Neurological diseases include a variety of neurodegenerative diseases and other brain damage diseases.The treatment schemes for neurological diseases are still in research.The existing clinical and basic studies have confirmed that traditional estrogen therapy has certain protective effect on the nervous system,while it increases the risk of breast or endometrial cancer.The emergence of the selective estrogen receptor modulators (SERMs) can avoid the above mentioned problems.The available studies have confirmed the protective effect of tamoxifen as a SERM on the nervous system.This paper reviews the role and functioning mechanisms of tamoxifen in the nervous system and cognitive function,aiming to provide guidance for the future application of tamoxifen in the treatment of neurological diseases and the improvement of cognitive function.
Tamoxifen/therapeutic use* ; Selective Estrogen Receptor Modulators/therapeutic use* ; Cognition ; Nervous System

BACKGROUND: Breast cancer treatment with selective estrogen receptor modulators (SERMs) increases the incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologic characteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discuss possible pathogenetic mechanisms. METHODS: Among 28,104 patients with breast cancer, clinicopathologic features and incidence of uMMMT were compared between patients who underwent SERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period, incidence, dose, and duration of SERM treatment, as well as overall survival rate, were compared for patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMT vs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathological findings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ, progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT. RESULTS: The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold). All patients with SERM were postmenopausal and received daily 20–40 mg SERM. Cumulative SERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologic features, such as International Federation of Gynecology and Obstetrics stage and overall survival, were not significantly different between patients with S-uMMMT and NS-uMMMT or between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available for immunostaining exhibited strong overexpression/null expression of p53 protein and significantly increased ERβ expression in carcinomatous and sarcomatous components. CONCLUSIONS: SERM therapy seemingly increases risk of S-uMMMT development; however, clinicopathologic features were similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expression might be involved in the etiology of S-uMMMT.
Breast Neoplasms ; Breast ; Desmin ; Estrogens ; Gynecology ; Humans ; Incidence ; Myogenin ; Obstetrics ; Prognosis ; Receptors, Progesterone ; Selective Estrogen Receptor Modulators ; Survival Rate ; Tamoxifen

tamoxifen use was significantly associated with a decreased risk of CIM (p < 0.001). Age of 40 years or higher and the regimens of doxorubicin plus cyclophosphamide followed by docetaxel or paclitaxel were associated with increased risk of TRA (p = 0.001 and p = 0.002, respectively).CONCLUSION: Marked discrepancy in the rates of CIM and TRA was observed in this study. Further, the age-specific frequency of CIM and TRA observed in this study is a reliable and practical estimate of the risks of CIM and TRA in the absence of gonadal protection.]]>
Amenorrhea ; Breast Neoplasms ; Breast ; Cohort Studies ; Cyclophosphamide ; Doxorubicin ; Drug Therapy ; Female ; Gonads ; Humans ; Korea ; Menopause ; Multivariate Analysis ; Paclitaxel ; Retrospective Studies ; Tamoxifen

A 51-year-old woman visited the emergency room with severe abdominal pain of acute onset. She had undergone a breast cancer operation one year previously and had been taking a half-dose (10 mg per day) of tamoxifen for 6 months. She was diagnosed with severe acute necrotizing pancreatitis. She had no other specific underlying disease or medical history. She did not drink alcohol and showed no gallstones on endoscopic ultrasound examination. Her blood triglyceride level had been normal before tamoxifen but had gradually increased to 2,534 mg/dL 6 months after beginning tamoxifen. Tamoxifen was regarded as a very likely causative factor for her necrotizing pancreatitis. After discontinuing the drug and receiving supportive care, she eventually recovered, and her blood triglyceride levels dropped to a normal range. Tamoxifen may be a useful drug for treating breast cancer, but doctors should pay attention to the patient's blood triglyceride level during the medication regimen.
Abdominal Pain ; Breast Neoplasms ; Emergency Service, Hospital ; Female ; Gallstones ; Humans ; Hypertriglyceridemia ; Middle Aged ; Pancreatitis ; Pancreatitis, Acute Necrotizing ; Reference Values ; Tamoxifen ; Triglycerides ; Ultrasonography

PURPOSE: This study was aimed to investigate the combination effect of endoxifen and emodin on estrogen receptor (ER) positive breast cancer cell lines and to explain the mechanism of the combination effect. METHODS: We conducted this study on MCF-7 (ER+/human epidermal growth factor receptor-2 [HER2]−), T47D (ER+/HER2−), ZR-75-1 (ER+/HER2+), and BT474 (ER+/HER2+) cell lines, which confirmed combination effect of endoxifen and emodin. Optimal concentrations for combination were determined to study the effects on proliferation of MCF-7 and ZR-75-1 cells. Analysis of the combination effect was carried out in the CompuSyn software. The combination of downstream mechanisms, and combined effects of other similar compounds were tested on the MCF-7 and ZR 75-1 cell lines. Protein expression was confirmed by western blot. RESULTS: The combination of endoxifen and emodin had antagonistic effects on MCF-7 and ZR-75-1cell lines (combination index > 1). We validated the antagonistic effect in T47D and BT474 cell lines. During the combined treatment, the results showed elevated amounts of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK). Analysis of drug interactions showed antagonistic effect between endoxifen and chemical compounds similar to emodin, such as chrysophanol or rhein, in MCF-7 and ZR-75-1 cells. CONCLUSION: Addition of emodin attenuated tamoxifen's treatment effect via cyclin D1 and pERK up-regulation in ER-positive breast cancer cell lines.
Blotting, Western ; Breast Neoplasms ; Breast ; Cell Line ; Cyclin D1 ; Drug Interactions ; Emodin ; Epidermal Growth Factor ; Estrogens ; Phosphotransferases ; Phytoestrogens ; Tamoxifen ; Therapeutic Uses ; Up-Regulation

