Patients Receiving Tamoxifen Therapy Research Articles

Ovarian Cysts Formation in Patients with Breast Cancer on Tamoxifen Therapy in Iraqi Female

Background: Tamoxifen shows complex hormonal actions, breast cancer that occurs in the premenopausal period treated with tamoxifen created huge quantities of estrogen. Objectives: This study was conducted to determine the prevalence of ovarian cysts formation in tamoxifen treatments by ultra-sonographic examinations. Method: A prospective study was carried out in the Oncology and Nuclear medicine specialist Hospital, Mosul/Iraq. There were 14 premenopausal and 36 postmenopausal patients. The inclusion criteria were patients with breast cancer who had been on tamoxifen therapy. Fifty patients were included during a period of 10 months. The following parameters were assessed by ultrasound, endometrial thickness and ovaries conditions, with clinical parameters, age of patients, weight, and associated symptoms. Results: A total of 50 patients getting tamoxifen management, 14 (28%) of them are premenopausal range their age was between 25 to 44 years, and 36 (72%) postmenopausal range their age was between 45 to 78 years. There’s a correlation between the age group of patients and ovarian changes and cystic formation the ovarian cysts were diagnosed. There’s a relation between increased endometrial thickness and incidence of ovarian cyst in patients receiving tamoxifen therapy and mild relation between increased endometrial thickness and RT ovarian cystic formation in which the p-value of RT ovary = .049. In contrast, the LT ovary shows a relation with p-value = .025, which was significant. Conclusion: Ovarian cysts are common genital tract complications of tamoxifen therapy, which had been developed in this study in about 20% of cases. Ovarian cysts can grow together with premenopausal and postmenopausal patients getting tamoxifen for treated breast cancer.

MicroRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study

BackgroundAround 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. MethodsThis case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. ResultsThere was a significant difference in miR-221 expression (p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) (p = 0.25), had high and low marker of proliferation Ki-67 levels (p = 0.60), were positive and negative for lymphovascular invasion (p = 0.14), and had stage 2 and stage 3 cancer (p = 0.25). ConclusionmiR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance.

Uterine Fibroid in Breast Cancer Patients receiving Tamoxifen Therapy

Abstract
 Objective: Selective estrogen receptor modulators (SERMs) such as tamoxifen play a role in increasing the risk of developing uterine Fibroid.Methods: Case reportCase: Mrs. 47 years old, Para 6, presented with chief complaints of vaginal bleeding since a year ago. The patient was diagnosed with breast carcinoma 4 years ago and has had a right mastectomy followed by 6 cycles of chemotherapy which is then continued with tamoxifen treatment for 4 years, USG examination revealed uterine myoma to which we performed bilateral salphingoophorectomy hysterectomy, with anatomic pathology results of a uterine Fibroid and chronic endometritis.Conclusion: Selective estrogen receptor modulators (SERMs) such as tamoxifen exhibit antagonistic reactions in breast tissue which makes it appropriate to be used in the treatment of breast cancer. However, they can also be potentially agonistic on estrogen receptors in the uterus, which can cause the growth of uterine Fibroid. Nevertheless, the benefits of adjuvant tamoxifen for breast cancer outweighs its potential for developing uterine Fibroid and endometrial carcinoma, because metastatic breast cancer will always be fatal, whereas uterine myoma and endometrial cancer caused by the effects of tamoxifen can be prevented by regular evaluation and total hysterectomy.Keywords: breast cancer,tamoxifen, uterine fibroid,
 
