تاموکسیفن

HER2-positive breast cancer is one of the most aggressive subtypes of breast cancer, accounting for approximately 30% of all diagnosed cases. These cases of cancer are associated with decreased survival, tumor invasion, and overall poor prognosis. Unfortunately, a large number of patients are resistant to conventional treatments. Various reports have shown that tamoxifen has a response rate of 10-15% in estrogen-negative and HER2-positive tumors. The use of natural chemical sensitizers in combination with chemotherapy drugs can provide promising help in cancer treatment by increasing the effectiveness of chemotherapy drugs.

In this study, the chemical sensitization effect of tannic acid with tamoxifen was investigated in SKBR3 cells using real time PCR and flowcytometry tests.

According to the obtained results, it was found that tamoxifen and tannic acid alone cannot significantly reduce the expression level of HER2, but their combination causes a significant decrease in the expression level of EGFR and HER2. Also, the results of flow cytometry showed that the combination of tannic acid with tamoxifen caused a significant increase in the percentage of apoptosis compared to the control group, tamoxifen and tannic acid alone.

In general, it can be concluded that tannic acid can act as a chemical sensitizing polyphenol in combination with tamoxifen and is a promising option for clinical use.

Female infertility is a condition in which despite efforts over a year, they are unable to conceive. The present study was performed aimed to compare the effect of palm pollen herbal regimen (relying on the beneficial properties of date pollen for infertility treatment) with letrozole + tamoxifen drug regimen in the treatment of infertile women.

This double-blind clinical trial study was performed in 2019 on 128 infertile women living in Jahrom city. Subjects were divided into two groups: letrozole + tamoxifen drug regimen and palm pollen herbal regimen. The control group received the letrozole + tamoxifen infertility treatment regimen and the experimental group received a plant-based palm pollen diet in the form of 500 mg capsules 3 times daily from the third day of menstruation. The results were collected based on ultrasound and blood tests. Data were analyzed using SPSS software version 21 and descriptive and inferential statistical tests at the significant level of P <0.05.

The number of follicles, follicle size, endometrial thickness, FSH and LH significantly increased in both control and test groups. But these increases were greater in the control group. However, the results of HCG - test showed that 14 cases (21.87%) in the control group and 10 cases (15.62%) in the experimental group were positive. While HCG - ß with twins was seen in only 4 cases (6.25%) in the experimental group; there were no cases of twins in the control group (P=0.15). There was no significant relationship between pregnancy status between the control and test groups (P> 0.05).

The consumption of palm pollen increases the number and size of follicles and endometrial thickness, although the increase in these factors was less than the group receiving letrozole + tamoxifen, but there was no difference between the two groups in success rate of clinical pregnancy, indicating that this drug combination has the capacity to conduct more extensive research for drug development.

Tamoxifen is a group of drugs of selective estrogen receptor modulators, and is one of the drugs effective in the prevention and treatment of some cancers (such as breast cancer). In this study, the interaction of tamoxifen with DNA is investigated experimentally. Also, the electronic structure (at atomic scale) of the molecular system of tamoxifen was theoretically investigated, using atom in molecule (AIM) theory.

First, in the experimental section of this study, the interaction of Tamoxifen with DNA were investigated by UV-ViS technique and hydrodynamic method (Viscometry). In addition, the analysis of the experimental results shows the obvious effect of concentration on the mechanism of how the tamoxifen molecule binds to DNA. Then, in the theoretical part of this research, using computational biophysical chemistry methods, some properties of tamoxifen molecular system, such as electronic Density of States (DOS), boundary orbital’s energy (HOMO/LUMO), Electrostatic Potential Energy (EPS) and electronic contour maps of the electron density and its Laplacian, will be calculated.

This article is a meta-analysis with animal sample.

 Result of the UV-ViS spectroscopy technique and viscometry indicated hyperchromism and hypochromism effect. In addition, the result were depend on the concentration of the drug and affected the kind of binding of Tamoxifen to DNA. the analysis of computational studies on the drug tamoxifen suggests that the mechanism of the local charge/energy distribution in the molecular system of tamoxifen plays an important role in how this drug binds to DNA.

 Based on the experimental results of UV-ViS technique and viscometry, as well as the electronic/vibrational properties of the tamoxifen molecular system, it was defined that the Tamoxifen interacts significantly with all the binding sites of DNA.

