Thymoquinone Increased Expression of CD4CD25Treg in Sprague-Dawley Rats Induced Dimethylbenzanthracene

BACKGROUND: The carcinogen dimethylbenzanthracene (DMBA) is immunotoxic. Thymoquinone, meanwhile, is known to have antioxidant and anti-inflammatory effects. AIM: This study aims to determine the effect of thymoquinone and tamoxifen on the CD4CD25Treg count in Sprague-Dawley (SD) rats induced by DMBA. METHODS: The 50 SD rats were divided into five groups. Group I (normal control) was given standard drinking and food. Group II was given thymoquinone, Group III was given tamoxifen, Group IV was given DMBA, and Group V was given solvent control. Thymoquinone, tamoxifen, and solvent control administration started 2 weeks before DMBA administration and continued during DMBA induction. In the 3rd week, except for the normal group, all groups were created to be induced with 10 × 20 mg/kg body weight of DMBA for 5 weeks. In the 21st week, surgery and data collection were performed. The hematology profile and CD4CD25Treg number were carried out employing a flow cytometer. The difference in the average number of CD4CD25Treg and blood cells between groups was analyzed with one-way analysis of variance RESULTS: The results revealed that DMBA induction reduced the number of erythrocytes, HB levels, platelet counts, and leukocyte counts (p < 0.05). The administration of thymoquinone and tamoxifen reduced the hematopoiesis effect of DMBA. The thymoquinone and tamoxifen group had a higher number of CD4CD25Treg and leukocytes than the DMBA group (p < 0.05). CONCLUSION: There was no difference in the average CD4CD25Treg, leukocyte count, lymphocyte count, and monocyte count between the thymoquinone and the tamoxifen groups (p > 0.05).

Tamoxifen for treatment of abnormal uterine bleeding in etonorgstrel implant users: a randomized clinical trial

Background: The current study aims to compare the use of tamoxifen and oral contraceptive pills in women using implanon and complain with irregular uterine bleeding.Methods: Women attended family planning clinic using implanon presented by bleeding were invited to participate in the study. They were randomized into two groups: Group A: 100 women received Tamoxifen 10 mg twice daily for 10 days taken at the onset of an episode of bleeding or spotting episode. Group B: 100 women received Combined oral contraceptive pills (microcept) once daily for 21 days take at the onset of an episode of bleeding or spotting episode.Results: No difference regarding the baseline criteria of both groups. No difference between both groups regarding the duration of irregular bleeding in the implanon users (p=0.090). Additionally, the number of bleeding days and spotting in the last month was similar in both groups (p=0.554). The percentage of women who stopped bleeding during the period of treatment is 84% in the tamoxifen group and 92% in the COCs group, but the COCs needs longer treatment time, where the mean of days required to stop bleeding is 5.03±1.8 days in the tamoxifen group and 6.5±2.5 in the COCs group. Headache and nausea were the most prominent adverse effects found in the COCs group (p=0.000).Conclusions: Oral administration of tamoxifen 10 mg twice daily for 10 days is effective on stopping bleeding attacks in implanon users.

Choroidal thickness, ganglion cell complex and photoreceptor outer segment length evaluation in patients receiving tamoxifen therapy by spectral domain optical coherence tomography

Background To evaluate choroidal thickness, ganglion cell complex and photoreceptor outer segment length in patients with breast cancer undergoing tamoxifen therapy using spectral domain optical coherence tomography (SD-OCT) and to compare the results to normal eyes. Methods Fourty four patients with breast cancer undergoing tamoxifen therapy and fourty one 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 μm, 1000 μm, 1500 μm) and temporal (temporal distance to fovea 500 μm, 1000 μm, 1500 μm) choroidal thickness measurements were performed using 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 thicknesses of the ganglion cell complex (GCC) by adding the macular retinal nerve fiber layer, macular ganglion cell layer, and macular internal plexiform layer parameters. The photoreceptor outer segment (PROS) length was determined by manually as the distance from inner surface of ellipsoid zone to inner surface of retina pigment epithelium after automatic retinal segmentation. Results The mean choroidal thickness measurements were statistically greater in 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 5 patients (11.3%) in tamoxifen group. 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 thicknesses in all inner rings of ETDRS inlay and only in nasal outer ring (p:0.027, p:0.002, p:0.002, p:0.001 and p:0.030; respectively). No statistically significant difference was found between the groups in terms of mean subfoveal PROS length. Conclusions SD-OCT provides valuable information in identifying the structural changes and evaluation of ocular findings in patients receiving tamoxifen therapy. Increasing choroidal thickness, PPE, thinning GCC were detected in tamoxifen users. These OCT findings may be an early indicator of retinal toxicity for patients undergoing tamoxifen therapy in follow-up period.