 Abstrak
 Tujuan: Selektif estrogen reseptor modulator (SERMs) seperti tamoksifen berperan dalam meningkatkan risiko mengembangkan mioma uteri. Metode: Laporan KasusKasus: Ny 47 Thn Para 6, datang dengan keluhan perdarahan dari jalan lahir yang dirasakan ibu selama 1 tahun ini, pasien telah menderita kanker payudara 4 tahun yang lalu dan telah dilakukan mastektomi mammae dextra dilanjutkan kemoterapi 6 siklus kemudian dilanjutkan dengan pengobatan tamoksifen selama 4 tahun ini, dari pemeriksaan USG didapatkan adanya mioma uteri kemudian dilanjutkan dengan tindakan histerektomi salphingooforektomi bilateral, dengan hasil patologi anatomi suatu mioma uteri dan endometritis kronis.Kesimpulan: Selektif estrogen reseptor modulator (SERMs) seperti tamoksifen merupakan reaksi antagonis reseptor estrogen pada jaringan payudara yang digunakan dalam pengobatan kanker payudara, tetapi dapat berpotensi agonis pada reseptor estrogen pada uterus sehingga dapat menyebabkan pertumbuhan mioma uteri. Tetapi penggunaan tamoksifen ajuvan untuk kanker payudara lebih bermanfaat dibandingkan dengan potensinya untuk mengembangkan mioma uteri dan karsinoma endometrium, karena kanker payudara metastatik akan selalu berakibat fatal, sedangkan mioma uteri dan kanker endometrium yang ditimbulkan oleh efek tamoksifen dapat dicegah dengan evaluasi teratur dan dilakukan tindakan total histerektom.Kata kunci: kanker payudara, mioma uteri, tamoksifen

Sonographic Study of Female Pelvic Organs in Breast Cancer Patients Taking Tamoxifen: Clinical Correlation

Background: As most of breast cancer patients are treated with Tamoxifen, different effects of this drug in patients should be evaluated since no such study is carried out in Bangladesh till date.
 Objective: The purpose of the present study was to evaluate sonographic changes of female genital organs in breast cancer patients treated with Tamoxifen and to correlate these changes with duration of Tamoxifen treatment and gynecological symptoms.
 Methodology: This randomized double-blind clinical trial was carried out in Delta Medical College Hospital, Dhaka, Bangladesh from May 2017 to April 2018 for a period of one (1) year. The participants were breast cancer patients which were divided into three groups named as group I patients. The patients of these group were on Tamoxifen therapy. The patients of group II were without Tamoxifen therapy. The patients of group III had completed Tamoxifen therapy. All participants underwent ultrasonography.
 Results: Patients receiving Tamoxifen therapy had significantly more thickened endometrium compared to other groups (26.6% in group I, 5% in group II and3% in group III). Similarly, abnormal sonographic findings and mean uterine volume were higher in group I compared to other two groups. Endometrial thickness and uterine volume showed significant positive correlation with duration of Tamoxifen therapy (p <0.0001). The endometrial thickness and uterine volume greatly increased after two years of Tamoxifen therapy while it was reverse in group III. Gynecological symptoms had no significant relations with sonographic abnormalities and thickened endometrium.
 Conclusion: Tamoxifen therapy is associated with increased endometrial thickness, uterine volume and abnormal sonographic findings, compared to patients without Tamoxifen or completing Tamoxifen therapy.
 Journal of Current and Advance Medical Research 2020;7(1): 17-23

Retinal structural changes in patients receiving tamoxifen therapy by spectral-domain optical coherence tomography

Purpose: To evaluate choroidal thickness, ganglion cell complex (GCC) and photoreceptor outer segment (PROS) length were measured in patients with breast cancer undergoing tamoxifen therapy, using spectral-domain optical coherence tomography (SD-OCT); results were compared with those for normal eyes.Materials and methods: Forty-four patients with breast cancer, undergoing tamoxifen therapy, and 41 healthy controls were included in this prospective, comparative study. All participants underwent a complete ophthalmologic evaluation and SD-OCT. Subfoveal, nasal (nasal distance to fovea 500, 1000, 1500 μm), and temporal (temporal distance to fovea 500, 1000, 1500 μm) choroidal thickness measurements were performed using the enhanced depth imaging mode of SD-OCT. Using an Early Treatment Diagnostic Retinopathy Study (ETDRS) circle at the macular level, the automated retinal segmentation software was applied to determine the thickness of the GCC. PROS length was determined manually, as the distance from the inner surface of the ellipsoid zone to the inner surface of retina pigment epithelium.Results: The mean choroidal thickness was statistically greater in the tamoxifen group than controls in all quadrants (p < 0.001 for all quadrants). Of all tamoxifen users (44 eyes of 44 patients), 33 eyes (75%) had uncomplicated pachychoroid (UCP). Pachychoroid pigment epitheliopathy (PPE) was detected in five tamoxifen-group patients (11.3%). Patients with PPE in one eye had UCP in the fellow eye. Central serous chorioretinopathy findings were observed in one patient. Tamoxifen users had statistically lower GCC thickness in all inner rings of the ETDRS inlay and in the nasal outer ring only (p = 0.027, 0.002, 0.002, 0.001, and 0.030, respectively). No statistically significant difference in mean subfoveal PROS length was found between the groups.Conclusions: SD-OCT provides valuable information for identifying structural changes and evaluating ocular findings in patients receiving tamoxifen therapy. Increased choroidal thickness, PPE and thinning GCC were detected in tamoxifen users. These OCT findings may be an early indicator of retinal toxicity for patients undergoing tamoxifen therapy in the follow-up period.

