Tamoxifen Group Research Articles

Evaluation of trichodynia (hair pain) during chemotherapy or tamoxifen treatment in breast cancer patients.

In women receiving antineoplastic therapy, hair loss is often accompanied by distressing hair or scalp sensations, such as hair pain (trichodynia) and pruritus. A scientific approach to objectively evaluate the course and characteristics of these unpleasant sensations is of great importance for the establishment of treatment strategies. An observational cohort study was conducted in 34 female breast cancer patients, postoperatively undergoing chemotherapy (group C, n = 17) or endocrine therapy with tamoxifen (group T, n = 17). For 28 weeks after therapy initiation, patients experiencing hair pain and/or scalp pruritus were required to complete a specially developed diary, based on a modification of pain questionnaires. Sensations were journalized in terms of time of onset, duration, intensity on a numeric rating scale, dependence on touching the scalp or hair and character of the sensation, chosen from given descriptors or using own words. In group C, all patients who completed the questionnaire experienced hair and scalp sensations: 87% both trichodynia and pruritus, 13% trichodynia only. Reported intensities ranged between 1 and 10. In group T, 31% of participants reported hair and scalp sensations: 12% both trichodynia and pruritus, 12% pruritus only, 7% trichodynia only. Intensities were rated between 1 and 5. No sensations were reported after week 11 in either group. Hair and scalp sensations in group C were significantly more common, lasted longer, and were of greater intensity and more differentiated qualities than in group T. The occurrence of trichodynia in chemotherapy patients corresponded with the onset and duration of hair loss, thus suggesting a possible correlation.

Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: Possible underlying pathway of miR-21

Exercise training has an anti-tumor effect and can reduce tumor growth; however, the exact underlying mechanisms of its protective effects are still obscure. MicroRNA (miR)-21 is a predictor in cancer survival, and has a potential use as an indicator of therapeutic outcome in breast malignancies. Forty-eight female BALB/c mice were equally divided into six groups to investigate the effects of interval exercise training with tamoxifen on miR-21 expression and its possible assumed mechanisms in an estrogen receptor-positive breast cancer model. ELISA, immunohistochemistry, western blot, qRT-PCR assays were performed at the end of the study. Tumor size was significantly declined in exercise training and tamoxifen groups compared to tumor group (P<0.05). Expression of miR-21 was significantly down-regulated in trained and tamoxifen treated mice in comparison with tumor group (P<0.05). Exercise training was as effective as tamoxifen treatment in decreasing serum estradiol and ER-α expression (P<0.05). Exercise training and tamoxifen reduced tumor IL-6 levels, NF-kB and STAT3 expressions, and up-regulated TPM1 and PDCD4 expressions (P<0.05). Both exercise and tamoxifen had synergistic effects in reducing miR-21 and Bcl-2, and up-regulating PDCD4 expression. Results showed that interval exercise training may reduce mammary tumor burden in mice through possible underlying pathway of miR-21.

Tamoxifen is a potent antioxidant modulator for sperm quality in patients with idiopathic oligoasthenospermia.

To explore the new mechanisms of tamoxifen (TAM) in the treatment for patients with idiopathic oligoasthenospermia-antioxidation. In a prospective, randomized, controlled clinical trial, 120 cases of idiopathic oligoasthenospermia were enrolled and randomly assigned to the indomethacin group (n = 60) treated with indomethacin (25 mg, bid) and TAM group (n = 60) treated with TAM (10 mg, bid) for 3 months. Before and after treatment, we evaluated semen parameters, serum malondialdehyde (MDA) and total antioxidant capacity (TAC), seminal plasma MDA and TAC, spermatozoa intracellular reactive oxygen species (ROS), sperm succinate dehydrogenase (SDH) activity, sperm mitochondrial membrane potential (MMP), and sperm adenosine triphosphate (ATP) content. The independent t test and one-way repeated measures analysis of variance were used to compare the variables between and within two groups. In the indomethacin group, the percentage of progressive motile sperms, total motility, sperm MMP, and ATP content were increased significantly after 3-month treatment (P < 0.05). In the TAM group, total sperm count, sperm concentration, the percentage of progressive motile sperms, total motility, serum and seminal plasma TAC, sperm MMP, and ATP content were significantly improved or increased (P < 0.05), while spermatozoa intracellular ROS was significantly decreased (P < 0.05). Compared to the indomethacin group, TAM treatment showed better improvement in total sperm count, sperm concentration, serum TAC, seminal plasma TAC, spermatozoa intracellular ROS, and sperm SDH activity. TAM treatment can significantly improve sperm quality, which is achieved through alleviating oxidative stress, improving sperm mitochondrial functionality, and subsequently increasing sperm motility.