There is a controversial effect of Tamoxifen in reducing breast cancer recurrences, while it may increase the chance of uterine cancer occurrence. In this study, we report a rare case uterine neoplasm shortly after breast cancer treatment.

A 50-year-old woman, gravida 6 live 5 and abortion 1, with history of treated breast cancer referred with the complaint of prolonged abnormal uterine bleeding from one year before. Her breast cancer was treated by surgery and Tamoxifen therapy, which was exchanged to letrozole after her new complaint. Although, no further evaluation had been performed earlier, recently uterine myxoid leiomyosarcoma was defined.

Tamoxifen is one of the most effective drugs in the treatment of breast cancer, but it can increase the risk of uterine cancer. In our case, after taking tamoxifen, she developed uterine leiomyosarcoma. As a result, users of this drug, especially in cases with symptoms such as abnormal bleeding, should be carefully screened for uterine cancer.

Mastalgia is a common complaint among women that requires proper medical treatment. The aim of this study was to investigate the comparison of fluoxetine versus tamoxifen  effects on the mastalgia.

In this clinical trial, 62 women, who referred to surgical clinic of Rafsanjan Ali-Ibn Abi-Talib hospital in 2017, with a complaint of breast pain were selected and treated with fluoxetine or tamoxifen. Correspondingly, informed consent, demographic checklists and the visual scale of the pain were completed in pre-treatment and then 4, 8 and 12 weeks after the treatment.

There was no significant difference between two groups in body mass index, duration of illness and duration of pain (P>0.05). Both fluoxetine and tamoxifen significantly reduced pain (P<0.001), but there was no significant difference between pain reduction in two groups (P>0.05).

Both fluoxetine and tamoxifen were equally effective as alternative therapies against mastalgia

Tamoxifen may have secondary adverse effects on the endometrium. The aim of this study was to investigate the endometrial evaluation in women with breast cancer under tamoxifen therapy with Saline infusion Sonohysterography (SIS).

This cross-sectional study was performed on 40 breast cancer patients under adjutant tamoxifen (20 mg/day for at least 6 months) therapy referred to Amir-al-Momenin hospital in Semnan, Iran, gynecological clinic, by oncologist during 2018 to 2019. Requested data including individual characteristics and results of vaginal sonography, Sonohysterography, Pathology and   hysteroscopy were recorded in checklist.

The mean±SD age of patients was 46.0 ± 6.4 years.  39 patients (97.5%) had amenorrhea. The mean±SD duration of breast cancer was 3.1±1.3 years and the duration of tamoxifen use was 26.3 ± 13.7 months. Sonohysterography was performed without any complication in all patients.  The most important findings in the Sonohysterography were endometrial thickness ≥ 5 mm in 6(15%), echogenic lesion in uterine cavity in 4(10%) and subendometrial cysts in 13 (32.5%) patients. Notably, vaginal sonography found endometrial thickness ≥5 in 16 cases, while Sonohysterography had abnormal findings just in 8 (50%) patients. Overall agreement of Sonohysterography with pathology, hysteroscopy and vaginal sonography was 80%, 80% and 75% respectively.

The findings showed that patients under adjutant tamoxifen therapy are at risk for endometrial pathologies such as polyps and hyperplasia. Sonohysterography is well tolerated and has a good overall agreement with pathologic findings and in comparison with vaginal sonography reduces unnecessary invasive interventions.

PI3K/Akt/mTOR pathway is important in inducing resistance to hormone therapy in patients with hormone positive breast cancer. One regulator of this pathway is the PTEN gene. This study was performed with aim to compare the expression of PTEN gene in hormone receptor positive breast cancer patients between patients with sensitive and resistant to tamoxifen.

This cross-sectional and retrospective study was performed on 80 hormone receptor positive breast cancer patients who had referred to oncology clinics of Mashhad University of Medical Sciences from 2006 to 2016. Tissue samples of tamoxifen-sensitive and -resistant patients (recurrence/metastasis occurring during the first 5 years of adjuvant hormone therapy) were immunohistochemically evaluated for PTEN expression. Data were analyzed by SPSS software (version 16) and Independent t-test, U Mann-Whitney and chi-square tests. P<0.05 was considered statistically significant.

