Tamoxifen Therapy For Breast Cancer Research Articles

Genistein-Chitosan Derivative Nanoparticles for Targeting and Enhancing the Anti-Breast Cancer Effect of Tamoxifen In Vitro

Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies.

Predictive modeling of adverse drug reactions to tamoxifen therapy for breast cancer on base of pharmacogenomic testing.

The present study investigated the analysis of adverse drug reactions (ADRs) to tamoxifen (TAM) in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding enzymes of CYP system and transporters of P-glycoprotein (Pg) and predictive models based on it. A total of 120 women with breast cancer taking adjuvant TAM were examined for the gene polymorphisms such as CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3 and ABCB1 (C3435T). Allelic variants were determined using the real-time polymerase chain reaction method. The research material was double sampling of buccal epithelium. Medical history data and extracts from case histories were used as sources of medical information, on the basis of which questionnaires specially created by us were filled out. An associative analysis showed association with the development of ADRs to TAM indicating their clinical significance from different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9 and ABCB1. The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of ADRs such as hot flashes, dyspepsia, bone pain, and asthenia. Models that include both genetic and non-genetic determinants of ADRs of TAM may further improve the prediction of individual response to TAM.

Predictive modeling of adverse events of tamoxifen therapy for breast cancer (results of a cohort study)

Relevance. Endocrine therapy is the standard treatment for women with ER-positive breast cancer. The clinical response to Tamoxifen is variable. Approximately 30 % of patients with breast cancer will have a recurrence of the disease within 15 years after treatment, despite ongoing endocrine therapy. This article presents the results of a prospective pharmacogenetic cohort study. The study was conducted in 2018–2019. Aim. To analyze adverse drug reactions to Tamoxifen in the adjuvant regimen in breast cancer patients in relation to the carriage of genetic polymorphisms of genes encoding cytochrome P450 enzymes and drug transporter proteins and to build predictive models based on them. A comparative analysis of the relationship between genetic and non-genetic determinants with adverse events on tamoxifen therapy allowed us to build predictive models of their development. Materials and Methods. The study involved 120 women with pre- and postmenopausal breast cancer who underwent genetic testing for CYP and Pg enzyme gene polymorphisms. Entry criteria: a histologically confirmed diagnosis of breast cancer, taking Tamoxifen at the recommended doses, establishing a diagnosis not earlier than 2007, and obtaining informed voluntary consent to participate in the study. Allelic variants were determined using real-time polymerase chain reaction in the Research Institute for Molecular and Personalized Medicine of the Russian Medical Academy of Continuous Professional Education of the Ministry of Healthcare of the Russian Federation. Results. An associative analysis showed their association with the development of adverse drug reactions (ADR) to Tamoxifen, indicating the clinical significance of different genetic polymorphisms of CYP2D6, CYP3A5, CYP2C9 and ABCB1. The complex associative analysis performed using mathematical modeling made it possible to build predictive risk models for the development of such ADR, such as hot flashes, dyspepsia, bone pain, and asthenia. The resulting regression models were statistically significant (p < 0,001) and demonstrated high diagnostic efficiency. This allows them to be implemented in clinical practice. Conclusion. Thus, models that include both genetic and non-genetic determinants of response may further improve the prediction of individual response to tamoxifen

Preliminary results using a kit to measure tamoxifen and metabolites concentrations in capillary blood samples from women with breast cancer

The aim of the study was to compare 3 blood sampling methods, including capillary blood sampling, for determining Tamoxifen (TAM), Z-endoxifen (END), and 4-hydroxytamoxifen (4HT) concentrations. High performance liquid chromatography-mass spectrometry was used to quantify concentrations of TAM, END, and 4HT in plasma, venous blood, and capillary blood samples of 16 participants on TAM therapy for breast cancer. The rhelise kit was used for capillary sampling. Calibration curves using 13C-labeled analogs of TAM, END, and 4HT as internal standards were used for quantifications. A capillary sampling kit was used successfully for all participants. Mean TAM concentrations did not differ significantly in the 3 types of samples. Mean END and 4HT concentrations did differ significantly between capillary and venous blood samples, possibly related to photodegradation in the internal standards prior to use or degradation products with chromatographic retention times similar to the metabolites. TAM, END, and 4HT concentrations were relatively stable when stored for 14 days at 8 °C and 20 °C. Therapeutic drug monitoring of TAM using an innovative kit and capillary blood sampling is feasible. Preliminary data from this study will aid in developing a multicenter, randomized clinical trial of personalized TAM dose monitoring and adjustments, with the goal of enhancing the quality-of-life and outcomes of patients with breast cancer.Clinical Trial Identification: EudraCT No 2017-000641-44.