Association of tamoxifen use and ovarian function in patients with invasive or pre-invasive breast cancer.

The impact of long-term tamoxifen therapy on ovarian function is not known. Understanding these effects will help reproductive-aged patients who desire future pregnancy make more informed decisions regarding their treatment. This is a retrospective cohort study in patients identified through the UCSF Cancer Registry and SPORE database. We enrolled women with a history of ductal carcinoma in situ (DCIS) or early stage invasive breast cancer who were premenopausal at diagnosis and did not receive chemotherapy. Menstrual histories were obtained through electronic and paper surveys. We compared the age of menopause onset and menstrual pattern changes between women who received tamoxifen (TAM) and those who did not receive tamoxifen (control). Neither group received chemotherapy. 250 subjects were included in this study (125 TAM, 125 control). Mean age of menopause onset was 51.0 for both the groups and was not associated with duration of tamoxifen use or the age at tamoxifen initiation. Menstrual pattern changes, including amenorrhea, were more frequent in the TAM group than control group (any change: 48% TAM vs. 15 % control, p < 0.001; amenorrhea: 22% TAM vs. 3% control, p < 0.001). Older age was associated with an increased risk of developing amenorrhea within 6 months of starting tamoxifen (HR 1.32, p < 0.001). Menstrual pattern changes are common in premenopausal women taking tamoxifen. Tamoxifen use in the absence of chemotherapy is not associated with an earlier age onset of menopause in patients with DCIS or invasive breast cancer and is unlikely to significantly accelerate ovarian aging.

Effect of tamoxifen on fatty degeneration and atrophy of rotator cuff muscles in chronic rotator cuff tear: An animal model study.

Fatty degeneration of the rotator cuff muscles is an irreversible change resulting from chronic rotator cuff tear and is associated with poor clinical outcomes following rotator cuff repair. We evaluated the effect of Tamoxifen, a competitive estrogen receptor inhibitor, on fatty degeneration using a mouse model for chronic rotator cuff tear. Sixteen adult mice were divided into two diet groups (Tamoxifen vs. Regular) and subjected to surgical creation of a large rotator cuff tear and suprascapular nerve transection in their left shoulder with the right shoulder serving as a control. The rotator cuff muscles were harvested at 16 weeks and subjected to histology and RT-PCR for adipogenic and myogenic markers. Histology showed substantially decreased atrophy and endomysial inflammation in Tamoxifen group, but no significant differences in the amount of intramuscular adipocytes and lipid droplets compared to the Regular group. With RT-PCR, the operated shoulders showed significant upregulation of myogenin and PPAR-γ, and downregulation of myostatin compared to the nonsurgical shoulder. No significant differences of gene expression were found between the two diet groups. Our study demonstrated that tamoxifen diet leads to decreased muscle atrophy and inflammatory changes following chronic rotator cuff tear, but has no apparent effect on adipogenesis.

Association between tamoxifen treatment and the development of different stages ofnonalcoholic fatty liver disease among breast cancer patients.

For estrogen-receptor positive breast cancer cases, tamoxifen has been the most important adjuvant hormonal therapy for the purpose of reducing recurrence rates and prolonging disease free survival. However, several side effects have been noticed, and fatty liver is one of the most common side effects among them. Since fatty liver is a common problem in the general population, we wanted to examine the effects of tamoxifen under pre-existing fatty liver conditions and evaluate the prevalence of tamoxifen-related impaired liver function. We recruited breast cancer cases at ages 20-70 years and divided them into tamoxifen or control groups. Personal information was collected, and fasting blood tests and abdominal ultrasound were performed. The changes of fatty liver degree between the initial and follow-up ultrasound were divided into five categories. Of the 406 enrolled participants, 266 were in the tamoxifen group and 140 were in the control group. The tamoxifen group had a higher risk of newly developed fatty liver [hazard ratio (HR)=3.69; 95% confidence interval (CI) 1.67-8.13), lower rate of improved fatty liver (HR=0.33; 95% CI 0.15-0.75), and higher rate of worsened fatty liver (HR=2.11; 95% CI 1.02-4.35). The current study suggests that tamoxifen treatment is associated with the risk of fatty liver either by increasing the risk of newly developed fatty liver conditions or worsening previous fatty liver conditions, and even retarding fatty liver improvement.

