifen in the form of endometrial hyperplasia was 5--6 times in tamoxifen users. Meanwhile, endometrial carcinoma and hyperplasia risk increased during a much longer exposure to tamoxifen and in combination with such factors as obesity, diabetes mellitus, uterine myoma and estrogen-type colpocytological response. Hence, breast cancer patients need to undergo dynamic follow-up of the endometrium including ultrasonic examination of the small-pelvis organs and cytological study of ecto- and endocervical smears and endometrial aspirates.     

Vascular endothelial growth factor reduces tamoxifen efficacy and promotes metastatic colonization and desmoplasia in breast tumors

Clinical studies have shown that decreased tamoxifen effectiveness correlates with elevated levels of vascular endothelial growth factor (VEGF)-A(165) in biopsy samples of breast cancers. To investigate the mechanisms underlying tamoxifen resistance and metastasis, we engineered the estrogen receptor (ER)-positive MCF-7 human breast cancer cell line to express VEGF to clinically relevant levels in a doxycycline-regulated manner. Induction of VEGF expression in orthotopically implanted xenografts that were initially tamoxifen responsive and noninvasive resulted in tamoxifen-resistant tumor growth and metastasis to the lungs. Lung metastases were also observed in a VEGF-dependent manner following tail vein injection of tumor cells. At both primary and metastatic sites, VEGF-overexpressing tumors exhibited extensive fibroblastic stromal content, a clinical feature called desmoplasia. VEGF-induced metastatic colonies were surrounded by densely packed stromal cells before detectable angiogenesis, suggesting that VEGF is involved in the initiation of desmoplasia. Because expression of VEGF receptors R1 and R2 was undetectable in these tumor cells, the observed VEGF effects on reduction of tamoxifen efficacy and metastatic colonization are most likely mediated by paracrine signaling that enhances tumor/stromal cell interactions and increases the level of desmoplasia. This study reveals new roles for VEGF in breast cancer progression and suggests that combination of antiestrogens and VEGF inhibitors may prolong tamoxifen sensitivity and prevent metastasis in patients with ER-positive tumors.     

Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries

Introduction

Tamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer.

Methods

We pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status. Breast cancers were diagnosed in 1972 to 2005 with endometrial cancers diagnosed in 1978 to 2006. We used Cox proportional hazards survival analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI).

Results

A total of 1,104 deaths occurred during, on average, 5.8 years following endometrial cancer (32% attributed to breast cancer, 25% to endometrial cancer). Mortality from endometrial cancer increased significantly with unfavorable non-endometrioid morphologies (P < 0.0001), International Federation of Gynaecology and Obstetrics staging system for gynecological malignancy (FIGO) stage (P < 0.0001) and age (P < 0.0001). No overall association was observed between tamoxifen treatment and endometrial cancer mortality (HR = 1.17 (95% CI: (0.89 to 1.55)). Tamoxifen use for at least five years was associated with increased endometrial cancer mortality (HR = 1.59 (1.13 to 2.25)). This association appeared to be due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for five or more years since the association with mortality was no longer significant after adjustment for morphological type and FIGO stage (HR = 1.37 (0.97 to 1.93)). Those patients with endometrioid tumors, who stopped tamoxifen use at least five years before their endometrial cancer diagnosis, had a greater mortality risk from endometrial cancer than endometrioid patients with no tamoxifen exposure (HR = 2.11 (1.13 to 3.94)). The explanation for this latter observation is not apparent.

Conclusions

Patients with endometrial cancer after breast cancer who received tamoxifen treatment for five years for breast cancer have greater endometrial cancer mortality risk than those who did not receive tamoxifen. This can be attributed to non-endometrioid histological subtypes with poorer prognosis among long term tamoxifen users.     

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women

To assess and compare the gynaecological consequences of the use of 2 antioestrogens we examined 167 postmenopausal breast cancer patients before and during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day, n = 83) as an adjuvant treatment of stage II-III breast cancer. Detailed interview concerning menopausal symptoms, pelvic examination including transvaginal sonography (TVS) and collection of endometrial sample were performed at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30 women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine artery was measured before and at 6 and 12 months of treatment. The mean (+/-SD) follow-up time was 2.3 +/- 0.8 years. 35% of the patients complained of vasomotor symptoms before the start of the trial. This rate increased to 60.0% during the first year of the trial, being similar among patients using tamoxifen (57.1%) and toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline, increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial thickness increased from baseline (3.9 +/- 2.7 mm) to 6.8 +/- 4.2 mm at 6 months (P< 0.001), and no difference emerged between the 2 regimens in this regard. Before the start of the antioestrogen regimen, the endometrium was atrophic in 71 (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign endometrial polyps. During the use of antioestrogen altogether 339 endometrial samples were taken (159 in tamoxifen group, 180 in toremifene group). The endometrium was proliferative more often in the tamoxifen group (47.8%) than in the toremifene group (32.2%) (P< 0.0001). 20 patients had a total of 24 polyps (17 in tamoxifen and 9 in toremifene group, P< 0.05) during the use of antioestrogens. One patient in the toremifene group developed endometrial adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the endometrium. Tamoxifen failed to affect the PI in the uterine artery, but toremifene reduced it by 15.0% (P< 0.05) by 12 months. In conclusion, tamoxifen and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen led to the development of premalignant endometrial changes. Our data suggest that so close endometrial surveillance as used in our study may not be mandatory during the first 3 years of use of antioestrogen treatment.     

Preventing breast cancer in high-risk women, 2008

Several large, prospective trials have evaluated tamoxifen compared with placebo for breast cancer risk reduction in women at increased risk for breast cancer. Analysis of the large, prospective breast cancer risk-reduction trials that used tamoxifen estimated that tamoxifen decreased breast cancer incidence by 38% on average and estrogen receptor-positive tumors by 48%. Tamoxifen is known to have several serious side effects, including uterine malignancy, thromboembolic events, cataracts, and menopausal symptoms, that have limited its usefulness in the risk-reduction setting. Raloxifene (Evista) is a benzothiophene selective estrogen-receptor modulator that has antiestrogenic effects on breast and endometrial tissue as well as estrogenic effects that are similar to but distinct from tamoxifen. Among postmenopausal women who are at increased risk for breast cancer, raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer but appears to be less effective than tamoxifen in reducing the risk of in situ breast cancer. Raloxifene causes less benign and malignant uterine changes and fewer thromboembolic events than tamoxifen. Symptomatic side effects are comparable for the two drugs. Raloxifene is more appropriate than tamoxifen for reduction of breast cancer risk among postmenopausal women at increased risk for breast cancer.     

Tamoxifen flare in advanced endometrial carcinoma

Tamoxifen citrate has recently been shown to be effective palliative therapy in advanced endometrial carcinoma. Flare reactions from tamoxifen are well known in treatment of metastatic breast carcinoma and are not an indication for stopping therapy. We report a patient being treated with tamoxifen for advanced endometrial cancer who developed acute abdominal pain as a manifestation of a flare reaction and the significance of this observation.