When Manual Analysis of 12-Lead ECG Holter Plays a Critical Role in Discovering Unknown Patterns of Increased Arrhythmogenic Risk: A Case Report of a Patient Treated with Tamoxifen and Subsequent Pneumonia in COVID-19

Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another “safer” therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.

Abstract A46: KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway in breast cancer

Abstract Krüppel-like factor 4 (KLF4) has critical roles in breast cancer development and progression and several solid tumors. Tamoxifen (TAM) resistance represents a daunting challenge to the successful treatment of breast cancer. KLF4 expression, function, and regulation in the efficacy of TAM therapy in breast cancer have yet to be demonstrated. Here, we investigated the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 was correlated with increased TAM sensitivity in breast cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERa and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy. Knockdown of KLF4 in MCF-7 and BCAP37 cells led to increased TAM resistance, while ectopic KLF4 expression promoted the responsiveness of MCF-7/TAM and T47D cells to TAM. Secondly, ectopic KLF4 overexpression suppressed MCF-7/TAM cell growth, invasion, and migration ability. Besides, KLF4 expression was downregulated in breast cancer tumor tissues and high expression of KLF4 linked to favorable outcome. Mechanistically, KLF4 may enhance the responsiveness of breast cancer cells to TAM through suppressing mitogen-activated protein kinase (MAPK) signaling pathway. We found that ERK and P38 were relatively activated in MCF-7/TAM compared with MCF-7, and treatment with MAPK-specific inhibitors can significantly suppress cell viability. Knockdown of KLF4 activated ERK and P38 and drove MCF-7 cells to become resistant to TAM. Conversely, overexpression of KLF4 in MCF-7/TAM cells suppressed ERK and P38 signaling and resulted in enhanced sensitivity to TAM. Therefore, our findings suggest that KLF4 contributes to TAM efficiency in breast cancer via phosphorylation modification of ERK and P38 signaling. Collectively, this study highlighted the significance of KLF4/MAPK signal interaction in regulating TAM resistance of breast cancer, and suggested that targeting the KLF4/MAPK signaling may be a potential therapeutic strategy for breast cancer treatment, especially for TAM-resistant patients. Note: This abstract was not presented at the conference. Citation Format: Yunlu Jia, Wang Linbo. KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway in breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr A46.

Association of microRNA-7 and its binding partner CDR1-AS with the prognosis and prediction of 1st-line tamoxifen therapy in breast cancer

The large number of non-coding RNAs (ncRNAs) and their breadth of functionalities has fuelled many studies on their roles in cancer. We previously linked four microRNAs to breast cancer prognosis. One of these microRNAs, hsa-miR-7, was found to be regulated by another type of ncRNA, the circular non-coding RNA (circRNA) CDR1-AS, which contains multiple hsa-miR-7 binding sites. Based on this finding, we studied the potential clinical value of this circRNA on breast cancer prognosis in a cohort based on a cohort that was previously analysed for hsa-miR-7 and in an adjuvant hormone-naïve cohort for 1st-line tamoxifen treatment outcomes, in which we also analysed hsa-miR-7. A negative correlation was observed between hsa-miR-7 and CDR1-AS in both cohorts. Despite associations with various clinical metrics (e.g., tumour grade, tumour size, and relapse location), CDR1-AS was neither prognostic nor predictive of relevant outcomes in our cohorts. However, we did observe stromal CDR1-AS expression, suggesting a possible cell-type specific interaction. Next to the known association of hsa-miR-7 expression with poor prognosis in primary breast cancer, we found that high hsa-miR-7 expression was predictive of an adverse response to tamoxifen therapy and poor progression-free and post-relapse overall survival in patients with recurrent disease.

Making use of modeling and simulations: Towards individualized tamoxifen therapy inbreast cancer .

Making use of modeling and simulations: Towards individualized tamoxifen therapy inbreast cancer .

Mullerian adenosarcoma of the uterus associated with tamoxifen treatment for breast cancer

Mullerian adenosarcoma following tamoxifen therapy is a rare condition. Our aim was to report the youngest patient in the literature with uterine mullerian adenosarcoma who was undergoing tamoxifen therapy for breast cancer. A premenopausal woman aged 38 years who was undergoing tamoxifen therapy for breast cancer, was admitted with symptoms of lower abdominal pain and irregular vaginal bleeding and malodorous vaginal discharge that had continued for at least 6 months. A pelvic examination revealed a large and malodorous polypoid mass protruding through the cervix and an enlarged uterus. A biopsy from the protruding polypoid mass was reported as a large area of necrosis with neoplastic mesenchymal cells. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, pelvic-paraaortic lymph node dissection, and omentectomie. The histologic diagnosis was Mullerian adenosarcoma. As a result, she was discharged to the oncology department. The woman is alive and her chemoradiotherapy treatment is ongoing.The role of tamoxifen therapy in the development of endometrial neoplasms remains unclear, but all cases of endometrial thickening and vaginal bleeding must be investigated for Mullerian adenosarcoma in tamoxifen users.