Abstract P1-12-09: Possibility of GnRH agonist plus tamoxifen as an alternative treatment to AC (adriamycin plus cyclophosphamide) chemotherapy plus tamoxifen treatment in premenopausal hormone responsive HER2 negative breast cancer patients

Abstract Background: The purpose of this study is to compare the treatment outcomes using GnRH agonist plus tamoxifen, and adriamycin and cyclophopsphamide(AC) containing chemotherapy plus tamoxifen in hormone responsive premenopausal node negative breast cancer patients. Methods: Total 1027 premenopausal women with node negative, hormone receptor positive, Her-2 negative breast cancer were included in this retrospective cohort study. 595 patients (57.9%) were treated with GnRH agonist together with tamoxifen, and 432 patients (42.1%) were treated with adriamycin and cyclophsophamide containing chemotherapy with tamoxifen. Results: A median follow up period was81 months. In pT1 disease, 7 year DFS (disease free survival)was 98.9% for GnRH agonist plus tamoxifen group and 97.4% for chemotherapy plus tamoxifen group, and in pT2 disease, 7 year DSS was 99.1% for GnRH agonist plus tamoxifen group, and 96.9% for chemotherapy plus tamoxifen groupwith nostatisticalsignificance (p=0.252 &amp; 0.230).In pT1 disease, 7 year RFS was 95.4% for GnRH agonist plus tamoxifen group and 92.9% for chemotherapy plus tamoxifen group, and in pT2 disease, 7 year RFS was 91.6% for GnRH agonist plus tamoxifen group, and 91.7% for chemotherapy plus tamoxifen group with no statistical difference between two treatment groups (p=0.353 &amp; 0.836). In subgroup analysis, ER+/PR+ patients and patientsyounger than 40 years old showed slightly better survival inGnRHagnonist plus tamoxifen group when compared to chemotherapy plus tamoxifen group with p-value of 0.046 &amp; 0.018. Conclusion: Adding GnRH agonist to tamoxifen is reasonable alternative to adding AC chemotherapy to tamoxifen in premenopausal luminal type node negative breast cancer patients. Citation Format: Heeseung Park, Guiyun Sohn, Byung Ho Son, Jong Won Lee, SeiHyun Ahn. Possibility of GnRH agonist plus tamoxifen as an alternative treatment to AC (adriamycin plus cyclophosphamide) chemotherapy plus tamoxifen treatment in premenopausal hormone responsive HER2 negative breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-09.

Tamoxifen for the prevention of postoperative intra-abdominal adhesions

Postoperative intra-abdominal adhesion (PIAA) is a common complication following abdominal surgeries. Up to now, no practical method or device has been proven to be the gold standard in PIAA formation prevention. This study was designed to evaluate the effects of oral and intraperitoneal tamoxifen citrate on PIAA formation prevention. A total of 48 guinea pigs weighing 300–350 g were included in four groups (12 pigs in each group). Under general anesthesia, laparotomy was performed, and a part of small bowel was abraded using wet gauze so that serosal petechiae developed on the intestinal surface for induction of peritoneal adhesion. In group 1 (control), only this adhesion induction was performed with no treatment. In the second group, 2.5 mg/kg/day tamoxifen citrate was administered by orogastric gavage postoperatively. Group 3 underwent adhesion induction and then intraperitoneal administration of 2.5 mg/kg tamoxifen citrate diluted in 10 ml of aquapura. Group 4, underwent adhesion induction and intraperitoneal administration of 2.5 mg/kg tamoxifen citrate diluted in 10 ml aquapura and then 2.5 mg/kg/day tamoxifen citrate was administered by orogastric gavage postoperatively. Pigs underwent laparotomy on the eighth postoperative day, and grading of adhesions was performed according to the Adhesion Characteristic and Adhesion Tenacity scoring system. Data were analyzed using SPSS for Windows version 16. The control group was significantly different from other groups (p < 0.008), which means usage of tamoxifen (oral or intraperitoneal or both) significantly reduced adhesion formation after laparotomy. Intraperitoneal tamoxifen (group 3) was more effective in prevention of adhesion formation than oral tamoxifen application (group 2; p = 0.006). Also, administration of both oral and intraperitoneal tamoxifen (group 4) reduced adhesions significantly (p = 0.002) in comparison with just oral one (group 2), but it made no difference (p = 0.625) with only intraperitoneal tamoxifen (group 3). This study indicated that tamoxifen significantly reduces PIAAs, and intraperitoneal application is more effective than oral administration. This study shows that preventive effects of intraperitoneal application of tamoxifen will not improve when oral tamoxifen is added postoperatively. More studies with focus on evaluation of probable side effects and also performing clinical trials for evaluating tamoxifen for preventing PIAAs are strongly suggested.

