Humans ; Female ; Receptors, Estrogen/metabolism* ; Breast Neoplasms/metabolism* ; Receptors, Progesterone/metabolism* ; Immunohistochemistry ; Estrogen Receptor alpha

Estrogen impacts neural development; meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.
Receptors, Estrogen/metabolism* ; Estrogens ; Benzhydryl Compounds/pharmacology* ; Nervous System/metabolism*

Endocrine therapy is one of the primary treatment methods for hormone receptor-positive breast cancer patients. As of June 1 2023, the National Medical Product Administration has approved 56 drugs related to endocrine therapy in patients with HR+ /HER-2- breast cancer (including generic drugs that have passed the consistency evaluation), including 44 endocrine drugs which can be categorized according to their mechanisms of action into selective estrogen receptor modulators, selective estrogen receptor down-regulators, aromatase inhibitors, luteinizing hormone-releasing hormone analogs, and progestogens and 12 targeted drugs for combined with endocrine therapy, including CDK4/6 inhibitors, mTOR inhibitors, and HDAC inhibitors. The different pharmacological characteristics, mechanisms of action, and long-term medication factors of breast cancer endocrine therapy-related drugs can directly affect patients' medication adherence and medication safety. To standardize the pharmaceutical care of endocrine therapy drugs for breast cancer and promote rational use in clinical settings, the Oncology Specialty Pharmacist Subcommittee, in conjunction with multidisciplinary experts nationwide, has developed the "Guidelines for pharmaceutical care of endocrine therapy drugs for breast cancer (2023 edition)". The guidelines is based on clinical evidence-based evidence, relevant regulations of pharmaceutical management, and pharmaceutical care practices. The Delphi method and expert interviews were used to formulate the guidelines. The GRADE approach was used for assessing the certainty of evidence. This guideline mainly focuses on endocrine therapy for HR+ /HER-2- breast cancer patients. Due to space constraints, HER-2 positive targeted drugs were not included in the guideline. It covers 6 dimensions and 22 key problems of pharmaceutical care in the whole process of drug therapy, providing a scientific basis for pharmacists to carry out pharmaceutical care of such drugs.
Humans ; Female ; Breast Neoplasms/drug therapy* ; Aromatase Inhibitors/therapeutic use* ; Receptors, Estrogen

Objective: To investigate the correlation between clinicopathological features and Miller/Payne (MP) grading system of breast carcinoma after neoadjuvant treatment and to establish novel prediction models. Methods: A total of 1 053 cases of invasive breast carcinoma NOS that undertaken neoadjuvant treatment according to Guidelines of CSCO for Breast Cancer were selected at the Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute from September 2016 to September 2019, and the clinical, pathologic data, MP grading and immunohistochemical staining were evaluated. Statistical analysis was conducted using R software. Several novel computer models on prediction of MP grading were established and validated. Results: Among 1 053 patients who accepted neoadjuvant treatment, 316 patients (316/1 053, 30%) were evaluated as MP5 postoperatively, and 737 patients (737/1 053, 70%) did not meet MP5 level. MP5 had significant association with histological grade, ER and PR expression, HER2 status, Ki-67 index and molecular classification (P<0.05). Univariate/multivariate logistic regression analyses further showed that the above clinicopathological features were also independent influencing factors of MP5 grade; five-fold cross-validation was used to evaluate the performance of the models, and the sensitivity and specificity of different models were obtained. Conclusions: MP grading of invasive breast carcinoma NOS after neoadjuvant treatment is associated with high histological grade, negative ER and PR expression, HER2 positivity, high Ki-67 index and molecular classification, which are independent influence factors. GBM model recommended through comparison can provide some help for clinical diagnosis and treatment.
Breast Neoplasms/pathology* ; Female ; Humans ; Ki-67 Antigen/metabolism* ; Neoadjuvant Therapy ; Neoplasm Grading ; Receptor, ErbB-2/metabolism* ; Receptors, Estrogen/metabolism* ; Receptors, Progesterone/metabolism*

BACKGROUND: Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions. METHODS: We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients' demographic profiles and disease characteristics. RESULTS: In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies. CONCLUSIONS The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.
Humans ; Female ; Breast Neoplasms/metabolism* ; Retrospective Studies ; Biomarkers, Tumor/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Receptors, Progesterone/metabolism* ; Receptor, ErbB-2/metabolism* ; Receptors, Estrogen/metabolism* ; Biopsy ; Neoplasm Metastasis

OBJECTIVE: We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients' repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis. METHODS: BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions. RESULTS: A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26-79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., "high-lipid Qi-like microscopic phlegm"), avoidance behavior which unconsciously uses "high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of "high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67). CONCLUSION We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.
Adult ; Aged ; Breast Neoplasms ; Emotions ; Female ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone

OBJECTIVE: To investigate the effect of two different approaches ERRα strategy on the apoptosis in multiple myeloma cell line MM.1S. METHODS: For the one strategy, shRNA was mediated by lentivirus. Stable cell clones were established by transfecting the lentivirus into MM.1S cells and screened by puromycin. For the other strategy, XCT790, a specific reverse agonist of ERRα, was used to treat MM.1S cells. The apoptosis of the cells was analyzed by flow cytometry after ERRα was down-regulated. Western blot assay was used to detect the apoptosis of related proteins. RESULTS: The knocked down ERRα was achieved, lentivirus with shERRα were successfully infected into MM.1S and ERRα was reduced significantly. Knockdown of ERRα could induce MM.1S cell apoptosis dramatically. Meanwhile, the expression of cleaved PARP (a kind of apoptosis related markers) was significantly increased following depletion of ERRα in MM.1S cells. XCT790 could significantly down-regulate the expression of ERRα protein in MM.1S cells, which was consistent with the effect caused by shRNA. CONCLUSION Interference the expression of ERRα by shRNA or XCT790 can induce apparent apoptosis in MM.1S cells, which indicating that ERRα is crucial for the survival of myeloma cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Lentivirus ; Multiple Myeloma ; RNA, Small Interfering/pharmacology* ; Receptors, Estrogen

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with autosomal dominant late-onset non-syndromic hearing loss (NSHL). METHODS: Clinical data of the pedigree were collected. Genomic DNA was extracted from peripheral blood samples of the proband and other family members. Trio whole exome sequencing was carried out for 19 396 genes to identify potential pathogenic variants. Sanger sequencing was carried out to verify the candidate variant in the pedigree. RESULTS: The proband and his father were found to carry a c.1183+1delG p.? variant of the DFNA5 gene. The variant was confirmed to be co-segregating with the disease phenotype in the pedigree. CONCLUSION The c.1183+1delG p.? variant of the DFNA5 gene probably underlay the late onset NSHL in this pedigree. Above finding has enabled accurate genetic counseling for this pedigree.
Age of Onset ; China ; Hearing Loss, Sensorineural/genetics* ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Estrogen/genetics*

Objective To investigate the clinicopathological features and immunohistochemical expression of P504s,E-cadherin,erythroblast transformation-specific related gene(ERG)and estrogen receptor(ER)in prostate adenocarcinoma in Tibet.Methods The clinical data of 15 patients with prostate adenocarcinoma diagnosed by the Department of Pathology of Tibet Autonomous Region People's Hospital from September 2013 to September 2020 were analyzed retrospectively.All patients were assigned to prognostic grade groups based on Gleason score according to the WHO 2016 criteria.Immunostaining of P504s,E-cadherin,ERG,and ER was performed.Results The age of all 15 patients ranged from 61 to 86 years.The serum prostate specific antigen(PSA)concentration was ≥20 ng/ml in 12 patients and<20 ng/ml in 3 patients.Among the 15 patients,11 underwent needle biopsy,1 transurethral resection of the prostate,and 3 radical prostatectomy.Prognostic grouping results revealed 5 cases in grade groups 1-3,4 cases in grade group 4,and 6 cases in grade group 5.Immunohistochemistrically,15 cases(100%)were positive for P504s,E-cadherin and PSA;one case(7%)was positive for ERG;all cases were negative for P63,ER and CK34βE12.Thirteen cases were followed up for 2-48 months,with 2 cases treated with total prostatectomy and 11 cases with non-surgical treatment.Two cases were lost to follow-up. Conclusions Prostate adenocarcinoma is rare relatively in Tibet.The accuracy of diagnosis can be improved by using multiple immunohistochemical markers.The cases of grades 4 and 5 by pathological confirmed are relatively common in Tibet.P504s and E-cadherin are highly expressed in prostate adenocarcinoma patients in Tibet,while ERG presents low expression,ER is unexpressed.
Adenocarcinoma/genetics* ; Cadherins/genetics* ; Child ; Child, Preschool ; Erythroblasts ; Humans ; Male ; Prostate ; Prostatic Neoplasms ; Receptors, Estrogen ; Retrospective Studies ; Tibet ; Transurethral Resection of Prostate

This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERβ expression was detected by immunohistochemistry, and the expression levels of ERβ and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERβ, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERβ and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.
Animals ; Flavonoids ; Hippocampus ; Maze Learning ; Mice ; Polypodiaceae ; Receptors, Estrogen ; Scopolamine/toxicity* ; Signal Transduction ; p38 Mitogen-Activated Protein Kinases/genetics*