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PubMed2000

A 12-month comparative study of raloxifene, estrogen, and placebo on the postmenopausal endometrium.

OBJECTIVE: To determine the effects of a selective estrogen receptor modulator, raloxifene, on postmenopausal endometrium. METHODS: Healthy postmenopausal women (n = 415) were randomly assigned to one of the following four groups: 60 or 150 mg/day raloxifene hydrochloride, 0.625 mg/day conjugated equine estrogens, or placebo, and treated for 1 year. Endometrial biopsies were obtained in a blinded fashion at baseline and every 6 months after the ultrasound studies. Transvaginal ultrasound, with uterine size measurements, was done at baseline and at 3-month intervals. Saline-infusion sonohysterography was done at baseline and every 6 months. RESULTS: There were no statistically significant differences in baseline characteristics. Mean endometrial thickness, measured by transvaginal ultrasound, was unchanged from baseline to end point in the placebo and raloxifene groups, whereas in the estrogen group it was significantly thicker by 5.5 mm (P < .001). Mean uterine volume, calculated from transvaginal ultrasound measurements, was higher in the estrogen group only (22 cm3, P < .001). Of the 358 women with paired biopsies, endometrial hyperplasia was present in 2.1%, 0%, and 26.1% of the end-point biopsies in the placebo, raloxifene, and estrogen groups, respectively (P < .001). Proliferative endometrium was present in 2.1% of the end-point biopsies in the placebo group, 1.7% in the combined raloxifene groups, and 39.8% in the estrogen group (P < .001). CONCLUSION: Raloxifene, at 60 or 150 mg/day for 1 year, did not stimulate the postmenopausal endometrium. End-point endometrial thickness, morphology, and uterine volume in the raloxifene groups were similar to those observed at baseline and in the placebo group.

Adult↗
PubMed2006

Effects of raloxifene on circulating prolactin and estradiol levels in premenopausal women at high risk for developing breast cancer.

BACKGROUND: Prolactin is a peptide hormone necessary for normal breast development that may contribute to breast tumorigenesis. Estrogen is a significant positive regulator of prolactin synthesis; therefore, raloxifene, a selective estrogen receptor modulator under study as a breast cancer prevention agent, may modulate both estradiol and prolactin levels by inhibiting estradiol from binding to its receptor. METHODS: Premenopausal women at increased risk for invasive breast cancer participated in a pilot chemoprevention trial and were given 60 mg raloxifene daily for 24 months. Fasting serum samples collected at baseline and after 12 months on drug were used to measure circulating prolactin, estradiol, and sex hormone binding globulin (SHBG) levels. RESULTS: Of the 27 subjects who completed 12 months of raloxifene, 23 had paired prolactin samples, and 20 had paired estradiol and SHBG samples. Prolactin levels did not significantly change with raloxifene treatment, but SHBG levels increased (mean change = 7.3 nmol/L; P = 0.0001; 95% confidence interval, 3.9-10.7). Estradiol (mean change = 42 pg/mL; P = 0.048; 95% confidence interval, 1-84 pg/mL) levels were elevated when comparing 15 of the 20 women with paired estradiol measurements who also had both of these samples taken during the early follicular phase of the menstrual cycle. CONCLUSIONS: This report is the first to examine the long-term effects of raloxifene on prolactin, estradiol, and SHBG levels in premenopausal women who are also at increased risk for developing invasive breast cancer. Raloxifene had no significant effect on prolactin levels but did increase estradiol and SHBG measurements.

Adult↗
PubMed2004

Antiresorptive treatment of postmenopausal osteoporosis: review of randomized clinical studies and rationale for the Evista alendronate comparison (EVA) trial.

Standard pharmacological antiresorptive therapy for the prevention and/or treatment of postmenopausal osteoporosis now consists of four categories of drugs: estrogens, a selective estrogen receptor modulator (SERM), bisphosponates, and calcitonin. All of these drugs have been studied in randomized controlled trials, but meaningful comparisons of the efficacy of drugs have been difficult due to differences in baseline risks for fracture and differences in study design, including calcium and vitamin D supplementation, definition of fracture, and discontinuation rates. The current paper reviews results from pivotal studies of antiresorptive therapies with fracture as a primary endpoint, as well as head-to-head trials comparing these therapies using surrogate markers of fracture risk, and introduces the first head-to-head trial with fracture as a primary endpoint. The Evista Alendronate Comparison (EVA) trial, a multi-center, double-blind, double-dummy, randomized trial with two active treatment arms is currently underway to compare directly the osteoporotic fracture risk reduction efficacy of raloxifene and alendronate in postmenopausal women with osteoporosis as defined by bone mineral density. The results from this trial will permit more informed judgment by practitioners and provider groups concerning the relative clinical utility of these two drugs.