Therapeutic Effect of Silybum marianum Plant Extract on Tamoxifen-Induced Fatty Liver in Rats

Background: Tamoxifen (TMX) is a synthetic drug that is widely used for treatment of breast cancer. Despite the beneficial effects of TMX, the use of this drug has several side effects such as the development of Non-Alcoholic Fatty Liver Disease (NAFLD) in the patients. Silybum marianum is the most researched plant in treatment of liver disease. Objectives: In this study the effect of Silybum marianum Extract (SME) on histological and biochemical parameters in TMX-treated rats was investigated. Materials and Methods: Adult female Wistar rats were divided to four groups; 1) normal control untreated rats, 2) SME-treated rats, that received only SME in a dose of 1.6 g/kg body weight/day, oral gavage for 14 days, 3) TMX-treated rats, that received TMX in a dose of 1 mg/kg body weight/day, subcutaneously, for seven days, 4) TMX-SME-treated rats, that received TMX in a dose of 1 mg/kg body weight/day, subcutaneously, for seven days and then SME by oral gavage for 14 days. The groups were compared in terms of serum glucose, triglyceride, cholesterol, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), High-Density Lipoprotein-Cholesterol (HDL-C), Low-Density Lipoprotein-Cholesterol (LDL-C), total protein and liver triglyceride amount, and histological findings. Results: Concentrations of HDL-C and protein decreased and activity of ALT increased in TMX group compared with the control group. The SME increased protein concentration and decreased ALT activity in TMX-SME group compared with the TMX group. Histopathological examination and triglyceride assay in liver tissues showed lipid accumulation in the TMX-treated rats and amelioration of lipid accumulation in the liver of TMX-SME-treated rats. Conclusions: Intake of water extract of Silybum marianum is a useful treatment for liver function in drug-induced fatty liver.

Aromatase inhibitors, tamoxifen, and endometrial cancer in breast cancer survivors

The risks of both endometrial cancer and postmenopausal breast cancer are increased by obesity and higher endogenous estrogen levels. Although aromatase inhibitors reduce breast cancer incidence, their influence on endometrial cancer is uncertain. The authors investigated this issue in a cohort of 17,064 women who were diagnosed with hormone receptor-positive breast cancer in an integrated group practice health plan. Information on demographics, comorbidities, and the receipt of adjuvant endocrine therapy was available from electronic medical records and pharmacy records, respectively. Endometrial cancer information was obtained from the health plan's Surveillance, Epidemiology, and End Results-affiliated tumor registry, and rates were compared across endocrine therapy groups (aromatase inhibitor, n = 5303; tamoxifen, n = 5155; switchers: both [n = 3787] or none [n = 2819]) using multivariable adjusted Cox proportional-hazards models. Endometrial cancer incidence was a statistically significant 48% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.52; 95% confidence interval, 0.31-0.87; P = .01). Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% confidence interval, 0.37-1.35; P = .30) and 33% lower in the aromatase inhibitor group versus the tamoxifen group (hazard ratio, 0.67; 95% confidence interval, 0.42-1.06; P = .08), but neither difference was statistically significant. Associations were stronger among those with good drug adherence. In a community-based, integrated health plan setting, endometrial cancer incidence was lower in women who were receiving an aromatase inhibitor compared with those who were receiving tamoxifen. In addition, aromatase inhibitors may mitigate the incidence of tamoxifen-associated endometrial cancer. Although there were somewhat fewer endometrial cancers in the aromatase inhibitor group versus the no endocrine therapy group, further studies are needed for the definitive assessment of this potential association.

