A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy

SUMMARY OBJECTIVE: The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS: Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS: A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION: In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.

Prognostic influencing factors analysis of patients with estrogen receptor-positive de novo stage Ⅳbreast cancer / 肿瘤研究与临床

Objective:To investigate the factors influencing the prognosis of patients with estrogen receptor (ER)-positive de novo stage Ⅳ breast cancer.Methods:The clinical data of 339 patients with ER-positive de novo stage Ⅳ breast cancer treated in Tianjin Medical University Cancer Hospital and Cangzhou Hospital of Integrated TCM-WM from February 2010 to December 2017 were retrospectively analyzed. Related factors such as age, time of chief complaint, the clinical T/N stage, site of metastasis, expressions of molecular markers and treatment mode were included. Univariate log-rank test and multivariate Cox regression model were used to analyze the effects of prognostic factors on patients' overall survival (OS).Results:Univariate analysis showed that there were statistically significant differences in the OS of patients stratified by clinical N stage at first diagnosis, metastasis sites at first diagnosis, ER expression, progesterone receptor (PR) expression, Ki-67 positive index and p53 expression, endocrine therapy, chemotherapy at first diagnosis, surgery and radiotherapy of the primary lesions (all P < 0.01). Multivariate Cox regression analysis results showed that metastasis sites at first diagnosis, Ki-67 positive index, surgery and radiotherapy of the primary lesions were all independent influencing factors of OS for breast cancer patients (all P < 0.01). Conclusions:Patients with ER-positive de novo stage Ⅳ breast cancer have a good prognosis when they have oligometastasis, Ki-67 positive index ≤ 20%, and they receive surgery and radiotherapy of the primary lesions.

Research progress on the mechanism of endocrine therapy resistance for breast cancer / 国际肿瘤学杂志

Endocrine therapy resistance is a major challenge in the treatment of hormone receptor-positive breast cancer. In recent years, endocrine resistance mechanisms have focused on ESR1 mutations or fusions, epigenetic regulation, abnormal regulation of signal transduction pathway, cell cycle regulation, cancer stem cells, metabolic reprogramming, tumor microenvironment and autophagy. Exploring the latest advances in the mechanisms of endocrine therapy resistance in breast cancer may provide more research ideas and treatment options for the precision treatment of hormone receptor-positive breast cancer.

Expression and clinical significance of estrogen receptor, progesterone receptor, p53 and p16 protein in endometrial carcinoma / 中国基层医药

Objective:To investigate the expression and clinical significance of estrogen receptor (ER), progesterone receptor (PR), p53 and p16 protein in endometrial carcinoma.Methods:The endometrial tissue of 57 patients with endometrial carcinoma who received surgery in The First People's Hospital of Chuzhou between January 2017 and May 2021 was harvested as the study group. The normal endometrial tissue of 30 patients with endometrial hyperplasia was selected as the control group. Envision immunohistochemical staining was performed to determine the expression of ER, PR, p53 and p16 protein in endometrial tissue and analyze their expression with clinical pathological characteristics.Results:ER, PR, p16 protein expression rates in the endometrial tissue in the study group were 70.2%, 61.4%, 38.6%, respectively, which were significantly lower than 90.0%, 86.7%, 93.3% in the control group ( χ2 = 4.36, 5.98, 24.09, all P < 0.05). p53 expression rate in the endometrial tissue was significantly higher in the study group than that in the control group (52.6% vs. 13.3%, χ2 = 12.75, P < 0.001). ER and PR expression were significantly different between endometrial carcinoma patients with lymph node metastasis and those without and among those with different histological grades and those at different pathological stages (all P < 0.05). There was no significant difference in p53 protein expression among patients with different pathological stages of endometrial carcinoma, between patients who suffered endometrial carcinoma at different ages, and between patients with different degrees of myometrial invasion (all P > 0.05). p16 protein expression rate differed among patients with different pathological stages of endometrial carcinoma, among those with different histological grades and between patients with different degrees of myometrial invasion (all P < 0.05). There was no significant difference in p16 protein expression rate between endometrial carcinoma patients with lymph node metastasis and those without ( P > 0.05). Conclusion:Abnormal expressions of ER, PR, p53 and p16 protein in endometrial tissue may be related to the occurrence, development and transformation of the disease. Combined detection of ER, PR, p53 and p16 protein is helpful for the clinical diagnosis, treatment and prognosis assessment of endometrial carcinoma.