Abstract 2295: Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer

Abstract Background: The androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes. Despite the high frequency of AR expression in breast cancer its appraisal remains controversial because its role is complex, dependent on the hormonal milieu. The aim of the current study was to investigate the frequency of AR and ER positive CETCs in breast cancer patients. Material and Methods: The number of vital CETCs was determined from blood of 66 patients suffering from breast cancer and the expression of AR and ER on these cells was investigated using the maintrac method. Results: Numbers of CETCs/ml blood were significantly higher in patients with advanced disease as compared to patients with early stage disease. The fraction of AR positive CETCs was significantly higher than the fraction of ER positive CETCs (90% vs. 50%; p&amp;lt;0.001). Patients with positive lymph nodes had less AR positive CETCs as compared to patients with negative lymph node status. The AR:ER ratio was higher in patients receiving tamoxifen therapy as compared to patients without tamoxifen therapy whereas treatment with aromatase inhibitor had no influence on AR:ER ratio. Conclusions: The ratio of AR to ER positive CETCs, obviously, is influenced by endocrine therapy, more specifically therapy with tamoxifen. Since AR expression seems to be responsible to resistance to endocrine therapy this may provide a new biomarker to select patients who might benefit from combination treatment of ER and AR inhibitors. Note: This abstract was not presented at the meeting. Citation Format: Monika Pizon, Dorothea Schott, Daniel Lux, Ulrich Pachmann, Katharina Pachmann. Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2295.

Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer

BackgroundThe androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes. Despite the high frequency of AR expression in breast cancer its appraisal remains controversial because its role is complex, dependent on the hormonal milieu. The aim of the current study was to investigate the frequency of AR and ER positive CETCs in breast cancer patients.MethodsThe number of vital CETCs was determined from blood of 66 patients suffering from breast cancer and the expression of AR and ER on these cells was investigated using the maintrac method.ResultsNumbers of CETCs/mL blood were significantly higher in patients with advanced disease as compared to patients with early stage disease. The fraction of AR positive CETCs was significantly higher than the fraction of ER positive CETCs (90% vs. 50%; P < 0.001). Patients with positive lymph nodes had less AR positive CETCs as compared to patients with negative lymph node status. The AR:ER ratio was higher in patients receiving tamoxifen therapy as compared to patients without tamoxifen therapy whereas treatment with aromatase inhibitor had no influence on AR:ER ratio.ConclusionsThe ratio of AR to ER positive CETCs, obviously, is influenced by endocrine therapy, more specifically therapy with tamoxifen. Since AR expression seems to be one of the possible mechanism of resistance to endocrine therapy this may provide a new biomarker to select patients who might benefit from combination treatment of ER and AR inhibitors.