Alendronate↗
PubMed2004

Raloxifene relaxes rat cerebral arteries in vitro and inhibits L-type voltage-sensitive Ca2+ channels.

BACKGROUND AND PURPOSE: Because of their mixed estrogen-agonist and estrogen-antagonist properties, selective estrogen receptor modulators (SERMs) are considered promising substitutes for hormone replacement therapy. Raloxifene and other SERMs confer estrogen-like cardiovascular protective effects but lack the carcinogenic activity of exogenous estrogen. However, little is known about the cerebrovascular action of raloxifene. Therefore, we studied the effects of raloxifene on the mechanisms regulating rat cerebral artery tone. METHODS: Ring segments of the isolated rat posterior communicating cerebral arteries were mounted in a microvessel myograph for measurement of isometric tension. Whole-cell L-type voltage-sensitive Ca2+ currents were recorded using the perforated patch-clamp technique. Raloxifene (0.1 to 10 micromol/L) reduced the contractile responses to U46619, phenylephrine, and endothelin-1 in normal Krebs solution or to CaCl2 in Ca2+-free, high K+-containing solution. Raloxifene-induced relaxation was identical in endothelium-intact and endothelium-denuded rings. ICI 182780 had no effect on raloxifene-induced relaxation. Raloxifene reduced L-type Ca2+ currents with a pD2 of 5.98+/-0.06, close to that (6.44+/-0.09) for raloxifene-induced relaxation of 60 mmol/L K+-contracted rings. CONCLUSIONS: This study demonstrates that raloxifene acutely relaxes rat cerebral arteries largely via an endothelium-independent mechanism, involving inhibition of Ca2+ influx through L-type Ca2+ channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Current pharmacological options for the management of primary hyperparathyroidism.

Drugs for treating primary hyperparathyroidism can be divided into two main groups: (i) antiresorptive drugs that inhibit the increased bone turnover, which can be divided into estrogen-like compounds (estrogen, oral contraceptives and selective estrogen receptor modulators [SERMs]), bisphosphonates and calcitonin; and (ii) drugs that interfere with parathyroid hormone (PTH) secretion (currently only cinacalcet is available). No drugs that interfere with PTH action are currently available. Available studies suggest that all classes of drugs are able to lower serum calcium levels. However, calcitonin does so only temporarily. Estrogen-containing compounds (hormone replacement therapy) may be less attractive because of the potential risk of breast cancer, cardiovascular disease and deep vein thromboembolism. Oral contraceptives have not been shown to be able to prevent fractures in the general population, and no data are available on their effect in women with primary hyperparathyroidism. The only SERM marketed for hyperparathyroidism is raloxifene and this has not been associated with an increased risk of breast cancer and cardiovascular diseases, and has been shown to be able to prevent vertebral fractures in postmenopausal women with osteoporosis. Two small trials suggest that raloxifene may increase bone mineral density (BMD) and decrease serum calcium levels in patients with primary hyperparathyroidism. Bisphosphonates have been shown to decrease serum calcium and increase BMD in patients with primary hyperparathyroidism, but PTH levels may increase. Cinacalcet effectively induces a sustained decrease in serum calcium and PTH for up to 1 year. However, BMD does not seem to increase. No data on hard endpoints such as fractures, kidney stones, cardiovascular disease etc. are available for any of the drugs available for the treatment of primary hyperparathyroidism.

Bone Density↗
PubMed2006

Effects of raloxifene on platelet functions in patients with postmenopausal osteoporosis.