Características clínico-tumorales de las pacientes diabéticas con cáncer de mama / Clinical and tumoral characteristics of diabetic patients with breast cancer

RESUMEN Introducción: el cáncer de mama presenta una alta incidencia; sus características y asociación a otras comorbilidades suscita el interés de la comunidad científica Objetivo: identificar la relación entre características clínico, tumorales y moleculares con la diabetes mellitus en pacientes con cáncer de mama. Métodos: se realizó un estudio observacional, analítico y transversal en pacientes con cáncer de mama atendidas en el Centro de Atención al Paciente Oncológico "Tercer Congreso" en el período comprendido entre 2016-2021. El universo estuvo constituido por 116 pacientes. La información se extrajo de las historias clínicas. Resultados: se identificó asociación entre la edad de 50 años o más, la presencia de hipertensión arterial y el antecedente de cardiopatía isquémica con la presencia de diabetes mellitus (p<0,05). Se encontró predominio de pacientes con tumores entre 2 y 5 cm (59,48 %), con mayor incidencia en las diabéticas (90 %). La presencia de diabetes mellitus se asoció al tamaño del tumor (p<0,001), ganglio linfático metastásico (p<0,001), y los subtipos receptores de estrógeno y receptor 2 del factor de crecimiento epidérmico humano. En las pacientes diabéticas la media de diámetro mayor tumoral fue de 2,45 ± 0,7, superior a las no diabéticas. Conclusiones: en las pacientes con cáncer de mama, la presencia de diabetes mellitus se asoció al tamaño del tumor, los ganglios linfáticos metastásicos, así como a subtipos moleculares relacionados al receptor de estrógeno y receptor 2 del factor de crecimiento epidérmico humano. Las pacientes diabéticas presentaron un diámetro mayor tumoral superior.

ABSTRACT Introduction: breast cancer has a high incidence; its characteristics and association with other comorbidities arouse the interest of the scientific community. Objective: to identify the relationship among clinical, tumoral and molecular characteristics with diabetes mellitus in patients with breast cancer. Methods: an observational, analytical and cross-sectional study was conducted in patients with breast cancer attended Tercer Congreso Cancer Treatment Center in the period 2016-2021. The target group consisted of 116 patients. The information was collected from the medical records. Results: an association was identified between the ages of 50 or older, the presence of hypertension and a history of ischemic heart disease with the incidence of diabetes mellitus (p<0,05). There was a predominance of patients with tumors between 2 and 5 cm (59,48 %), with a higher prevalence in diabetic women (90 %). The presence of diabetes mellitus was associated with tumor size (p<0,001), metastatic lymph node (p<0,001), with estrogen receptor and human epidermal growth factor receptor 2 subtypes. In diabetic patients the mean tumor diameter was 2,45 ± 0,7, higher than in non-diabetic patients. Conclusions: in patients with breast cancer, the presence of diabetes mellitus was associated with tumor size, metastatic lymph nodes, as well as with molecular subtypes related to estrogen receptor and human epidermal growth factor receptor 2. Diabetic patients had a larger tumor diameter.