Hysteroscopic Resection of Large Endometrial Polyp Secondary to Tamoxifen Therapy for Breast Cancer

Hysteroscopic Resection of Large Endometrial Polyp Secondary to Tamoxifen Therapy for Breast Cancer

Risk of Gastric and Colorectal Cancer After Tamoxifen Use for Breast Cancer: A Systematic Review and Meta-Analysis.

It is still controversial whether tamoxifen use for breast cancer will simultaneously cause gastric and colorectal cancer. In this study, we aimed to evaluate the association between tamoxifen use and the risk of gastric and colorectal cancer by performing a systematic review and meta-analysis. A comprehensive literature search for relevant studies published from 1969 to October 2013 was performed in PubMed, MEDLINE, and ISI Web of Science. Only articles in which gastric and colorectal cancer was reported after tamoxifen therapy for breast cancer were included. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using both the random-effects and fixed-effects models. We found a total of 9 studies that met the inclusion criteria for the analysis of tamoxifen use and incidence of gastric and colorectal cancer. Among these studies, 7 were involved with both gastric and colorectal cancer, 1 with gastric cancer and 1 with colorectal cancer. The random-effects model results showed that tamoxifen use for breast cancer was not a risk factor for either gastric cancer (RR=0.92; 95% CI, 0.41-2.07, P=0.84) or colorectal cancer (RR=1.05; 95% CI, 0.90-1.21, P=0.54). Sensitivity analysis indicated that the duration or dose of tamoxifen use had no effect on these 2 gastrointestinal tumors (P>0.05). Stratified analysis showed that tamoxifen use was not associated with the increased risk of gastric and colorectal cancer regardless of whether the latency interval after breast cancer diagnosis was <5 or ≥5 years. Our meta-analysis results indicate that there was no substantial increase in gastric and colorectal cancer among the tamoxifen-treated female patients.

Pharmacogenomics toward personalized tamoxifen therapy for breast cancer.

Tamoxifen has been used not only for the treatment or prevention of recurrence in patients with estrogen receptor positive breast cancers but also for recurrent breast cancer. Because CYP2D6 is known to be an important enzyme responsible for the generation of the potent tamoxifen metabolite, 'endoxifen', lots of studies reported that genetic variation which reduced its enzyme activity were associated with poor clinical outcome of breast cancer patients treated with tamoxifen. However, there are some discrepant reports questioning the association between CYP2D6 genotype and clinical outcome after tamoxifen therapy. Dose-adjustment study of tamoxifen based on CYP2D6 genotypes provides the evidence that dose adjustment is useful for the patients carrying reduced or null allele of CYP2D6 to maintain the effective endoxifen level. This review describes critical issues in pharmacogenomic studies as well as summarizes the results of the association of CYP2D6 genotype with tamoxifen efficacy.

Uterine carcinosarcoma/malignant mixed Müllerian tumor incidence is increased in women with breast cancer, but independent of hormone therapy.