Many studies have addressed the effects of estrogenic compounds on platelet function. Raloxifene is a selective estrogen receptor modulator (SERM), which is currently used for the treatment of postmenopausal osteoporosis. At present, there are no clinical data about the effects of raloxifene on platelet function. The purpose of this study was to determine if raloxifene at therapeutic doses affects platelet function in patients with postmenopausal osteoporosis. The effects of raloxifene on platelet function were investigated using a commercial platelet function analyzer (PFA-100) with collagen epinephrine and collagen adenosine 5'-diphosphate (ADP) cartridges. We studied platelet function of 30 patients with postmenopausal osteoporosis before and 15 days after initiation of raloxifene 60 mg/daily. Closure times did not differ significantly between samples obtained before (117.8 +/- 20.5 s) and after raloxifene therapy (106.5 +/- 25.4 s) in collagen/epinephrine cartridges (P > 0.05). There was also no statistically significant difference in mean closure times with collagen/ADP cartridges at baseline (86.2 +/- 18.5 s) and after raloxifene therapy (84.4 +/- 13.8 s) (P > 0.05). Platelet counts (278.3 +/- 72.9 vs. 262.4 +/- 56.7 109/L, P > 0.05) and mean platelet volumes (8.9 +/- 1 vs. 9.1 +/- 1 fL, P > 0.05) were not different before and after raloxifene therapy. Although estrogen related compounds do affect platelet function, there is suggestive data in our study that raloxifene in therapeutic dose exhibit no effect on platelet function in patients with postmenopausal osteoporosis.

Aged↗
PubMed2001

Raloxifene.

Raloxifene is a selective estrogen receptor modulator, a compound that has estrogen agonist activity at some sites and antagonist activity at others. In investigations in animals and in rigorously conducted trials in humans, raloxifene treatment is associated with a 30%-40% reduction in risk of one or more spine fractures using the 60 mg dose. This reduction in risk is found in women with or without baseline fractures, in women with bone mineral density (BMD) in the lower, middle, or upper third of the low range (all had BMD reduced by more than 2.5 SD) and in women aged less than 65 years, between 65-70 years, and greater than 70 years. A reduction in ankle fractures, but not hip or wrist fractures, was found. Raloxifene treatment also is associated with a 60%-70% reduction in risk for breast cancer and is associated with reduced total and LDL cholesterol, lower fibrinogen, and no rise in triglyceride. Reduced aortic wall cholesterol content is reported in animal studies. These are surrogate endpoints of cardioprotection. There is no evidence that raloxifene reduces the incidence of myocardial or cerebrovascular events. Raloxifene does not induce breast tenderness, endometrial hyperplasia, menstrual bleeding, or endometrial cancer, but may be associated with an increased risk of thromboembolic disease (1/1000 cases per year), leg cramps in 2%-4% of cases and hot flushes in 4%-6% of cases, usually in first 6 months.

Animals↗
PubMed1999

Out-patient hysteroscopy in asymptomatic postmenopausal women.

OBJECTIVE: To determine the prevalence of uterine and endometrial abnormalities in normal postmenopausal women and assess the accuracy of subjective hysteroscopic appearances and endometrial histology following 12 weeks of hormonal treatment. DESIGN: A multicentered randomized double-blind placebo-controlled trial in which the volunteers received conjugated equine estrogen 0.625 mg, selective estrogen receptor modulator (in one of two doses) or placebo. SETTING: Out-patient endoscopy unit in a large teaching hospital. METHODS: Out-patient hysteroscopy and endometrial biopsy. RESULTS: Forty-eight women had a hysteroscopy and endometrial biopsy: eight (16.6%; 95% confidence interval, CI 6-27%) women had intrauterine polyps and 38 (79.2%) women had normal hysteroscopies. Thirty-five women had a repeat endometrial assessment with hysteroscopy and, for the detection of proliferative endometrium (prevalence 22.8%), a sensitivity of 87.5%, a specificity of 74%, a negative predictive value of 95% and a positive predictive value of 50% were observed. There was a good proportion of agreement, 0.77 (95% CI 0.63-0.91), but a kappa score of 0.486 revealed only a moderate level of agreement. The likelihood ratios for proliferative endometrium were: LHR+ = 3.38 (fair), and LHR- = 0.17 (moderate). CONCLUSIONS: Hysteroscopic assessment of the uterine cavity is efficient in the detection of pathological intrauterine lesions, but is only moderately successful in determining physiological changes in the endometrium. This study defines a standard of observational statistics for out-patient hysteroscopy in relation to normal endometrial histology in postmenopausal women who may have been ingesting exogenous estrogens.

Ambulatory Care↗
PubMed2000

[Raloxifene].