Immunohistochemical and clinicopathologic features of estrogen receptor-negative, progesterone receptor-positive, HER-2 negative breast carcinomas

SUMMARY OBJECTIVE: Currently, there is an ongoing debate whether progesterone receptor positive and estrogen receptor negative breast carcinomas represent a true distinct subtype of tumor or a mere immunohistochemical artifact. In this study, we conducted an immunohistochemistry panel with the antibodies TFF1, EGFR, and CK5 to reclassify this phenotype in a luminal or basal-like subtype. METHODS: Tumors estrogen receptor -/progesterone receptor +, Her-2 - from a large population of breast cancer patients were selected to be studied. Immunohistochemistry with the antibodies TFF1, EGFR, and CK5 was performed. Tumors showing positivity for TFF1, regardless of EGFR and CK5 results, were classified as luminal-like carcinomas. Those lesions that were negative for TFF1, but were positive for EGFR and/or CK5, were classified as basal-like triple-negative carcinomas. When the three markers were negative, tumors were classified as undetermined. Clinical pathologic characteristics of patients and tumor recurrence were evaluated. RESULTS: Out of 1188 breast carcinomas investigated, 30 cases (2.5%) presented the estrogen receptor -/progesterone receptor +/HER2- phenotype. Of them, 27 tumors (90%) were classified as basal-like triple-negative carcinomas, one as luminal-like (3.3%), and two as undetermined tumors (6.7%). The mean follow-up for the study group was 27.7 (2.7 to 50) months. Out of the 26 patients, 6 had cancer recurrence: 2 local and 4 systemic recurrences. The average time for recurrence was 17 (8 to 38) months. CONCLUSION: Estrogen receptor -/progesterone receptor +/tumors exhibit aggressive behavior, similar to triple-negative tumors. An appropriate categorization of these tumors should be made to improve their therapeutic management.

Consensus recommendations for the clinical application of CDK4/6 inhibitors in patients with hormone receptor positive, human epidermal growth factor receptor 2 negative advanced breast cancer / 中华肿瘤杂志

The introduction of cyclin-dependent kinase (CDK) 4/6 inhibitors has revolutionized the clinical management paradigm of hormone receptor (HR) positive/human epidermal growth factor receptor (HER) 2 negative breast cancer. As of today, CDK 4/6 inhibitors including Palbociclib, Ribociclib, and Abemaciclib have been widely approved by regulatory agencies. Randomized clinical trials demonstrated that CDK 4/6 inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant in the first-, second- or later-line setting for HR positive/HER2 negative locally advanced or metastatic breast cancer led to substantial reduction in the risk of disease progression or death. Adverse effects of treatment were manageable and as or better than expected in terms of patient satisfaction. Considering CDK4/6 inhibitors in combination with endocrine therapy being a novel approach in China clinical practice, the panel developed the consensus comprehensively describing the pharmacology properties, monitoring strategy during treatment and adverse events management, to facilitate greater understanding in Chinese oncologists of a whole new therapeutic class of drug, promote accuracy of clinical decision and help reach the ultimate goal of improving survival and quality of life of the target patient population.

Mechanism of action of estrogen and its receptor in the development and progression of nonalcoholic fatty liver disease / 临床肝胆病杂志

The incidence rate of nonalcoholic fatty liver disease (NAFLD) has increased sharply, and there is still a lack of effective pharmacotherapy at present. Although great achievements have been made in the research on the pathogenesis of NAFLD, we still do not know enough about the gender differences of NAFLD. As an important sex hormone, estrogen affects the development and progression of NAFLD by regulating mood and energy homeostasis, adipose tissue function and distribution, inflammatory response, insulin resistance, liver fat accumulation, and liver immunity. An adequate understanding of the mechanism of action of estrogen and its receptor in NAFLD may provide new ideas for the treatment of NAFLD.