Uterine carcinosarcoma/malignant mixed Mullerian tumor (UC/MMMT) is an uncommon and aggressive gynecological malignancy with poor prognosis. Tumors arise from monoclonal carcinoma cells derived from embryonal mesoderm, which exhibit sarcomatous metaplasia. UC/MMMT usually occurs in postmenopausal women and accounts for 2%-5% of all uterine malignancies [1,2]. The five-year survival rates are particularly poor (21%-39%). Several case reports and case series describe UC/MMMT occurring after tamoxifen therapy for breast cancer [3,4,5,6,7,8,9]. Retrospective studies suggest that the increased incidence of these high-risk malignancies is greater than the observed increase in incidence of endometrial tumors generally following tamoxifen therapy [10,11,12,13], though the number of subjects with UC/MMMT in any of these studies is small. The increase in uterine cancers generally following tamoxifen therapy is thought to be driven by the estrogen receptor alpha (ERα) through a positive trophic effect on the uterine corpus. Although tamoxifen binds ERβ with equal affinity, there is no observed activation of this receptor [14,15]. Whether ER activation exerts any positive effect on UC/MMMTs remains equivocal. Other studies suggest that tamoxifen may upregulate expression of the HER2/neu oncogene in UC/MMMT cells [16,17], although any potential effect on the behavior of these malignancies is far from clear. As tamoxifen metabolites can covalently bind DNA, principally forming (E)- and (Z)-α-(deoxyguanosin-N2-yl)-4-hydroxytamoxifen adducts [18], the possibility that tamoxifen therapy is inherently carcinogenic has also been considered. However, tamoxifen-DNA adduct formation in uterine tissues following oral administration occurs at levels too low to be consistent with this being the mechanism driving such endometrial cancers [19]. We identified two unrelated women who developed UC/MMMT as a second primary malignancy following BRCA1-associated breast cancer. Neither of these women received hormone therapy, as their tumors were histologically determined to be unresponsive to hormone therapy (i.e., ER-/progesterone receptor [PR]-). Patient 1 had BRCA1 c.5503C>T (p.Arg1835*), developed breast cancer at 36 years, which was managed with lumpectomy and local radiotherapy, and subsequently developed UC/MMMT at 48 years. Patient 2 had BRCA1 c.2560_2561dupGC (p.Gln855fs), developed breast cancer at 34 years, again treated with lumpectomy and local radiotherapy, and was found to have UC/MMMT at 56 years. Although BRCA1 mutation carriers are at increased risk of developing endometrial cancers compared to the general population, most of this risk is attributable to tamoxifen use [20]. It has also been suggested that BRCA1 mutations may predispose carriers to uterine papillary serous carcinoma specifically [21,22]. However, UC/MMMT is not recognized as part of the BRCA1 phenotype. Prompted by this unexpected finding, we conducted a retrospective population-based study to establish whether an association exists between breast cancer and UC/MMMT generally and whether a breast tumor being ER-/PR- has any bearing on this.

Carcinosarcoma of the uterus: Possible sequelae of long-term tamoxifen therapy for breast cancer

Carcinosarcoma (CS) of the uterus is rare and accounts for 1–2% of all uterine malignancies, occur commonly in postmenopausal women. These are highly aggressive tumors with poor prognosis and often present at advanced stage. Tamoxifen (TAM) has been known to increase the incidence of endometrial carcinoma from 1 to 2 cases per 1000 women/year and of uterine sarcoma from 0.04 to 0.17 cases per 1000 women/year. TAM has weakly estrogenic properties that can produce endometrial cell proliferation and, consequently, TAM use increases the risk of endometrial cancer by approximately two- to three-fold. Currently, no consensus is present regarding the management of Uterine CS. However, surgery plays an important role in the management along with chemotherapy (CT) and radiotherapy as an adjuvant. We report a case of a woman who developed malignant mixed mullerian tumor of uterus after taking TAM for 6 years as adjuvant hormonal therapy for breast carcinoma.

Hysteroscopic Resection of Endometrial Polyp Secondary to Tamoxifen Therapy for Breast Cancer

Hysteroscopic Resection of Endometrial Polyp Secondary to Tamoxifen Therapy for Breast Cancer

Circadian and Melatonin Disruption by Exposure to Light at Night Drives Intrinsic Resistance to Tamoxifen Therapy in Breast Cancer

Resistance to endocrine therapy is a major impediment to successful treatment of breast cancer. Preclinical and clinical evidence links resistance to antiestrogen drugs in breast cancer cells with the overexpression and/or activation of various pro-oncogenic tyrosine kinases. Disruption of circadian rhythms by night shift work or disturbed sleep-wake cycles may lead to an increased risk of breast cancer and other diseases. Moreover, light exposure at night (LEN) suppresses the nocturnal production of melatonin that inhibits breast cancer growth. In this study, we used a rat model of estrogen receptor (ERα(+)) MCF-7 tumor xenografts to demonstrate how altering light/dark cycles with dim LEN (dLEN) speed the development of breast tumors, increasing their metabolism and growth and conferring an intrinsic resistance to tamoxifen therapy. These characteristics were not observed in animals in which the circadian melatonin rhythm was not disrupted, or in animals subjected to dLEN if they received nocturnal melatonin replacement. Strikingly, our results also showed that melatonin acted both as a tumor metabolic inhibitor and a circadian-regulated kinase inhibitor to reestablish the sensitivity of breast tumors to tamoxifen and tumor regression. Together, our findings show how dLEN-mediated disturbances in nocturnal melatonin production can render tumors insensitive to tamoxifen.