Abstract P3-02-03: Accurate and reliable automated breast density measurements with no ionizing radiation using fat-water decomposition MRI

Abstract Objective Breast density(BD) is a measure of the distribution of variable tissue types within the breast and higher BD has been shown to positively correlate with breast cancer risk. As such, the accurate measurement of BD has become a priority for risk assessment and for evaluating the effects of prevention strategies aimed at reducing BD. Mammography(MG) is the most common method of BD determination but is limited by the exposure to ionizing radiation, particularly for studies requiring repeated measures. BD derived from fat-water decomposition magnetic resonance imaging(FWMRI-BD) has been proposed as an alternative, safe, and quantitative method for BD. To optimize its use, we developed a new FWMRI-BD that is automated, more accurate and reliable. In this study, we compare our automated method to digital MG and a previous reported algorithm for MRI derived BD. Methods From a completed prevention trial, 42 pre- and post-menopausal patients receiving tamoxifen therapy for early stage breast cancer or as primary chemoprevention were identified. Patients had undergone prior digital MG within 6 months from the date of MRI scan and MG-BD was calculated using a well-established method(Cumulus). MRI scans were performed on a 1.5T GE Signa NV-CV/i scanner using an axial radial IDEAL-GRASE sequence to generate quantitative fat fraction maps of the entire breast. Total acquisition time was &amp;lt; 5 min and automated breast segmentation was applied to all scans. Only the contralateral, unaffected breast was analyzed. Pearson correlation analysis compared BD as measured by MG(range 0-100%) and FWMRI based methods. BD by FWMRI was initially calculated as the ratio of breast voxels with&amp;lt;80% apparent fat fraction(Fra80). Fra80 had been previously shown by our group to correlate with MG-BD(Spearman ρ=0.86, p&amp;lt;0.001). Here, BD was calculated using a new algorithm(FraG+W) that accounts for the total amount of fibroglandular tissue and water content in the breast after correction for fat-water signal intensity bias and fat-water signal shine-through. Reliability of FWMRI measurements was tested in 24 repeated scans from 9 patients and evaluated using intra-class correlation(ICC) analysis. Results Table 1 shows the correlation and reliability analysis results between MG-BD and FWMRI-BD. Both FWMRI-BD measures(Fra80 and FraG+W) were strongly correlated with MG-BD. More importantly, they exhibit superior test-retest reliability(ICC&amp;gt;0.98) compared to MG-BD values from the literature(reported ICC range 0.91-0.95). FraG+W showed improvement over Fra80 in all measures tested including correlation to MG-BD, dynamic range, standard errors and ICC. Table 1. Accuracy and Reliability of the FWMRI-BD measuresFWMRI-BDFra80FraG+WPearson correlation coefficient* with MG-BDR=0.86R=0.94Test-retest reliabilitystandard error0.02300.0134dynamic range0.0902 – 0.65370.0736 – 0.6588standard error/ dynamic range4.1%2.3%ICC [95% confidence interval]0.985 [0.966,0.993]0.990 [0.976,0.995]* All P-values &amp;lt; 1e-10 Conclusion The refined and automated FWMRI-BD that quantifies the entire fibroglandular and water content of the breast(FraG+W) strongly correlates with MG-BD and is more accurate and reliable than previous FWMRI-BD method. Acknowledgement NIH grants CA149417, CA161534. Citation Format: Ding J, Thompson PA, Gao Y, Marron MT, Wertheim BC, Altbach MI, Galons J-P, Roe DJ, Wang F, Maskarinec G, Thomson CA, Stopeck A, Huang C. Accurate and reliable automated breast density measurements with no ionizing radiation using fat-water decomposition MRI [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-02-03.

Aggressive bladder leiomyosarcoma in a patient receiving tamoxifen therapy

Aggressive bladder leiomyosarcoma in a patient receiving tamoxifen therapy

The Eyes Have It! Tamoxifen Maculopathy Revisited: A Case Report

To report on tamoxifen crystalline maculopathy in an 80-year-old patient and to review the ocular side effects of oral tamoxifen. We report a case of an 80-year-old female patient who presented to our ophthalmic institute with painless gradual progressive diminution of vision in both eyes. She had a history of surgery for breast cancer after which she had been treated with oral tamoxifen citrate for 2 years before presentation. Our patient had profound visual impairment in both eyes. The anterior segments were found to be normal; in particular, the corneas were clear; the intraocular pressures in both eyes were 12 mm Hg. The perimacular region in both eyes showed deposits of multiple, fine crystalline material. Color vision was found to be impaired in both eyes and optical coherence tomography (OCT) confirmed the diagnosis of tamoxifen-induced maculopathy. Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of hormone-responsive breast cancer. Ocular complications are rare with tamoxifen therapy and include cataract, vortex keratopathy, optic neuritis, and retinopathy. Crystalline maculopathy is one of the rare side effects of long-term tamoxifen use, which can be detected by noninvasive diagnostic tools such as OCT. Our patient is the oldest such patient reported in literature. Patients receiving tamoxifen therapy must be informed about the potential side-effects, and the need for serial ophthalmic examination to detect early signs of toxicity.