Analysis of the correlation of PELP1/MNAR expression with expressions of estrogen receptor, human epidermal growth factor receptor 2, Ki-67 and PIK3CA gene mutation in invasive breast cancer / 肿瘤研究与临床

Objective:To investigate the correlation of PELP1/MNAR expression with expressions of estrogen receptor (ER), Ki-67, human epidermal growth factor receptor 2 (HER2) and PIK3CA gene mutation.Methods:A total of 80 paraffin-embedded tissue specimens of primary invasive breast cancer patients in the Fifth People's Hospital of Datong in Shanxi Province from January 2008 to December 2018 were collected. The expression of PELP1/MNAR was examined by immunohistochemistry EliVision tow-step method. The polymerase chain reaction (PCR)-Sanger sequencing method was used to detect the mutation of PIK3CA gene. The expressions of PELP1/MNAR among patients with different expression status of ER, Ki-67, HER2 and with or without PIK3CA gene mutation were compared, and the correlations between each index and the expression of PELP1/MNAR were analyzed.Results:The high expression rates of PELP1/MNAR protein in patients with ER-positive [86.1% (31/36) vs. 59.1% (26/44)], Ki-67 high expression [100.0% (13/13) vs. 65.7% (44/67)], HER2-positive [81.0% (34/42) vs. 60.5% (23/38)] were high, and the differences were statistically significant (all P<0.05). There was no significant difference in the high expression rate of PELP1/MNAR protein between patients with mutant and wild-type PIK3CA [60.0% (12/20) vs. 75.0% (45/60), P = 0.199]. The expression of PELP1/MNAR was negatively correlated with the expression level of ER ( r = -0.195, P < 0.05), positively correlated with the expression level of Ki-67 ( r = 0.198, P < 0.05), positively correlated with the expression level of HER2 ( r = 0.225, P < 0.05), and negatively correlated with lymph node metastasis ( r = -0.269, P < 0.05). Conclusions:The expression of PELP1/MNAR in invasive breast cancer is negatively correlated with the expression level of ER, and positively correlated with the expression level of Ki-67 and HER2. There is no correlation between PELP1/MNAR expression and PIK3CA gene mutation, and the two may play their own role in the PI3K-AKT-mTOR regulatory pathway of breast cancer.

Survival rates of advanced estrogen-receptor positive breast cancer. Analysis of 211 cases

ABSTRACT Background: About 80% of breast cancer (BC) cases express estrogen receptor (ER), which has been correlated with good prognosis and response to estrogen deprivation Aim: To characterize ER positive advanced BC (ABC) patients treated at our institution assessing the impact of clinical pre-sentation (stage IV, de novo disease at diagnosis versus systemic recurrence) and BC subtype on survival rates. Material and Methods: We evaluated 211 ER+ advanced BC (ABC) patients, treated between 1997 and 2017. Results: The median overall survival (OS) was 37 months. Median OS for the period 1997/2006 and 2007/2017 were 33 and 42 months, respectively (p = 0.47). Luminal A, ABC stage IV disease at diagnosis displayed better OS rates than Luminal B stage IV tumors (100 and 32 months respectively, p < 0.01). Conclusions: Clinical presentation (stage IV vs. systemic recurrence) and tumor subtype are key determinants of OS in ABC.

Antecedentes: Casi el 80% de los casos de cáncer de mama (CM) son positivos para receptores de estrógenos (RE+). Éstos se caracterizan por una mejor sobrevida y respuesta a terapia endocrina. Objetivo: Caracterizar a pacientes con CM avanzado (CMA), RE+, y determinar sobrevida según presentación clínica y subtipos. Material y Métodos: Analizamos en nuestra base de datos los antecedentes de 211 pacientes con CMA RE+, tratados en nuestra institución en el período 1997-2017. Se evaluó el impacto de la presentación clínica (estadio IV al diagnóstico, enfermedad de novo, versus recurrencia sistémica) y subtipo de CM, en los niveles de sobrevida. Resultados: La mediana de sobrevida global (SG) fue de 37 meses. La mediana de SG para el período 1997/2006 y 2007/2017 fue de 33 y 42 meses; respectivamente (p = 0,47). Pacientes con CMA, estadio IV, Luminal A al momento del diagnóstico mostraron mejores tasas de SG frente al estadio IV del Luminal B (100 y 32 meses respectivamente (p < 0,01). Conclusiones: La presentación clínica (estadio IV, de novo, versus recurrencia sistémica) y subtipo son determinantes clave de la SG en CMA.