Patients' Understanding of How Genotype Variation Affects Benefits of Tamoxifen Therapy for Breast Cancer

Background: CYP2D6 is a critical enzyme in the metabolism of tamoxifen and potentially a key determinant in breast cancer outcomes. Our study examined patients' beliefs about how the CYP2D6 genotype would affect their prognoses. Methods: Women enrolled in a pharmacogenomic clinical trial and on tamoxifen for prevention or treatment of breast cancer underwent CYP2D6 genotyping (EM = extensive, IM = intermediate, PM = poor metabolizing alleles). The informed consent said that the purpose of the trial was to examine effects of dose adjustment based on genotype, but that clinical benefits were uncertain. Our embedded sub-study surveyed 320 patients prior to receiving their genotypes. We experimentally manipulated 6 vignettes to describe hypothetical tamoxifen treatment (no or yes) and hypothetical genotype (EM, IM or PM). For each vignette, women gave their perceived recurrence risk (RR; 0-100%). Results: Women believed that genotype would not affect their RR if they did not take tamoxifen (p = 0.06). However, women believed that if prescribed tamoxifen, genotype would affect their RR (22% if EM, 30% if IM and 40% if PM, p < 0.001). Conclusion: Women believed that extensive tamoxifen metabolizers had better prognoses, despite study materials stating uncertainty about any benefit. The rapidly changing nature of genomic science calls for caution when communicating clinical utility.

Patients' Understanding of How Genotype Variation Affects Benefits of Tamoxifen Therapy for Breast Cancer

Patients' Understanding of How Genotype Variation Affects Benefits of Tamoxifen Therapy for Breast Cancer

Tamoxifen Therapy in Breast Cancer: Do Apolipoprotein E Genotype and Menopausal State Affect Plasma Lipid Changes Induced by the Drug?

This study examines the lipid profile change produced in response to tamoxifen (TAM) treatment, and its possible relationship with both apolipoprotein E genotype and menopausal state in patients with breast cancer. Blood samples were collected from 86 Spanish women with breast cancer before initiating TAM treatment and in the following 6, 12 and 18 months of treatment. Plasma lipid levels (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were determined using an automatic analyzer. Genotypes for apolipoprotein E (ApoE) were identified by PCR-RFLP using the HhaI enzyme. In all patients, significant reductions in total cholesterol and LDL-cholesterol concentrations and a significant increase in triglyceride concentrations were observed after 6, 12, and 18 months of TAM treatment compared to baseline (p<0.01 for each time point). In the subset of APOE4-negative patients, triglyceride concentrations also significantly increased after 6, 12, and 18 months of treatment (p=0.019, p=0.045, p=0.001, respectively), while APOE4-positive patients showed no significant lipid changes at 12 and 18 months. However, after 18 months of TAM treatment the overall triglyceride concentrations had risen by 24.75% in APOE4-negative patients vs 29.9% in APOE4-positive patients. In postmenopausal women, significant reductions in total cholesterol, LDL-cholesterol and LDL/HDL ratios were observed at each time point (p<0.020 for each). TAM treatment induced similar plasma triglyceride increases in patients with positive or negative APOE genotype. Compared to premenopausal patients, postmenopausal breast cancer patients showed a more beneficial lipid profile change in response to treatment.

Sonohysterography for evaluation of endometrial abnormalities associated with tamoxifen therapy for breast cancer

ObjectiveTo evaluate sonohysterography for the diagnosis of endometrial abnormalities in women treated with tamoxifen for breast cancer. Patients and methodsWe assessed 37 women treated with tamoxifen for breast cancer who underwent sonohysterography and correlative endometrial biopsy for evaluation of postmenopausal bleeding or thickened endometrium greater than 8mm. In 14 patients, endometrial biopsy was followed by endovaginal sonography to ensure removal of endometrial pathology. Sonohysterography findings were compared with histopathology results. ResultsSonohysterography findings coincided with histopathology results in 27 of 37 cases including 19 of 23 cases of endometrial polyps, 6 of 8 cases with thickened endometria and two cases had normal endometrium. Sonohysterography findings did not coincide with histopathology in 3 of the 14 cases who underwent endovaginal sonography after endometrial biopsy compared to 7 of the 23 cases who did not undergo such examination and 4 of these missed 7 cases were for endometrial polyps. ConclusionSonohysterography is a useful procedure for the diagnosis of endometrial abnormalities in tamoxifen-treated women. Endometrial abnormalities are better diagnosed on sonohysterography than on endometrial biopsy which has the limitation of some missed endometrial polyps, a problem that may be minimized by performing endovaginal sonography after endometrial biopsy.