A comparative study of Centchroman, Tamoxifen and Danazol in management of cyclical mastalgia

Background: Mastalgia is a common problem and 60-70% women encounter it at least once in their lifetime. Many drugs have been used and are been used with varying response, like Tamoxifen, Danazol, primrose oil, topical analgesics and recently Centchroman. The objective of the present study was to compare the three most commonly used drugs in the treatment of mastalgia, namely Centchroman, Tamoxifen and Danazol with a placebo.Methods: All consecutive female patients more than 25 years of age with history of mastalgia for more than 3 months were taken up for the study. Patients were distributed into four groups and administered Centchroman, danazol, tamoxifen and placebo, respectively.Results: In present study of 78 patients, the median visual analogue score (VAS) in Centchroman group were 3, 1 and 3 after treatment of 4, 12 and 24 weeks, respectively with a pre-treatment VAS of 8. Similarly, in the danazol group, VAS at 4, 12 and 24 weeks were 4, 1.5 and 5, respectively. In the Tamoxifen group it was 4, 1 and 3 after treatment for 4, 12 and 24 weeks. On comparison, Centchroman and Tamoxifen both had better pain relief than danazol at 24 weeks (p <0.001) while Centchroman and Tamoxifen had comparable results (p >0.05) despite Centchroman having a lower mean VAS score.Conclusions: Mild cyclical mastalgia can be treated with reassurance and lifestyle measures. Moderate to severe mastalgia usually require drug treatment. Centchroman, Danazol and Tamoxifen are effective. Centchroman appears to have better pain relief relative to the rest.

Qianlongtong Inhibits Proliferation and Induces Apoptosis of Hyperplastic Prostate Cells

Qianlongtong is a compound made from traditional Chinese herbs and it has proven to be very effective to treat patients with benign prostate hypertrophy. However, its mechanism is still unknown. This study is designed to investigate the effect of Qianlongtong on proliferation and apoptosis of hyperplastic prostate cells. Flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were used to assess proliferation and apoptosis of hyperplastic prostate cells in the following groups: control group, tamoxifen group, and groups with low, moderate, and high dosage of Qianlongtong. Reverse transcription-polymerase chain reaction analysis was used to investigate the underlying mechanisms for increased apoptosis. Cells treated with Qianlongtong were mainly blocked in the G0/G1 phase. The apoptotic index of each group was significantly higher than that in the control group. The apoptotic index in the high- and moderate-dosage groups was similar to that in the tamoxifen group. The high- and moderate-dosage groups had lower Bcl-2 and higher Bax messenger RNA (mRNA) levels compared with the control group. Qianlongtong inhibits proliferation and promotes the apoptosis of hyperplastic prostate cells.

Aromatase inhibitors are associated with a higher fracture risk than tamoxifen: a systematic review and meta-analysis

Background: In this paper, our aim was to systematically evaluate published evidence of bone fracture risk associated with tamoxifen and aromatase inhibitors in women aged 65 and under, and diagnosed with nonmetastatic breast cancer. Methods: We comprehensively searched MEDLINE, EMBASE and CINAHL databases from January 1997 through May 2015, and reference lists of the selected articles to identify English-language randomized controlled trials and cohort studies of fracture risk. Two independent reviewers screened articles and assessed methodological quality using Risk of Bias assessment for randomized controlled trials and the Newcastle–Ottawa Scale for cohort studies. Fracture risk was estimated as pooled risk ratios using a random-effects model and inverse variance method. Results: Of 1926 identified articles, 21 independent studies fulfilled our selection criteria. Similar fracture risk was observed in women treated and not treated with tamoxifen [pooled risk ratio (RR) 0.95; 95% confidence interval (CI) 0.84–1.07]. A 35% (95% CI 1.21–1.51) higher fracture risk was observed in the aromatase inhibitor group compared with the tamoxifen group. A 17% (95% CI 1.07–1.28) higher fracture risk was observed in the aromatase inhibitor group than the no aromatase inhibitor group. Compared with the tamoxifen group, aromatase inhibitor-associated fracture risk increased by 33% (pooled RR 1.33; 95% CI 1.21–1.47) during the tamoxifen/aromatase inhibitor treatment period, but did not increase (pooled RR 0.99; 95% CI 0.72–1.37) during the post-tamoxifen/aromatase inhibitor treatment period. Conclusions: Fracture risk is significantly higher in women treated with aromatase inhibitors, especially during the treatment period. Tamoxifen is not associated with lower fracture risk while tamoxifen could potentially preserve bone mass. Better osteoporosis management programs, especially during the treatment period, are needed for this group of women.