Should CYP2D6 inhibitors be administered in conjunction with tamoxifen?

Tamoxifen has been used for the treatment or prevention of recurrence in patients with estrogen receptor-positive breast cancers. Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, ‘endoxifen’, some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. However, there are some discrepant reports for the association between CYP2D6 genotype and clinical outcomes of tamoxifen therapy, probably because of the heterogeneity in sample collection or analysis, including differences in regimen of tamoxifen treatment. A review of published reports regarding the effects of selective serotonin reuptake inhibitors on the pharmacokinetics and/or efficacy of tamoxifen found that concurrent use of strong CYP2D6 inhibitors, especially paroxetine, and possibly others, should be avoided in patients receiving tamoxifen therapy, but there has not been enough evidence for the effects of weak or moderate inhibitors.

CITED2 and NCOR2 in anti-oestrogen resistance and progression of breast cancer

Background:Endocrine therapies of breast cancer are effective but ultimately fail because of the development of treatment resistance. We have previously revealed several genes leading to tamoxifen resistance in vitro by retroviral insertion mutagenesis. To understand the manner in which these genes yield tamoxifen resistance, their effects on global gene expression were studied and those genes resulting in a distinct gene expression profile were further investigated for their clinical relevance.Methods:Gene expression profiles of 69 human breast cancer cell lines that were made tamoxifen resistant through retroviral insertion mutagenesis were obtained using oligonucleotide arrays and analysed with bioinformatic tools. mRNA levels of NCOR2 and CITED2 in oestrogen receptor-positive breast tumours were determined by quantitative RT–PCR. mRNA levels were evaluated for association with metastasis-free survival (MFS) in 620 patients with lymph node-negative primary breast cancer who did not receive systemic adjuvant therapy, and with clinical benefit in 296 patients receiving tamoxifen therapy for recurrent breast cancer.Results:mRNA expression profiles of most tamoxifen-resistant cell lines were strikingly similar, except for the subgroups of cell lines in which NCOR2 or CITED2 were targeted by the retrovirus. Both NCOR2 and CITED2 mRNA levels were associated with MFS, that is, tumour aggressiveness, independently of traditional prognostic factors. In addition, high CITED2 mRNA levels were predictive for a clinical benefit from first-line tamoxifen treatment in patients with advanced disease.Conclusions:Most retrovirally targeted genes yielding tamoxifen resistance in our cell lines do not impose a distinctive expression profile, suggesting that their causative role in cell growth may be accomplished by post-transcriptional processes. The associations of NCOR2 and CITED2 with outcome in oestrogen receptor-positive breast cancer patients underscore the clinical relevance of functional genetic screens to better understand disease progression, which may ultimately lead to the development of improved treatment options.

Endoxifen, but not 4-hydroxytamoxifen, degrades the estrogen receptor in breast cancer cells: a differential mechanism of action potentially explaining CYP2D6 effect.