In this study, 80 patients were evaluated in two groups of tamoxifen sensitive and resistant. The expression of PTEN in tamoxifen-sensitive and resistant patients was 97.5% and 27.5%, respectively (p=0.001). However, in patients with more advanced lymph node involvement, the expression of PTEN was significantly reduced (p=0.001), there was no significant relationship between PTEN expression and tumor size (p=0.19), tumor grade (p=0.14) and Her2/neu expression (p=0.85).

There is association between PTEN gene expression and tamoxifen resistance.

Considering the high prevalence of prostate cancer and the effect of androgens on its progression, this study was conducted to investigate the inhibitory effects of tamoxifen as an anti-androgen on prostate cancer. In this experimental study, the human cell line (PC3) was purchased from the Pasteur Institute. The effect of tamoxifen at concentrations of 0, 3.25, 7.5, 15, 30 and 60 μM on cells was evaluated, and the tests of viability, migration, colonization and cell morphological changes were respectively performed using MTT, wound healing, colonization, and giemsa staining methods.
FINDINGS: IC50 dosage of tamoxifen of 15 μM with a regression coefficient of 0.90 was obtained within 24 hours. The results showed that tamoxifen significantly inhibited proliferation with 7.3±0.6 colonies compared with 100 colonies of control (p<0.03) and migration with 278.4±1.5 μm groove diameter compared with 89.68 ± 0.9 μm of control (p<0.01) at the dose of 15 μM. Treatment of cells with a dose of 15 μM also causes changes in the nucleus and cytoplasm and causes apoptosis in comparison with the control group. The results of this study showed that tamoxifen has significant inhibitory effects on PC3 prostate cell and can be considered as an appropriate way for the treatment of prostate cancer.

Exposure to estrogen like chemicals during critical periods of development particularly in the neonatal period can disrupt normal patterns of mammary tissue development later in life. In this study, the effects of neonatal exposure of tamoxifen anti-estrogen and zearalenone mycoestrogen on some histological characteristics of mammary gland in female mouse were investigated.
Twenty newborn female mice of BALB/c strain were divided into four groups: three experimental and one control group (with no treatment). Treatment groups included Tamoxifen (400 μg /kg /day) group, Zearalenone treatment group (2 mg /kg /day) and group treated with tamoxifen췦꭪垧ꉷ treatment group. Daily treatments were started on the first day of life and continued up to 5 subcutaneously. Then about 70 days after birth, mice were deeply anesthetized and the mammary tissue was removed from the body. Following histochemical staining, the samples were studied using light and transmission electron microcopies.
Findings: The result showed that epithelial thickness of milk duct and volume of the nipple in tamoxifen treatment group significantly (pDiscusion & The results of this study show that neonatal administration of tamoxifen probably exerts anti-estrogenic effects and it prevents the normal development of mammary tissue, but zearalenone do not have adverse consequences on mammary tissue.

Tamoxifen is the most commonly used treatment for the patients with breast cancer called ER , which prevents the expression of genes that are effective in the growth and proliferation of cancer cells by estrogen. Resistant to Tamoxifen is a major clinical problem in breast cancer treatment. In recent studies, the role of microRNAs in tamoxifen resistance has been raised through the influence of regulation of cell cycle control genes. Throughout this study, the interactions of microRNAs with genes involved in tamoxifen resistance were investigated.
By comparing the gene expression data in samples of patients sensitive and resistant to Tamoxifen from the GEO database and searching in the database of articles, genes and microRNAs with significant expression variations were determined. Then, by examining the correlation between the expression of genes and microRNAs and bioinformatics by mirwalk software, the interconnection network between the genes and microRNAs was drawn.
The results showed that 21 genes and 62 microRNAs altered in Tamoxifen resistant specimens. With miR342-3P/5P targeting the HOXB13, PRM2, and KLK3 genes, and MiR-520h and miR-582-5p microRNAs, targeting 5 reduced expression genes, can lead to recurrence of breast cancer.
The regulatory network mapped out between a set of genes and microRNAs that are potentially involved in the recurrence of breast cancer treated with Tamoxifen could clarify the role of the microRNAs in the recurrence of breast cancer.