Association of ESRα XbaI A > G, ESRα PvuII T > C and ESRβ AlwNI T > C Polymorphisms with the Risk of Developing Adolescent Idiopathic Scoliosis: A Systematic Review and Genetic Meta-analysis / Associação dos polimorfismos ESRα XbaI A > G, ESRα PvuII T > C e ESRβ AlwNI T > C com o risco de desenvolver escoliose idiopática da adolescência: Revisão sistemática e metanálise genética

Abstract Several association studies of genes polymorphisms on estrogen receptors-α and β with respect to adolescent idiopathic scoliosis (AIS) have been published in the past two decades. However, the association with AIS, especially among different ethnic subgroups, still remains controversial. Thus, we investigated these inconclusive data by performing a meta-analysis to systematically evaluate the association. A literature search was conducted in the PubMed, ISI Web of Science, EMBASE, SCOPUS, EBSCO, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang databases until January 20, 2018. The strength of relationship was assessed using odds ratios (ORs) and 95% confidence intervals (95%CIs). A total of 12 case-control studies with 4,304 cases of AIS and 3,123 controls met our criteria. The pooled ORs indicated that the ESRα XbaI A > G, ESRα PvuII T > C and ESRβ AlwNI T > C polymorphisms were not significantly associated with the risk of developing AIS in the overall analysis. However, we found a significant association between the ESRα XbaI A > G polymorphism and AIS under the homozygote model (GG versus AA; OR = 1.448, 95%CI: 1.052-1.993; p = 0.023). The present meta-analysis suggests that the ESRα XbaI A > G, ESRα PvuII T > C and ESRβ AlwNI T > C polymorphisms may not be associated with the risk of developing AIS in the overall analysis. However, ESRα XbaI A > G might have an influence on the susceptibility to develop AIS among Asians. Considering the limited sample size and ethnicity, further larger studies are needed to provide a more precise estimation of the associations.

Resumo Vários estudos de associação entre os polimorfismos genéticos nos receptores α e β de estrogênio e a escoliose idiopática da adolescência (EIA) foram publicados nas últimas duas décadas. No entanto, a associação com a EIA, especialmente em diferentes subgrupos étnicos, continua a ser controversa. Assim, o presente estudo investigou esses dados inconclusivos por meio de uma metanálise para avaliar sistematicamente essa associação. Uma pesquisa bibliográfica foi realizada nas bases de dados PubMed, ISI Web of Science, EMBASE, SCOPUS, EBSCO, Cochrane Library, China National Knowledge Infrastructure (CNKI) e Wanfang até 20 de janeiro de 2018. A força de associação foi avaliada por meio de razões de probabilidades (RPs) e intervalos de confiança de 95% (ICs95%). Um total de 12 estudos de caso-controle, com 4.304 casos de EIA e 3.123 controles, atenderam aos critérios de inclusão do presente estudo. As RPs combinadas indicaram que os polimorfismos ESRα XbaI A > G, ESRα PvuII T > C e ESRβ AlwNI T > C podem não estar significativamente associados ao risco geral de desenvolvimento de EIA. No entanto, observou-se uma associação significativa entre o polimorfismo ESRα XbaI A > G e a EIA sob o modelo homozigótico (GG versus AA; RP = 1,448; IC95%: 1,052-1,993; p = 0,023). Esta metanálise sugere que os polimorfismos ESRα XbaI A > G, ESRα PvuII T > C e ESRβ AlwNI T > C podem não estar associados ao risco geral de desenvolvimento de EIA. No entanto, ESRα XbaI A > G pode influenciar a suscetibilidade de desenvolver EIA entre indivíduos asiáticos. Considerando o tamanho e a variação étnica limitada da amostra, outros estudos de maior escala são necessários para obter uma estimativa mais precisa das associações.