Abstract Abstract #19 Background: Tamoxifen (TAM) is a standard endocrine therapy for the treatment of women with estrogen receptor (ER) positive breast cancer. TAM is activated by the cytochrome P450 2D6 enzyme system into two potent and active metabolites, 4-hydroxytamoxifen (4HT) and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen). While human concentrations of 4HT are negligible and vary little in plasma (5-10 nM), endoxifen concentrations vary widely (10-180 nm), and women with genetically impaired CYP2D6 metabolism have significantly reduced endoxifen levels and a higher risk of breast cancer recurrence. Despite these observations, endoxifen's contribution to tamoxifen's overall drug effectiveness is uncertain.&amp;#x2028; Methods: Using cells endogenously expressing ERa (MCF7, T47D) and cells stably transfected with ERa (Hs578T and U2OS), we examined the relative effects of TAM and its primary metabolites on ERa protein levels by western blotting, ERa transcriptional activity by luciferase reporter assays and real-time RT-PCR, and on ER positive breast cancer cell growth through the use of proliferation assays.&amp;#x2028; Results: We have discovered that endoxifen induces ERa protein turnover through proteasomal degradation similar to that of ICI in a concentration and time-dependent manner. These findings are in stark contrast to TAM, N-desmethyl-tamoxifen (NDT) and 4HT, which stabilize the ER. Optimal degradation occurs only at endoxifen concentrations observed in human CYP2D6 extensive metabolizers (&amp;gt; 40 nM) and persists even in the presence of TAM (300 nM), 4HT (7 nM), and NDT (700 nM) at concentrations observed in patients receiving tamoxifen therapy. In contrast, reducing endoxifen concentrations to those observed in a CYP2D6 poor metabolizer (20 nM), without altering TAM, 4HT, and NDT, results in ER stabilization. High endoxifen concentrations (100-1000 nM) completely block estrogen (E2)-induced ER transcriptional activity even in the presence of TAM, 4HT, and NDT, while low endoxifen concentrations (20-40 nM) do not. Further, low concentrations of endoxifen (20 nM) do not significantly alter E2-induced cell proliferation; however, high concentrations of endoxifen (100-1000 nM) completely block this process. Discussion: Our data demonstrate that endoxifen is a potent anti-estrogen that targets ERa for proteasomal degradation, blocks ERa transcriptional activity and inhibits E2-induced breast cancer cell proliferation. Importantly, these effects of endoxifen are observed at concentrations found in CYP2D6 extensive metabolizers and are maintained even in the presence of TAM, 4HT and NDT. These studies suggest that endoxifen may be the primary metabolite responsible for tamoxifen's effectiveness in the treatment of ER positive breast cancer and provide the impetus to evaluate whether TAM-related side-effects, such as thrombo-embolism and endometrial hyperplasia/carcinoma, are inversely associated with a patient's ability to metabolically activate tamoxifen. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 19.

Optimizing the antihormonal treatment and prevention of breast cancer

The incidence of breast cancer is rising throughout the world. Breast cancer is slowly becoming more prevalent in countries which previously had low rates of cancer as well as becoming a leading cause of cancer death in some countries. Fortunately, a large number of these tumors are estrogen receptor (ER) positive and respond to anti-hormonal adjuvant therapy which until recently has been 5 years of tamoxifen treatment. Unfortunately, a significant number of patients develop recurrent cancers and the recurrent tumors are resistant to tamoxifen treatment. In addition, because of tamoxifen's selective estrogenic actions, there have been reports of venous thrombosis, endometrial cancer, and strokes in patients receiving tamoxifen therapy. Thus, there are other novel therapies such as aromatase inhibitors that block estrogen production in postmenopausal women or fulvestrant that destroys the estrogen receptor. This paper will summarize the therapeutic options for anti-hormonal therapy, the role of anti-hormonal agents in advanced breast cancer, and adjuvant therapy and the current status of chemoprevention with selective ER modulators.

Two-Gene Expression Ratio Predicts Recurrence and Survival in Breast Cancer Patients Receiving Tamoxifen Therapy

Two-Gene Expression Ratio Predicts Recurrence and Survival in Breast Cancer Patients Receiving Tamoxifen Therapy

Myxoid Leiomyosarcoma of the Uterus in a Patient Receiving Tamoxifen Therapy: A Case Report

In this paper, we present a case of myxoid leiomyosarcoma development in a patient receiving tamoxifen for 3 years because of breast cancer. The myxoid leiomyosarcoma should be included in the differential diagnosis of any uterine tumor with a predominantly myxomatous composition. A review of the literature indicates that tamoxifen may increase not only the risk for endometrial cancer but also for uterine sarcoma, suggesting vigilance for uterine cancer in women who are being treated with this drug.