Tamoxifen is steroidal drug, which mainly treats breast cancer and also used to stimulate ovulation. The purpose of the present study was the evaluation of sperm parameters and fertility of mice whose mothers had received tamoxifen during pregnancy.
In this study, 30 female and 15 male mice of NMRI were selected for mating. After mating female mice were randomly divided into two groups, the first group (control) and second group (experimental). All of which contained 15 mice. From the day 13th day of pregnancy, experimental group has received tamoxifen with the dosage of 5 mg/kg for 7 days. After childbirth of the mated mice, male infants were selected. After reaching the age of puberty (6-8Weeks), adult mice were sacrificed by the cervical dislocation. After take sperm, sperm parameters (count, normality and motility), and sperm fertility was performed. In this study SPSS software and statistical t-test was used (p Studies showed that sperm parameters and sperm fertilization were significantly different. The number of sperm in the control group was 83.50±28.20 million, and in the experimental group was 60±14.14 million. There was a decrease in average sperm count in the experimental group compared with the control group (p The results showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility.

Breast cancer is one of the most common cancers in the world that is affected by various genetics, epigenetic and many other environmental factors. Estrogen is one of the risk factors for this cancer. This factor lead to genetic alterations and the beginning and promotion of breast cancer.
In this review, we provide information using databases of NCBI, PubMed, Google Scholar, and Ovid MEDLINE, about the molecular basis of breast cancer, the effect of estrogen hormone, and estrogen receptors on cancer incidence, the use of anti-estrogens such as Tamoxifen in treatment of breast cancer and mechanisms of resistant to these drugs.
Anti-estrogens such as tamoxifen play an important role in treatment of estrogen-receptor positive breast cancers by preventing estrogen binding to its receptors in these tumors. Finding the molecular basis of breast cancer will help us to achieve effective treatment for breast cancer.
Increased estrogen and estrogen receptor highly influence the incidence of breast cancer. Tamoxifen is standard adjuvant therapy for women with ER-positive [], but there is some intrinsic or acquired resistance to endocrine treatment that require further investigations.

The uterus as the major female reproductive organ is particularly vulnerable to environmental and hormonal like compounds. Exposure to estrogen like disrupting chemicals during critical periods of development especially in the neonatal period can have adverse effects on reproduction and fertility later in life. In this study, the effects of neonatal exposure of mycoestrogen zearalenone and anti-estrogen tamoxifen on some histological characteristics of the uterus in female mice were investigated.
Material and 28 newborn female mice of BALB/c strain were divided into four groups (n=7): three experimental and one control group. Treatment Groups included Tamoxifen (400 μg /kg /day) group, group treated with zearalenone (2 mg /kg /day) and group treated with tamoxifen zearalenone. Control mice received no treatment. Daily treatments was started first day of life and continued up to 5 subcutaneously. Then about 70 days after birth in diestrous stage of estrous cycle, mice were deeply anesthetized and uterus was removed from the body. Following histochemical staining, the samples were studied using light and transmission electron microcopies.
The result of this study showed that in between the treatment groups, body weight decreased significantly (P>0.05) in group which received Tamoxifen, compared with control group. Uterus weight increased significantly in Zearalenone group (P>0.05) and Tamoxifen Zearalenone group (P>0.01). Endometrial thickness increased significantly (P>0.05) in group which received Tamoxifen and decreased significantly (P>0.05) in group which received Zearalenone. In addition, myometrial thickness decreased significantly (P>0.05) in group which received Zearalenone compared with control group. The study of electron microscopy showed that the number of cells of uterine luminal epithelial structure increased in the group treated with Tamoxifen compared with control group.
The result of present study indicates that neonatal administration of Tamoxifen and Zearalenone compounds cause histological lesions in uterus structure. Because of the estrogenic nature of zearalenone, the treated neonatal mice with this mycotoxin cause structural abnormalities especially in myometrial structure. On the other hand, Tamoxifen as an estrogenic agonist cause endometrial thickness increase and alterations in the uterus.