Effect of varying doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome: an&amp;nbsp;experimental study

ObjectiveTo examine the effects of low-to-high doses of tamoxifen on ovarian histopathology, serum VEGF, and endothelin 1 levels in ovarian hyperstimulation syndrome (OHSS) in an experimental setting.Materials and methodsA total of 20 female Wistar albino rats, 22 days of age, were randomly divided into four groups. Follicle-stimulating hormone 10 IU was administered subcutaneously in 15 rats on 4 consecutive days, with OHSS induction on day 5 by 30 IU of human chorionic gonadotropin. Group 1 (n=5) comprised 35-day-old control rats, group 2 (n=5) 35-day-old OHSS rats, group 3 (n=5) 27-day-old OHSS rats receiving 1 mg/kg of oral tamoxifen for 7 days, group 4 (n=5) 27-day-old OHSS rats receiving 3 mg/kg of oral tamoxifen for 7 days. All rats were decapitated on day 35. Serum VEGF, endothelin 1, and ovarian follicular reserve were assessed in all rats. Kruskal–Wallis variance analysis and the Mann–Whitney U-test were used for statistical comparisons. A Bonferroni correction was performed to control the inflation of significance, with a significance level set at a P-value of less than 0.025.ResultsDespite higher serum VEGF, endothelin 1, follicular reserve, and angiogenesis and fibrosis of the corpus luteum in the OHSS group compared to controls, these differences were not significant (P>0.025, Mann–Whitney U-test). There was a significant reduction in the ovarian follicular reserve in tamoxifen groups compared to controls (P<0.025, Mann–Whitney U-test), while angiogenesis of the corpus luteum, number of atretic follicles, fibrosis, and serum VEGF were significantly higher in rats receiving tamoxifen (P<0.025, Mann–Whitney U-test). Also, significantly lower follicular reserve and fibrosis were observed among rats in the low-dose tamoxifen group in comparison with rats in the high-dose tamoxifen group (P<0.025, Mann–Whitney U-test). No groups had a significant change in endothelin 1 levels (P>0.025, Mann–Whitney U-test).ConclusionTamoxifen 1 g and 3 g resulted in a dose-dependent increase in VEGF and endothelin 1 levels, and ovarian follicle reserves were significantly reduced in our experimental model.

Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer.

The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP) in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF). Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23), a group that received chemotherapy + tamoxifen (n=21), and a group that received only tamoxifen (n=16). Plasma levels of NT-proBNP were assessed at 0 (T0), 6 (T6), and 12 (T12) months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

Adjuvant Ovarian Suppression in Premenopausal Breast Cancer

BackgroundSuppression of ovarian estrogen production reduces the recurrence of hormone-receptor–positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.MethodsWe randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.ResultsAfter a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen–ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen–ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane–ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).ConclusionsAdding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.)

Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats

AimEndothelial dysfunction is considered a premature indication of atherosclerosis and vessel damage and is present in the postmenopausal period. This study compares the influence of estrogen, raloxifene and tamoxifen on factors that affect endothelial function in ovariectomized (OVX) rats. Main methodsThe rats were divided into: SHAM; OVX; OVX+estrogen (0.5μg/kg/day); OVX+raloxifene (2mg/kg/day) and OVX+tamoxifen (1mg/kg/day) groups. The acetylcholine vasorelaxation response was evaluated in the mesenteric vascular bed. The vascular oxidative stress and serum inflammatory cytokine levels were monitored, and analyses of eNOS and iNOS were performed. Key findingsThe acetylcholine-induced responses obtained in the OVX were lower than those obtained in the SHAM, and all treatments restored this response. l-NAME reduced and equalized the acetylcholine-induced response in all groups. The attenuation of the acetylcholine-induced responses by aminoguanidine was greater in the OVX. Endothelial dysfunction in OVX was associated with oxidative stress and an increase in iNOS and decrease in eNOS expression. Except for the production of reactive oxidative species (ROS) in the OVX+tamoxifen, treatments improved the nitric oxide component of the relaxation response and normalized both the oxidative stress and the expression of those signaling pathway enzymes. Serum levels of TNF-α and IL-6 were increased in OVX, and treatments normalized these levels. SignificanceRaloxifene and tamoxifen have similar anti-inflammatory effects that may be important in improving vascular dysfunction. Tamoxifen did not affect the ROS but improved endothelial dysfunction. The protective effect on endothelial function by these treatments provides evidence of their potential cardiovascular benefits in the postmenopausal period.