PURPOSE: Breast cancer (BC) is one of the most common malignancies globally, and millions of women worldwide are diagnosed with BC every year. Up to 70% of BC patients are estrogen receptor (ER)-positive. Numerous studies have shown that tamoxifen has a significant therapeutic effect on both primary and metastatic ER-positive BC patients. Although tamoxifen is currently one of the most successful therapeutic agents for BC, a significant proportion of patients will eventually become resistant to tamoxifen, leading to tumor recurrence and metastasis. Knowledge about the development of tamoxifen resistance in BC patients is still limited. METHODS: We applied a loss-and-gain method to study the biological functional role of cell division cycle associated 8 (CDCA8) in tamoxifen resistance in BC cells. RESULTS: We found that CDCA8 was significantly elevated in tamoxifen-resistant BC cells. Knockdown of CDCA8 expression significantly inhibited the proliferation of tamoxifen-resistant BC cells and reduced their resistance to tamoxifen. In contrast, overexpression of CDCA8 promoted the growth of tamoxifen-sensitive BC cells and induced their resistance to tamoxifen. CONCLUSION: In this study, we reported that CDCA8 is a key regulator of tamoxifen resistance in BC, suggesting that CDCA8 may serve as a potential therapeutic target for BC treatment.
Apoptosis ; Breast Neoplasms ; Breast ; Cell Cycle ; Cell Division ; Estrogens ; Female ; Humans ; Methods ; Neoplasm Metastasis ; Recurrence ; Tamoxifen

PURPOSE: The extension of endocrine therapy beyond 5 years for recurrence-free survivors of breast cancer improves survival; however, the issue on how to clinically identify appropriate candidates remains controversial. This study aimed to identify prognostic factors for breast-cancer-specific mortality in patients who have had 5 years of tamoxifen treatment and categorize subgroups based on the risk of death using combinations of these prognostic factors to assist in the clinical decision to perform further endocrine therapy. METHODS: In total, 3,158 patients with breast cancer were enrolled. Breast cancer-specific survival rates after 5 years of tamoxifen treatment were calculated, and associated prognostic factors were analyzed using a Cox proportional-hazards model. RESULTS: An age extreme at diagnosis (i.e., < 40 or ≥ 60 years), tumor size > 2 cm, and positive lymphovascular invasion were robust independent prognostic factors for late breast cancer-specific death in tamoxifen-treated patients (hazard ratio [HR] = 2.162, 1.739, and 1.993; p = 0.001, 0.047, and 0.011, respectively). Lymph node metastasis and progesterone receptor negativity had borderline significance in this regard (HR = 1.741 and 1.638, p = 0.099 and 0.061). The study patients were classified into four groups according to the number of prognostic indicators, i.e., low, intermediate, high, and extremely high risk. The additional 5- and 10-year cumulative risks of breast cancer-specific death were 0.8% and 1.5% in the low-risk group, 0.9% and 3.9% in the intermediate-risk group, 1.3% and 7.3% in the high-risk group, and 4.8% and 13.8% in the extremely high-risk group, respectively. CONCLUSION: This new risk stratification system for late mortality in breast cancer can be used to identify the right candidates for extended endocrine therapy after 5 years of tamoxifen treatment.
Breast Neoplasms ; Breast ; Diagnosis ; Humans ; Lymph Nodes ; Mortality ; Neoplasm Metastasis ; Prognosis ; Receptors, Progesterone ; Survival Rate ; Survivors ; Tamoxifen

OBJECTIVES: To uncover gynecologic conditions with similar transvaginal sonographic findings of thick uterine endometrium with honeycomb appearance in pre-and postmenopausal women.METHODS: We retrospectively reviewed cases of patients with endometrial tissue biopsy from January 2010 to December 2016. We also collected office flexible hysteroscopic findings and surgical pathologic results. We analyzed data from 393 patients with confirmed endometrial pathology. Among these patients, 69 had transvaginal ultrasonographic images with thick uterine endometrium and honeycomb or “Swiss cheese” appearance.RESULTS: We found gynecologic conditions such as submucosal leiomyoma with degeneration, endometrial polyp, pseudocystic endometrial change associated with tamoxifen use, progesterone associated endometrial change, pyometra, retained placenta, and uterine synechiae manifested with similar thick endometrium with “Swiss cheese” appearance in transvaginal sonographic images. The most common diagnosis in postmenopausal women was atrophic endometritis, followed by endometrial cancer and endometrial polyps. The most common diagnosis in premenopausal women was abnormal uterine bleeding without pathologic conditions.CONCLUSIONS: Sonographic findings of thick uterine endometrium with “Swiss cheese” appearance need to be considered together with a thorough review of the patient's history and chief complaint before making a tentative diagnosis due to the various conditions sharing the feature.
Biopsy ; Diagnosis ; Endometrial Neoplasms ; Endometritis ; Endometrium ; Female ; Gynatresia ; Humans ; Hyperplasia ; Leiomyoma ; Menopause ; Pathology ; Placenta, Retained ; Polyps ; Progesterone ; Pyometra ; Retrospective Studies ; Tamoxifen ; Ultrasonography ; Uterine Hemorrhage