Incidencia de mutaciones genéticas en pacientes con cáncer de mama y ovario con patrón de origen hereditario / Incidence of genetic mutations in patients with breast cancer and ovarian cancer with hereditary pattern

Resumen OBJETIVO: Determinar las mutaciones genéticas en el cáncer de mama de patrón hereditario y demostrar si existe alguna asociación significativa entre las más comunes en población mexicana y el riesgo de padecerlo. MATERIALES Y MÉTODOS: Estudio transversal y observacional efectuado en el Hospital Ángeles México en coordinación con el Instituto Nacional de Medicina Genómica. Criterios de inclusión: pacientes con cáncer de mama y uno o más familiares de primer grado afectados por esta enfermedad y pacientes con cáncer de ovario. Criterios de exclusión: pacientes sin antecedentes de cáncer de mama ni ovario, o con algún familiar en el protocolo. Se empleó la técnica de rearreglos en placas RT2 Profiler para Master-Mix Quantinova probe PCR kit. Para el análisis estadístico se utilizó el programa SPSS versión 22 y Epi Info versión 7. RESULTADOS: Se estudiaron 39 pacientes con edad promedio de 53.2 ± 12.1 años. Los receptores de progesterona y estrógeno no mostraron diferencia entre grupos. Hubo mayor tendencia para BRCA1. Al estudiar las mutaciones con significación estadística, en las que sobresalieron los casos de BRCA2 versus sin significación y los casos negativos, no hubo diferencia estadística significativa, pero con una tendencia a mayor frecuencia de BCRA1. Al evaluar las estirpes de cáncer de mama y los grados nucleares comparados por edad, los tres grupos de grado nuclear comparados por edad mostraron diferencias. CONCLUSIÓN: Los datos obtenidos muestran que en la población mexicana el gen BRCA2 es el de mayor incidencia de cáncer hereditario, en edad de aparición más temprana y mayor grado nuclear al momento del diagnóstico.

Abstract OBJECTIVE: To determine the genetic mutations in hereditary pattern breast cancer and demonstrate whether there is a significant association between the most common in the Mexican population and the risk of suffering it. MATERIALS AND METHODS: Cross-sectional and observational study conducted at the Hospital Angeles México in coordination with the National Institute of Genomic Medicine. Inclusion criteria: patients with breast cancer and one or more first-degree relatives affected by this disease and patients with ovarian cancer. Exclusion criteria: patients without a history of breast or ovarian cancer, or with a family member in the protocol. The RT2 Profiler plate rearrangement technique was used for Master-Mix Quantinova probe PCR kit. The SPSS version 22 program and Epi Info version 7 were used for the statistical analysis. RESULTS: 39 patients with an average age of 53.2 ± 12.1 years were studied. Progesterone and estrogen receptors showed no difference between groups. There was a greater trend for BRCA1. When studying the mutations with statistical significance, in which the cases of BRCA2 versus without significance and the negative cases stood out, there was no significant statistical difference, but with a tendency to higher frequency of BCRA1. When evaluating breast cancer lines and nuclear grades compared by age, the three nuclear grade groups compared by age showed differences. CONCLUSION: The data obtained show that in the Mexican population the BRCA2 gene has a higher incidence in hereditary cancer, at an age of earlier onset and greater nuclear grade at the time of diagnosis.