Breast cancer is one of the causes of mortality in the world. Half of patients with metastatic extend resistance to Tamoxifen and almost all patients eventually become resistant to tamoxifen. Inorder to counteract with the negative effects of tamoxifen, this drug have been placed in combination with the curcumin. Anti-cancer substance which is less toxic than Tamoxifen. In this study, Diblock (Dendrosome) Nano polymer was used in order to tamoxifen packaging along with curcumin. Anti-cancer efficacy of the obtained compound (Diblock, Tamoxifen and Curcumin) was evaluated in Tamoxifen-resistant (TR) MCF-7 cells and Fibroblast cells.
Material and MTT Assay was used to evaluate anti-proliferation effect and drug toxicity.Flow cytometry and Annexin-V-FLUOS were used inorder to assay anti-proliferation effect and induction of apoptosis, respectively.
Nano-compound has less toxicity effects on normal cells compared with Tamoxifen and increased apoptosis activity and decreased proliferation in MCF-7 cells which are resistant to tamoxifen. Curcumin and Tamoxifen have more apoptotic potential than Tamoxifen alone, Nano-Tamoxifen or Nano-Curcumin.
Results of this study showed that changes in Tamoxifen by curcumin polymeric nanocarrier help to more effective treatment of breast cancer.

Tamoxifen is a nonsteroidal drug which mainly treats breast cancer. It is also applied for stimulation of ovulation and remedy of infertility. Regarding the tamoxifen binding to estrogen receptors and the possible role of estrogens in spermatogenesis, the present study aimed to histologically evaluate spermatogenesis in the seminiferous ducts of mice, whose mothers had received tamoxifen during pregnancy.
In the present study, 30 female and 15 male mice of NMRI race were selected for mating. Since 13th day of pregnancy, the experimental group received tamoxifen with the dosage of 5 mg/kg intra-peritoneally for 7 days, wherease the control group received normal saline. After childbirth of the mated mice, male infants were selected and monitored in the standard laboratory conditions. After reaching the age of puberty (6-8Weeks), adult mice were sacrificed by the cervical dislocation, and the testes were removed for histological evaluation of spermatogenesis. After routine histological processing, the samples were studied by the light microscope.
Histological studies showed that spermatogenic and Sertoli cells in the seminiferous tubules in control and experimental groups were significantly different, though no difference was observed in the number of Leydig cells in the both groups.
The findings of the present study showed that tamoxifen exposure during development can cause histological changes in the seminiferous tubules, which can lead to infertility in the male rat.

Uterine carcinosarcoma، also known as malignant mixed Mullerian tumor، is a rare uterine malignancy. Although the origin and prognosis of this cancer remain undetermined، the Mullerian ducts are believed to be the main origin. This tumor has the ability to change into epithelial and mesenchymal components and is more common among black and postmenopausal women. Prior history of radiation therapy and use of tamoxifen also contribute to this condition. The clinical characteristics of uterine carcinosarcoma، including postmenopausal bleeding، are similar to those of endometrial cancer. This condition with a poor prognosis and aggressive nature may be overcome by a combination of therapies including surgery، chemotherapy، and radiotherapy. Herein، we present a case of uterine carcinosarcoma associated with tamoxifen use in a menopausal patient. CASE REPORT: The patient was a 67-year-old menopausal woman (G9، P5، L5، Ab4)، who underwent lumpectomy and chemoradiotherapy ten years ago due to estrogen receptor-positive breast cancer (ductal carcinoma). The patient received 40 mg of tamoxifen on a daily basis، and after six years of tamoxifen use، she experienced postmenopausal bleeding. Increased endometrial thickness appeared in the ultrasound، and uterine carcinosarcoma was diagnosed، based on pathologic evaluations. The patient received multi-modal therapy، and after a year of follow-up، no specific problems were reported. According to the results، symptoms of uterine cancer should be taken into account in menopausal patients consuming tamoxifen.

One-eighth of women will develop breast cancer in their lifetime, resulting in approximately annual one million women worldwide with breast cancer. Approximately 70% of breast cancers are positive for estrogen receptor alpha (ER-). The presence of ER- receptor is associated with better prognosis and usually indicates that the anti-estrogen drugs such as tamoxifen can be useful in the treatment. Nevertheless, a significant number of ER--positive breast cancers does not respond to tamoxifen. Causes of resistance to tamoxifen and how to sensitize to tamoxifenis not yet known. Preliminary studies indicate that garlic and its derivatives such as allicin, have anti-cancer effects. This study aims to investigate the inhibitory effect of allicin on tamoxifen-sensitive MCF-7 cells. To investigate this theory, the effect of allicin on tamoxifen-sensitive cells (MCF-7), and -resistant cells (Sk-Br-3) in the presence and absence of tamoxifen and 17- estradiol were studied. The cell viability was assessed using MTT assay at 24, 48 and 72 hours. The study revealed that allicin in MCF-7 cells enhances the effectiveness of tamoxifen in the presence and absence of 17-b estradiol. Allicin as an adjunct to tamoxifen can sensitize breast cancer cells to tamoxifen.