Male breast cancer (MBC), which constitutes only 1% of all breast cancer cases worldwide, is associated with mutations in the BRCA1 and BRCA2 genes, Klinefelter’s syndrome and a positive family history of breast or ovarian malignancy. Patients with MBC typically present with a palpable subareolar mass, with or without nipple involvement. MBC can be identified by mammography and/or ultrasonography. The definitive diagnosis is made through core needle biopsy and cytology. Breast cancer in men are typically low-grade, and usually estrogen- and progesterone-receptor positive. The surgical treatment of choice is usually a modified radical mastectomy. Hormone therapy, can be used as first-line treatment for hormone-receptor positive MBC, and as adjuvant or palliative therapy for advanced cases. The use of adjuvant cytotoxic chemotherapy has been shown to reduce cancer recurrence and improve overall survival. We present the case of a 51-year-old male who came in due to an enlarging right breast mass that had been removed twice in the past eight years. We were able to establish that the patient had MBC, for which he subsequently underwent a modified radical mastectomy
Klinefelter Syndrome ; Mastectomy, Modified Radical ; Tamoxifen x

OBJECTIVETo explore the effects of electroacupuncture (EA) at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency (POI).

METHODSA total of 48 SD female rats with regular estrus were divided into a blank group (=8), a model group (=10), an EA group (=10), a binding group (=10) and a tamoxifen (TAM) group (=10). The rats in the model group, EA group, binding group and TAM group were all treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 15 consecutive days to establish the model of POI; the rats in the blank group were treated with normal diet. After the model was established successfully, the rats in the EA group were treated with EA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) with continuous wave (1 to 3 Hz, 0.1 to 1 mA) for 20 minutes, once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the TAM group were treated with subcutaneous injection of tamoxifen (1mg/kg), once a day (five times a week) for the first two weeks and once every other day (three times a week) for the following two weeks. The rats in the binding group were bound by a small sack as the EA group. The rats in the blank group and the model group were treated with normal diet. After four weeks, the sexual gland weight and index were tested in each group; the ELISA method was applied to test the level of anti-mllerian hormone (AMH) and inhibin B; the morphology of ovary was observed; the number of primordial follicles, primary follicle, antral follicle and atretic follicle was counted; the expression of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-1 receptor (IGF-1R) were measured.

RESULTS(1) Compared with the blank group, the ovary weight, ovary index, uterus weight and uterus index were significantly decreased after treatment in the model group, EA group, binding group and TAM group (all <0.01); but the differences between the model group and the EA group, binding group, TAM group were not significant (all >0.05). (2) Compared with the blank group, the levels of serum AMH, inhibin B and E were significantly reduced; the levels of FSH and LH were significantly increased in the model group; EA group, binding group and TAM group (all <0.01). Compared with the model group, the levels of serum AMH, inhibin B and E were significantly increased, the level of FSH and LH were significantly reduced in the EA group and TAM group (all <0.01). (3) Compared with the blank group, in the model group, EA group, binding group and TAM group the ovary was dark red and pale, surrounded by particle or not; the morphology was small and atrophic; the primordial follicles was reduced even vanished; the structure of primary follicle was damaged and loosely arranged; the mature follicle was few; the atretic follicle and interstitial gland were increased. (4) Compared with the blank group, the expressions of IGF-1 mRNA and IGF-1R mRNA were increased in the model group (all <0.01); compared with the blank group, the expression of IGF-1 mRNA was increased in the binding group (<0.05), but that of IGF-1R mRNA was not significantly different (>0.05); compared with the model group, the expression of IGF-1 mRNA was not significantly different in the EA group, binding group and TAM group (all >0.05), but that of IGF-1R mRNA was reduced (<0.05, <0.01).

CONCLUSIONEA at "Zhongliao" (BL 33) and "Tianshu" (ST 25) has improvement effect on ovarian function in rats with VCD-induced POI, which is likely to be related to regulating the IGF-1R mRNA expression to improve the IGF-1/ IGF-1R axis.

Acupuncture Points ; Animals ; Electroacupuncture ; Female ; Insulin-Like Growth Factor I ; metabolism ; Primary Ovarian Insufficiency ; chemically induced ; therapy ; Rats ; Rats, Sprague-Dawley ; Receptor, IGF Type 1 ; metabolism ; Tamoxifen ; pharmacology