Effects of ICI 182, 780, an ERα and ERß antagonist, and G-1, a GPER agonist, on autophagy in breast cancer cells / Efeitos do antagonista seletivo do REα e do REß ICI 182, 780 e do agonista de GPER G-1 no processo de autofagia em células de câncer de mama

ABSTRACT Objective To investigate if ICI 182,780 (fulvestrant), a selective estrogen receptor alpha/beta (ERα/ERβ) antagonist, and G-1, a selective G-protein-coupled receptor (GPER) agonist, can potentially induce autophagy in breast cancer cell lines MCF-7 and SKBr3, and how G-1 affects cell viability. Methods Cell viability in MCF-7 and SKBr3 cells was assessed by the MTT assay. To investigate the autophagy flux, MCF-7 cells were transfected with GFP-LC3, a marker of autophagosomes, and analyzed by real-time fluorescence microscopy. MCF-7 and SKBr3 cells were incubated with acridine orange for staining of acidic vesicular organelles and analyzed by flow cytometry as an indicator of autophagy. Results Regarding cell viability in MCF-7 cells, ICI 182,780 and rapamycin, after 48 hours, led to decreased cell proliferation whereas G-1 did not change viability over the same period. The data showed that neither ICI 182,780 nor G-1 led to increased GFP-LC3 puncta in MCF-7 cells over the 4-hour observation period. The cytometry assay showed that ICI 182,780 led to a higher number of acidic vesicular organelles in MCF-7 cells. G-1, in turn, did not have this effect in any of the cell lines. In contrast, ICI 182,780 and G-1 did not decrease cell viability of SKBr3 cells or induce formation of acidic vesicular organelles, which corresponds to the final step of the autophagy process in this cell line. Conclusion The effect of ICI 182,780 on increasing acidic vesicular organelles in estrogen receptor-positive breast cancer cells appears to be associated with its inhibitory effect on estrogen receptors, and GPER does notseem to be involved. Understanding these mechanisms may guide further investigations of these receptors' involvement in cellular processes of breast cancer resistance.

RESUMO Objetivo Avaliar o efeito dos compostos ICI 182,780 (fulvestranto), um antagonista seletivo dos receptores de estrógeno alfa/beta (REα/REβ), e do G-1, um agonista seletivo de receptores de estrógeno acoplados a proteínas-G (GPER), na possível indução de autofagia em linhagens de câncer de mama MCF-7 e SKBr3, bem como o efeito de G-1 na viabilidade celular. Métodos A viabilidade celular de células MCF-7 e SKBr3 foi avaliada pelo ensaio com MTT. Para investigar a indução da autofagia, células MCF-7 foram transfectadas com GFP-LC3, um marcador de autofagossomos, e analisadas por microscopia de fluorescência em tempo real. As células MCF-7 e SKBr3 foram incubadas com o indicador de compartimentos ácidos laranja de acridina e analisadas por citometria de fluxo como indicativo para autofagia. Resultados Em células MCF-7, o ICI 182,780 e rapamicina após 48 horas levaram à diminuição da viabilidade celular, enquanto o G-1 não alterou a viabilidade no mesmo período de tratamento. Nem o ICI 182,780 e nem o G-1 induziram aumento na pontuação de GFP-LC3 em células MCF-7 até 4 horas. Já os ensaios de citometria de fluxo demonstraram que ICI 182,780 levou ao aumento de compartimentos ácidos em células MCF-7. O G-1 não aumentou estes parâmetros em ambas as linhagens. Por outro lado, ICI 182,780 e G-1 não induziram à redução da viabilidade em células SKBr3 e nem à formação de compartimentos ácidos, como etapa final do processo autofágico. Conclusão O aumento de compartimentos ácidos pelo ICI 182,780 em células de câncer de mama positivas para receptores de estrógeno parece estar associado com seu efeito inibidor de receptores de estrógeno, mas sem o envolvimento de GPER. A compreensão desses mecanismos pode direcionar estudos sobre o envolvimento dos receptores nos processos celulares de resistência do câncer de mama.