Raloxifene belongs to the group of selective estrogen receptor modulators (SERMs). It interacts with both estrogen receptor alpha and beta, but the postreceptor responses differ from those of estrogens. Raloxifene exerts tissue specific responses that differ from estrogens. The drug increases bone mass by 2-3% and inhibits the risk of subsequent vertebral fractures by 30-50%. Raloxifene reduces the risk of breast cancer by 76% after treatment for four years and builds an atrophic endometrium without any bleedings. Furthermore, the risk of endometrial cancer is not increased. The drug exerts positive effects on plasma lipids, but the effects of these changes on subsequent risk of myocardial infarction and cardiovascular death are still unknown. The main side effects are leg cramps, increases in hot flushes and peripheral oedema. Like estrogen, the drug increases the relative risk for venous thrombosis by a factor three.

Breast Neoplasms↗
PubMed2003

Raloxifene analog LY117018 enhances the regeneration of sciatic nerve in ovariectomized female mice.

The aim of this study was to examine the effects of LY117018, a selective estrogen receptor modulator, on peripheral nerve regeneration, using a model of sciatic nerve crush injury in mice. Sciatic functional index, an index of functional recovery, was significantly higher in LY117018 treated mice throughout regeneration. Analysis of semi-thin sections revealed a significant increase in both the total number of regenerating nerve fibers at day 7, and the mean axonal area of myelinated fibers at 7, 14, and 21 days after injury, in LY117018 treated mice. Analysis of axonal transport through retrograde labeling of motor neurons showed that LY117018 increased transport, and ICI 182,780 blocked the effects of LY117018, delineating estrogen receptors as its target. Our study suggests that LY117018 may markedly accelerate peripheral nerve regeneration and functional recovery through activation of estrogen receptors.

Animals↗
PubMed2006

Histopathology and histomorphometry of the urogenital tract in 15-month old male and female rats treated neonatally with SERMs and estrogens.

In this study, two selective estrogen receptor modulators (SERMs), tamoxifen (TAM) and toremifene (TOR) or two estrogens, ethinylestradiol (EE) and diethylstilbestrol (DES) were administered to newborn male and female Sprague-Dawley rats (days 1-5) to investigate the occurrence of developmental abnormalities in the adulthood. The compounds were dosed (s.c.) at an equimolar dose of 24.9 micromol/kg. During the follow-up period, mortality occurred mainly in DES-treated male rats (3/4), associated with obstructive urinary calculi and suppurative renal inflammation in 2/3 rats. Similar lesions were not evident in other groups. At the age of 15 months, the animals were necropsied and organs were collected for histopathology and histomorphometry. Treatment-related abnormalities were restricted to the reproductive organs. Chronic prostatitis and epithelial abnormalities in the vas deferens were observed in all treatment groups. The columnar epithelium of vas deferens showed hyperplasia and development of subepithelial glandular structures resembling epididymal cysts reported in humans exposed in utero to DES. Testicular atrophy was observed especially in estrogen-treated rats. Mainly in SERM-treated female rats, the uterus showed luminal dilation or obstruction, loss of endometrial glands and myometrium disorganization including foci of muscular disruption. TOR-treated female rats showed polyp-like nodules (incidence 4/15) and a high incidence (9/15) of a simple cuboidal epithelium in cervical regions normally occupied by multilayered epithelia. In conclusion, the vas deferens is a main target organ following neonatal administration of SERMs and estrogens. In addition, female rats were significantly more susceptible to SERM treatment than to treatment with estrogens.

Animals↗
PubMed2005

Repercussions of raloxifen, tamoxifen and estrogen on aortic atherosclerotic lesions of female rabbits submitted to ovariectomy and hypercholesterol diet.