Controversias en la prevención de patología endometrial en mujeres en tratamiento con tamoxifeno

Objective Numerous protocols have been published on the management and follow-up of patients receiving tamoxifen therapy to enable early diagnosis of endometrial malignancy. The ideal protocol is controversial. This study presents the protocol followed in our department, based on our experience and the small amount of evidence available. Patients and methods We describe the activity in the gynecology service between 1996 and 1999. A total of 247 hysteroscopies were performed in 188 patients with breast cancer receiving tamoxifen therapy. Results The most frequent reasons for hysteroscopy were ultrasound (36.8%) and surveillance in asymptomatic women receiving tamoxifen (44.9%). There were only three cases of endometrial cancer. Endometrial thickness measured by ultrasound was 6-10 mm in 28.5% of the patients and was more than 11 mm in 64.5%. Conclusions Close clinical follow-up and hysteroscopy with biopsy when symptoms are present (metrorrhagia, spotting, staining or leukorrhea) are required. Transvaginal ultrasonography is advisable before starting treatment and hysteroscopy should be performed when endometrial disease is suspected. We encourage annual hysteroscopy in high-risk women. A randomized trial of women undergoing ultrasonographic monitoring and hysteroscopy when disease is suspected versus those undergoing clinical follow-up and hysteroscopy when symptoms are present should be performed.

Unusual occurrence of left ventricular thrombus with normal left ventricular wall motion in a patient receiving tamoxifen therapy

Case Report: Unusual occurrence of left ventricular thrombus with normal left ventricular wall motion in a patient receiving tamoxifen therapy -

Controversy about uterine effects and safety of SERMs: the saga continues.

From the perspective of endometrial safety, there has been great controversy about what special management, if any, tamoxifen-treated patients should undergo. Periodic blind endometrial sampling or transvaginal ultrasound has been advocated by some. Because of the problems associated with either of these techniques alone, we recommended an approach that used transvaginal ultrasound and then proceeded to sonohysterography when the endometrial echo on transvaginal ultrasound was not reliably thin and distinct. The American College of Obstetricians and Gynecologists (ACOG), in its committee opinion, stated that patients receiving tamoxifen therapy should only have an annual pelvic exam with pap smear if they remain asymptomatic. Newer data suggest, however, that there are high- and low-risk groups that can be identified by pretreatment screening. Before tamoxifen therapy, 17% of patients have polyps. These patients have 17 times the incidence of atypical hyperplasia than those whose uterus was negative before tamoxifen therapy. Such findings call into question the validity of the only study of raloxifene where uterine safety was the primary endpoint. In that study, any woman with baseline endometrial findings other than pristinely negative (i.e., low risk) was excluded. However, other raloxifene studies without pretreatment screening show relative risk (RR) = 0.8 (95% CI = 0.2, 2.7) for endometrial carcinoma. This compares with the women over 50 years of age in the Breast Cancer Prevention Trial (National Surgical Adjuvant Breast and Bowel Project P-1) with tamoxifen when the RR = 4.01 (95% CI= 1.70, 10.90). The existence of potentially high- and low-risk groups should be taken into account in any future clinical trials looking at the endometrial safety of selective estrogen receptor modulators (SERMs).

Indication for histological examination of endometrium in breast carcinoma patients receiving tamoxifen therapy.

To investigate the effects of tamoxifen on the uterine endometrium and define the indications for histological examination of endometrium on the thickness of uterine endometrium and on the duration of tamoxifen therapy. The endometrial thickness was measured on the transvaginal ultrasonogram in 40 postmenopausal breast carcinoma patients receiving tamoxifen (tamoxifen group), and control group. Endometrial histological examination was carried out. Receiver operating characteristic (ROC) curve analysis was carried out. Endometrial thickness in the tamoxifen group was 11.2 +/- 5.1 mm, and that of the control group was 3.8 +/- 2.1 mm. The incidence of endometrial abnormalities in the tamoxifen group was greater than that in control group. The cut off values derived from the ROC curve analysis were 9 mm for endometrial thickness, and 24 months for duration of tamoxifen therapy. The histological examination of endometrium should be carried out if the endometrial thickness is more than 9 mm, or the duration of tamoxifen therapy is more than 24 months even if the patients do not have any symptoms.