Low Ovarian Stimulation Using Tamoxifen/FSH Compared to Conventional IVF: A Cohort Comparative Study in Conventional IVF Treatments

Background: Over the last decade, the laboratory procedures in artificial reproduction have improved, thus fewer eggs are necessary. Therefore mild stimulations have been introduced to reduce the risk for the patient and patient drop-outs in treatment. The present study was designed to evaluate the efficacy of low stimulation with Tamoxifen and FSH in a routine IVF clinic. Material and methods: A total of 2,709 regular short antagonist IVF cycles were compared to 170 Tamoxifen low stimulation IVF cycles. All patients were recruited in the same time period and allocated to the different treatments on their own request. Results: No differences in age and number of previous cycles were found in between the groups. The clinical pregnancy rate was found to be significantly lower in the Tamoxifen treated group (20% vs. 26%), however we did not find any significant pregnancy rate following transfer (31% Tamoxifen group vs. 28% in conventional IVF). We found lower numbers of visits, lower costs for medication, less side effects and better acceptance for treatment in the Tamoxifen group. Conclusion: Although we found a lower pregnancy rate per started cycle, the pregnancy rate per transfer was equal and better accepted by the patients.

Effect of tamoxifen and raloxifene on the proliferative activity of the breast epithelium in premenopausal women.

OBJECTIVESTo compare the effects of tamoxifen and raloxifene on the proliferative activity of normal breast tissue in premenopausal women as measured by Ki-67/MIB-1 expression.STUDY DESIGNA total of 48 women with benign breast nodules and a recommendation for surgical removal of the lesion took part in this study. They were randomized to use tamoxifen or raloxifene for 22 days, after which they were submitted to surgery. During the surgical procedure, a 1-cm fragment of normal breast tissue was removed to study Ki-67 expression.RESULTSThe mean percentage ratios between immunolabeled and non-labeled cells were 2.02 ± 1.09 and 3.13 ± 3.23 for the tamoxifen and raloxifene groups, respectively. There was no statistically significant difference between the tamoxifen (n = 16) and raloxifene (n = 14) groups in relation to the immunohistochemical analysis of Ki-67 (P = 0.205).CONCLUSIONThe results of this study showed no difference between tamoxifen and raloxifene with respect to the potential of these drugs to reduce the proliferative activity of the normal breast epithelium in premenopausal women.

Clinical Outcomes of Tamoxifen and Clomiphene Citrate in Intrauterine Insemination Cycles

ABSTRACTBackgroundBoth selective estrogen receptor modulators, tamoxifen and clomiphene have been used for ovulation induction for patients with anovulatory infertility. The aim of this study is to compare the effectiveness of tamoxifen to clomiphene on clinical outcome in intrauterine insemination (IUI) cycles.Materials and methodsIt is a retrospective clinical study. Two hundred and seven women undergoing IUI cycles from July 2013 to July 2014 at Milann—The fertility centre, Bengaluru, India were analyzed. Tamoxifen was administered in the dose of 40 mg starting from day 2/3 of the menstrual cycle for a period of 5 days and clomiphene citrate (CC) was administered in the dose of 100 mg from day 2/3 of menstrual cycle for 5 days. Monitoring of ovulation was done by transvaginal ultrasound from day 5/6 till dominant follicle size was more than 18 mm. Highly purified human chorionic gonadotrophin (hCG) in the dose of 5000 IU was given. Double insemination was done at 24 and 36 hours. Luteal phase support was given in form of dydrogesterone 10 mg twice a day for 14 days. Serum beta-hCG was done after 14 days.ResultIn our study, 76 patients recieved clomiphene citrate (37%) and 126 patients received tamoxifen (62.9%). Both the groups were comparable in terms of age, period of infertility, FSH, LH, antral follicle count and their human menopausal gonadotropin (hMG) requirement (Table 1). Thirteen patients (23.6%) in CC group and 42 patients (76.4%) in tamoxifen group had positive serum beta hCG result. p-value was found to be significant (p = 0.016) (Table 2).ConclusionTamoxifen was associated with better endometrial thickness and pregnancy rate when compared to clomiphene citrate in ovarian stimulation in IUI cycles.How to cite this articleMajeed A, Divyashree PS, Rao KA. Clinical Outcomes of Tamoxifen and Clomiphene Citrate in Intrauterine Insemination Cycles. Int J Infertil Fetal Med 2015;6(3):118-121.