BACKGROUND: The role of hormone-replacement therapy in decreasing the risk of cardiovascular disease in women has not been firmly established. Recent studies have shown that the selective estrogen receptor modulators raloxifene, and tamoxifene, posses hypolipidemic and antiatherogenic properties. METHODS AND RESULTS: Forty-three adult female rabbits were submitted to ovariectomy (moment 1). Three weeks after surgical recovery, they were grouped in five groups as follows (moment 2): control group (9)--normal diet; cholesterol group (8)--0.5% cholesterol added to diet; raloxifen group (8); tamoxifen group (9); estrogen group (9)--diet added by 0.5% cholesterol and 60 mg raloxifen, 20 mg tamoxifen or 0.625 mg equine conjugated estrogen. The animals from all groups were sacrificed after 13 weeks (moment 3) and the thoracic and abdominal aortas were studied. We collected digital images of the observed atherosclerotic lesions in the vessel lumen by means of a computerized method. We analyzed serum levels of total cholesterol and fractions (HDL, VLDL, and LDL), as well as triglycerides. Among the animals that received hyper cholesterol diet and medication, we noticed a reduction of the total area of atherosclerotic plaques in the tamoxifen (P < 0.05) or estrogen group (P < 0.05) compared to the cholesterol group. Serum levels of total, LDL- and HDL-cholesterol were higher for the raloxifen, tamoxifen, estrogen, and cholesterol (P = 0.0001). CONCLUSION: Female rabbits treated with a high cholesterol diet associated to tamoxifen or estrogen had a statistically significant reduction in aortic atherosclerotic plaques. Even though there was a significant increase in cholesterol levels, we did not find any correlation between cholesterol levels and degree of aortic atherosclerotic lesion.

Animals↗
PubMed2006

Emerging principles for the development of resistance to antihormonal therapy: implications for the clinical utility of fulvestrant.

We seek to evaluate the clinical consequences of resistance to antihormonal therapy by studying analogous animal xenograft models. Two approaches were taken: (1) MCF-7 tumors were serially transplanted into selective estrogen receptor modulator (SERM)-treated immunocompromised mice to mimic 5 years of SERM treatment. The studies in vivo were designed to replicate the development of acquired resistance to SERMs over years of clinical exposure. (2) MCF-7 cells were cultured long-term under SERM-treated or estrogen withdrawn conditions (to mimic aromatase inhibitors), and then injected into mice to generate endocrine-resistant xenografts. These tumor models have allowed us to define Phase I and Phase II antihormonal resistance according to their responses to E(2) and fulvestrant. Phase I SERM-resistant tumors were growth stimulated in response to estradiol (E(2)), but paradoxically, Phase II SERM and estrogen withdrawn-resistant tumors were growth inhibited by E(2). Fulvestrant did not support growth of Phases I and II SERM-resistant tumors, but did allow growth of Phase II estrogen withdrawn-resistant tumors. Importantly, fulvestrant plus E(2) in Phase II antihormone-resistant tumors reversed the E(2)-induced inhibition and instead resulted in growth stimulation. These data have important clinical implications. Based on these and prior laboratory findings, we propose a clinical strategy for optimal third-line therapy: patients who have responded to and then failed at least two antihormonal treatments may respond favorably to short-term low-dose estrogen due to E(2)-induced apoptosis, followed by treatment with fulvestrant plus an aromatase inhibitor to maintain low tumor burden and avoid a negative interaction between physiologic E(2) and fulvestrant.

Animals↗
PubMed2001

Lack of substantial effects of raloxifene on thyroxine-binding globulin in postmenopausal women: dependency on thyroid status.

Long-term estrogen therapy can modify thyroid hormone kinetics by increasing serum concentration of thyroxine-binding globulin (TBG). Raloxifene is a recently developed selective estrogen receptor modulator (SERM) for the treatment of osteoporosis, which possesses estrogenic and antiestrogenic properties. In a prospective and randomized study, we investigated the effects of raloxifene on TBG levels and on the serum concentrations of free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) in controls and in patients receiving TSH-suppressive doses of levothyroxine (LT4). Twenty-nine postmenopausal osteopenic (n = 14) and osteoporotic (n = 15) women were investigated over a period of 6 months. Group 1 (n = 15) included control patients and group 2 (n = 14) patients receiving TSH-suppressive dose of LT4. All patients were treated with raloxifene hydrochloride, 60 mg/d, for a period of 6 months. Serum basal TBG values were found higher in Group 1 compared to Group 2 (26.2 2 microg/mL vs. 21.4 2.1 microg/ml; p < 0.01). The TBG levels raised slightly in group 1 from 26.2 2 microg/mL to 28.6 3.1 microg/mL; p < 0.05 (in group 2 from 21.4 2.1 microg/mL to 22.2 2.3 microg/mL, not significant) after 3 months of treatment and failed to show any further significant change until the end of the study. Serum concentrations of T4, FT4, T3, and TSH levels changed insignificantly in both groups up to the completion of the study. Moreover, patients remained clinically euthyroid. Our findings may provide evidence that TBG levels, and consequently, thyroid function are not substantially affected by treatment with raloxifene. Additionally, TBG levels may also be influenced by small variations of thyroid function as subclinical hyperthyroidism.