Chamomile has several analgesic properties, while the mechanism of these effects in interaction with male sex hormones compared tofemales are not well known. This study aimedto evaluate the analgesic effects of hydro-alcoholic extract of chamomile in male mice, and two phases of femalesexual cycle (diestrus and proestrus) in the presence or absence of estrogen receptors. In this experimental study, adult mice of both genders(weight: 27±3 g) were divided into four groups of control, chamomile recipients (30 or 50 mg/kg), tamoxifen recipients (0.5 or 1 mg/kg), and recipients of combined tamoxifen (1 mg/kg) and chamomile (30 or 50 mg/kg). Drugs were administeredintraperitoneally in one milligram per a kilogram of the body weight, and formalin test was used to induce acute and chronic pain. In addition, cumulative length of foot licking was calculatedin seconds as theindicator of pain perception. In male mice,chamomile extract (30mg/kg) reduced acute pain (53±2, p<0.01)and chronic pain (71±2, p<0.001), and dosage of 50 mg/kgcould reduce acutepain (41±1, p<0.001) and chronic pain (73±2, p<0.001). In diestrus and proestrusfemales, chamomile extract could relieve acute pain at 50 mg/kg (42±2, p<0.05 and 39±1, p<0.05, respectively). As for the chronicphase of pain, chamomile extract (30 mg/kg) was effective in diestrus (72±1, p<0.01) and proestrus (80±2, p<0.001) female mice, whileit could reduce chronic pain at 50 mg/kgindiestrus (59±1, p<0.001) and proestrus (62±2, p<0.001) females. In male mice, the analgesic effects of the extract were more significant.In addition, tamoxifen (1mg/kg)reduced chronic pain in diestrus (81±3, p<0.05) and proestrus (92±2, p<0.05) female mice. In male mice,combination of chamomile (30 mg/kg) and tamoxifen (1mg/kg) decreased acutepain(43±3, p<0.05), andcombination of chamomile (50 mg/kg)and tamoxifen (1mg/kg) reduced acute pain (29±1, p<0.05) and chronic pain (41±2, p<0.01) in male mice. Moreover, the drug combination reduced acutepain (21±1, p<0.001) and chronic pain (44±3, p<0.01)in diestrus females, as well as proestrus ones(19±2, p<0.001) (43±3, p<0.001). According to the results of this study, analgesic effects of chamomile extract are gender-dependent,and these effects are more significant in male mice.Increased analgesic effectsof combinedchamomile and tamoxifen couldbe due to the interaction between estrogenreceptorsand analgesic agents of chamomil.

Treatment of cutaneous leishmaniasis with pentavalent antimony compounds, as an established drug, may have limitations, side effects and recurrence risk. For this reason, finding new and effective drugs is of great importance. In the present study, the effect of tamoxifen on the growth of Leishmania major promastigotes and amastigotes was evaluated in vitro. In this experimental study, the effect of different concentrations (1, 5, 10, 20 and 50 μg/ml) of tamoxifen on Leishmania promastigotes and amastigotes were evaluated in three different times (24, 48 and 72h) and the inhibitory concentration 50 (IC50) was calculated by counting of the parasites. The MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 biphenyltetrazolium bromide) assay was used to determine the percentage of live promastigotes and amastigotes after adding tamoxifen. The number of promastigotes and amastigotes were declined in the presence of various concentrations of tamoxifen after 24, 48 and 72 hours of culturing. Twenty-four hours after culturing, the number of parasites was 1.07×106 per ml in the control group and the parasite numbers in the concentrations of 1 and 50 μg/ml tamoxifen were 0.95×106 and 0.06×106, respectively. The IC50 value of tamoxifen was 2.64μg/ml. Tamoxifen has antileishmanial effects in vitro; thus, more researches on the effect of tamoxifen in animal models are suggested.