Discovery of Novel DNA Variants in Jordanians Population by Re- Genotyping Affymetrix DMET Arrays Data Using DNA Sequencing

The Affymetrix DMETTMM plus platform (Affymetrix, Santa Clara, CA, USA) is a GeneChip where 1936 SNPs can be genotyped in any given sample at once. The 1936 SNPs were distributed cross 225 genes in the genome. Thirtynine genes on the chip belong to phase I–II drug metabolism, disposition and drug transport gene family. These genes are functional in metabolizing the most widely prescribed anticancer drugs in the world including aromatase inhibitors, tamoxifen and thiopurines groups. In a high-throughput GeneChip array which is based on hybridization with allelespecific probes; genotyping errors are very common which limits the technologies applications; in addition missing calls for many SNPs on the chip immerge as a bigger and more serious problem in high- throughput genotyping methods. This study focuses on re-genotyping these No-call genotypes to maintain sample sizes that are already genotyped by Affymetrix DMETTMM plus platform. Sixty six different variations were identified, 39 of them had No-call genotypes; our re-genotyping resulted in increasing calling rate from 89.08% to 95.56%. Furthermore, Among the variations that were identified, 8 were non-reported: C.-209T > G in UGT2B7 and -698°C > A in CYP1A2 as promoter variants, c.252G > T in SLC22A6 and c.1356T > C in SLC15A1 as silent mutation, c.1277 + 69°C > T and c.1277 + 82°C > T in SLC22A1 as intronic variants associated with each other and the most important variations are two missense (non- synonymous) in NAT2 gene: D20N c.58G > A and G11S c.31G > A. Affymetrix DMETTMM plus platform.

Cognitive functioning during long-term tamoxifen treatment in postmenopausal women with breast cancer.

Endocrine therapy is widely used-often for many years-in women with breast cancer. Yet little is known about cognitive functioning after long-term use of tamoxifen. We examine cognitive sequelae, approximately 3 years after diagnosis, in postmenopausal women with breast cancer who were treated with adjuvant tamoxifen. Data from participants who underwent surgical operation with or without radiotherapy, participants who received adjuvant tamoxifen, and healthy controls were collected. Neuropsychological tests were administered, and participants completed questionnaires on health-related quality of life (Quality of Life Questionnaire Core 30 and Breast Cancer-Specific Quality-of-Life Questionnaire), menopausal symptoms (Functional Assessment of Cancer Therapy-Breast endocrine symptom subscale), and anxiety and depression (Hopkins Symptom Checklist). In total, 107 women participated (adjuvant tamoxifen group, n = 20; surgical operation/radiotherapy group, n = 43; healthy control group, n = 44). Women in the adjuvant tamoxifen group had received tamoxifen for a mean (SD) of 31.5 (18.6) months (range, 15-79 mo) and performed worse on verbal memory than the surgical operation/radiotherapy group (P < 0.05) and the healthy control group (P < 0.05). Participants in the adjuvant tamoxifen group performed worse on measures of fluency than healthy controls (P < 0.05). Furthermore, women in the adjuvant tamoxifen group reported worse cognitive functioning (P < 0.05) than women in the surgical operation/radiotherapy group or the healthy control group. Our results provide insights into cognitive functioning in women who receive long-term adjuvant tamoxifen treatment. By adding the surgical operation/radiotherapy group, we could control for the mental and physical influences of the diagnosis and treatment of breast cancer. Cognitive domains that rely on verbal abilities (verbal memory and fluency) seem to be at risk for deterioration after treatment with tamoxifen.

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial

SummaryBackgroundFour previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation.MethodsIn the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35–70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928.FindingsBetween April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16·0 years (IQR 14·1–17·6), 601 breast cancers have been reported (251 [7·0%] in 3579 patients in the tamoxifen group vs 350 [9·8%] in 3575 women in the placebo group; hazard ratio [HR] 0·71 [95% CI 0·60–0·83], p<0·0001). The risk of developing breast cancer was similar between years 0–10 (226 [6·3%] in 3575 women in the placebo group vs 163 [4·6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0·72 [95% CI 0·59–0·88], p=0·001) and after 10 years (124 [3·8%] in 3295 women vs 88 [2·6%] in 3343, respectively; HR 0·69 [0·53–0·91], p=0·009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0·66 [95% CI 0·54–0·81], p<0·0001) and ductal carcinoma in situ (0·65 [0·43–1·00], p=0·05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1·05 [95% CI 0·71–1·57], p=0·8).InterpretationThese results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention.FundingCancer Research UK (UK) and the National Health and Medical Research Council (Australia).