Aged↗
PubMed2005

Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy.

OBJECTIVE: Raloxifene hydrochloride is a selective estrogen receptor modulator that to date has not been shown to cause hypertriglyceridemia in normal, diabetic, or hypertriglyceridemic women. This study was designed to assess the effect of raloxifene on serum triglycerides in postmenopausal women who have a history of increased hypertriglyceridemia with oral estrogen therapy. RESEARCH DESIGN AND METHODS: This was a single-center, uncontrolled, open-label study investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma lipids. The study subjects were 12 postmenopausal women, ages 49-73 years, with a documented history of oral estrogen-induced hypertriglyceridemia (serum triglycerides > or =3.39 mmol/l [> or =300 mg/dl]). RESULTS: At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (>or =11.3 mmol/l [> or =1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL(2) levels (P = 0.013 and 0.03, respectively). CONCLUSIONS: Patients with a previous history of hypertriglyceridemia on oral estrogen therapy should have serum triglyceride levels monitored closely after beginning raloxifene therapy and may even require fibrate therapy before beginning raloxifene.

Aged↗
PubMed2005

[Raloxifene (Evista) in the treatment of postmenopausal osteoporosis--the profile of the patient].

Osteoporosis, breast cancer and cardiovascular diseases are major health problems among postmenopausal women. Several pharmacologic options for treatment of osteoporosis are available, including hormone replacement therapy (HRT), bisphosphonates, calcitonin and selective estrogen receptor modulators. However, longterm HRT is associated with unwanted side effects such as vaginal bleeding and breast cancer and bisphosphonates, besides bone, have no other benefits. Therefore, raloxifene, the first of the second-generation of SERMs represents a significant improvement in the treatment of postmenopausal women. It could have either estrogen agonist (bone) or antagonist (breast) activity according to the type of estrogen-responsive tissue. Raloxifene prevents bone loss, reduces the number of vertebral fractures in women with and without prevalent vertebral fractures, induces reduction of estrogen-receptor positive invasive breast cancer and has potential beneficial effect on cardiovascular diseases in women with high risk. CORE study, that was recently published, confirmed previously observed reduction of invasive breast cancer in women treated with raloxifene (MORE study), while the data on skeletal effects after 8-years treatment with raloxifene will be published in the near future. Further studies (RUTH, STAR) will provide additional information on efficacy and safety of raloxifene.

Female↗
PubMed2002

[Tamoxifen and breast cancer].

Tamoxifen is a selective estrogen receptor modulator (SERM) with pro- and anti-estrogenic properties. Currently it is the most widely used agent for first line treatment against hormone sensitive metastatic breast cancer and the only approved hormonal agent for adjuvant treatment of organ confined breast cancer. Furthermore, its uses have been extended for the treatment of intraductal breast carcinoma patients. In such settings the most worrisome side effect of tamoxifen is its ability to increase the rates of uterine cancers. It has been claimed that most of these cancers are found at an early stage because of vaginal bleeding. Moreover, it has been shown that for most women transvaginal ultrasound is an ineffective screening method for the early detection of uterine carcinomas. It is important, however, to notice that long term tamoxifen treatment can cause metastatic uterine cancer--not only carcinomas but also sarcomas (mainly malignant mixed mesodermal tumors. It should be noted that, at least for the special population of BRCA mutation carriers, transvaginal ultrasound can increase our ability for the earlier discovery of ovarian cancer. Thus, we believe that there is still a place for the use of transvaginal ultrasound in special populations. This is specifically for long term tamoxifen users (more than the usually recommended five years), women with a higher chance of having uterine carcinomas (namely very high body weight, strong family history) and women with a high index of suspicion as carriers of a BRCA mutation. Until new second generation SERMs and aromatase inhibitors are shown to possess better anti-cancer abilities than tamoxifen, this drug will remain in wide use, however, we must not overlook its possible rare side effects.

Antineoplastic Agents, Hormonal↗
PubMed2002

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.

Animals↗