Post-menopausal bleeding – Is transvaginal ultrasound a useful first-line investigation in tamoxifen users?

Objective To evaluate the role of transvaginal ultrasound triage in women with a history of tamoxifen treatment who present with post-menopausal bleeding. Study design A retrospective review was undertaken of patients who presented with symptoms of post-menopausal bleeding and underwent ultrasound triage. Endometrial thickness and ultrasonographic features were then correlated with hysteroscopic and histopathological outcome data. The findings and outcomes for women with a history of tamoxifen use (tamoxifen group) were compared to those who had not taken tamoxifen (non-tamoxifen group). Results A total of 614 women with post-menopausal bleeding underwent transvaginal ultrasound triage, of whom 53 had a history of current or previous tamoxifen treatment. An endometrial thickness of ≥5 mm or the presence of other abnormal features was used to triage women to further investigation by hysteroscopy and biopsy. Endometrial thickness was significantly greater in the tamoxifen group (11 mm vs. 6 mm). Nearly all of the tamoxifen group were triaged to further investigation (98.1%), compared with significantly fewer in the non-tamoxifen group (68.3%) Overall, the incidence of endometrial pathology was also significantly higher in tamoxifen patients (43.4% vs. 31.7%). Conclusion For women presenting with post-menopausal bleeding, the use of transvaginal ultrasound as a triage tool is rarely helpful in evaluating women who have a history as tamoxifen use, as most will require further investigation with hysteroscopy and biopsy. A post-menopausal bleeding protocol that omits transvaginal ultrasound for women with a history of tamoxifen use may be an appropriate and effective pathway for managing these patients.

Centchroman versus Tamoxifen in the management of mastalgia: a randomized controlled clinical trial

Introduction and Objective: Mastalgia is defined as painful nodularity for more than 1 week of menstrual cycle. The long list of drugs highlights the ongoing debate about the drug of choice for the management of mastalgia. So in this study, we compared the effectiveness and cost of Centchroman and Tamoxifen in the management of mastalgia.Materials and methods: A total of 106 female patients with the clinical diagnosis of mastalgia were enrolled in the study and randomized to 1:1 ratio into Centchroman and Tamoxifen group for a period of 1 year. The duration of therapy was 3 months. All patients completed the study and follow up. The response of therapy was assessed on 1, 2, 3 and 6 months by using a Visual Analogue Scale (VAS).Results: Baseline mean VAS score was 6.25 in Tamoxifen and 6.49 in Centchroman group.There was marked improvement in VAS score after the treatment in both the groups, which was statistically significant with greater reduction in Centchroman group(p= 0.001).The number of patients who achieved VAS less than 3 were 51(96.2%) in Centchroman and 49(92.5%) in Tamoxifen group at the end of treatment. Tamoxifen was found to be statistically significant and cost-effective (p <0.001) in comparison to Centchroman.Conclusion: We conclude that Centchroman is not inferior to Tamoxifen and both the drugs effectively reduced pain, however Centchroman reduced the pain more than Tamoxifen.

Switching to Anastrozole Versus Continued Tamoxifen Treatment of Early Breast Cancer: Preliminary Results of the Italian Tamoxifen Anastrozole Trial

Purpose Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor–positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required. Patients and Methods We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points. Results Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor–positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04). Conclusion Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.

Biomarker Changes During Neoadjuvant Anastrozole, Tamoxifen, or the Combination: Influence of Hormonal Status and HER-2 in Breast Cancer—A Study from the IMPACT Trialists

Purpose To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. Patients and Methods The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. Results A decrease in the proliferation marker Ki67 occurred in the majority of patients: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. Conclusion These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.