Effect of estrogen receptor-α gene polymorphism on serum osteoprotegerin and calcaneus bone density in postmenopausal women in Guangxi Zhuang nationality / 中华老年医学杂志

Objective To investigate the effect of estrogen receptor-α gene polymorphism on osteoprotegerin(OPG)and calcaneus bone density in early and late postmenopausal women in Guangxi Zhuang nationality,in order to provide the theoretical basis for the early prevention and treatment of postmenopausal osteoporosis caused by estrogen receptor gene-induced osteoprotegerin reduction.Methods The broadband ultrasound attenuation in the right heel bone was measured by quantitative ultrasound bone densitometry in 621 postmenopausal women of Guangxi Zhuang nationality.Peripheral blood mononuclear cells and their DNA were extracted.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the estrogen receptor-α gene polymorphism.Serum osteoprotegerin level was determined by enzyme-linked immunosorbent assay.The differences of data distribution of OPG and calcaneus bone density were compared between five items of 3 genotypes and 2 alleles at the same age group of 40-,45-,50-,55-,60-,65-,70-,75-80 years.Results Women aged 60 years and over versus those aged 40-59 years showed that serum osteoprotegerin (OPG) and bone mineral density (BMD) were decreased (P ＜ 0.05),and had no significant difference among allele P,p,genotype Pp,pp,PP of ER-α Puv-Ⅱ polymorphism at the same age groups(P＞0.05).Women aged 60 years and over showed that ER-α Puv Ⅱ polymorphism of allele big P versus p,Pp,pp,PP in the same age groups had significantly decreased serum osteoprotegerin and bone mineral density.Women aged 65 years and over showed that ER-α Xba Ⅰ polymorphism of heterozygote Xx versus xx,XX,X,x in the same age groups had a significantly increased serum osteoprotegerin and bone mineral density(P＜0.05).Conclusions Women with big P allele of ER-a Pvu Ⅱ polymorphism have low serum osteoprotegerin level and a decreased bone mineral density,who are prone to postmenopausal osteoporosis.Thus,P allele of ER-α Pvu Ⅱ polymorphism is a causative agent.More attention should be paid to early prevention and treatment.But,women with the Xx heterozygote of ER-α Xba Ⅰ polymorphism have high serum osteoprotegerin level and an increased bone mineral density,who are not easy to suffer from postmenopausal osteoporosis.Therefore,Xx heterozygote of ER-α Xba Ⅰ polymorphism is a protective agent.The prevention and treatment of postmenopausal osteoporosis should be individualized based on estrogen receptor-α gene polymorphism.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor ( ER) and progesterone receptor ( PR).Methods We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins ,ER and PR in tissues were determined by immunohistochemistry.Results The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues (13.3%) ( χ2 ＝145.067,P＜0.05).The positive expression rates of ER and PR in the endometrial carcinoma tissues (60.0%,56.7%) were lower than those in the normal endometrial tissues (100.0%,100.0%) (χ2 ＝93.490,96.698,all P＜0.05).The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues ( r＝－0.472,－0.513,all P＜0.05).The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage , depth of myometrial invasion and lymph node metastasis of endometrial carcinoma (83.1% vs.93.0%,82.6% vs. 98.0%,97.6% vs.84.6%;81.7% vs.29.2%,91.3% vs.17.6%,19.5% vs.82.1%) ( χ2 ＝6.628,7.228, 4.779;33.062,66.292,43.984,all P＜0.05),and were not associated with age ,degree of differentiation and tumor diameter (all P＞0.05).The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma (78.9% vs.24.5%,84.1% vs.20.0%,χ2 ＝34.919,48.577,all P＜0.05),and were not associated with age ,degree of differentiation,tumor diameter and lymph node metastasis (all P＞0.05).Conclusion The development of endometrial cancer is related to the overexpression of cluster proteins,and the expression of cluster proteins may be regulated by estrogen and progesterone .

Research progress of CDK4/6 inhibitors in ER-positive and HER2-negative advanced breast cancer / 国际外科学杂志

Endocrine therapy is one of the standard treatment options for breast cancer which plays an important role in treating patients with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer.However,some patients develop resistance during therapy due to factors such as tumor heterogeneity,which is particularly acute in the treatment of advanced breast cancer.Based on aiming at a rational and effective treatment,some clinical trials recently have demonstrated that compared to endocrine therapy alone,cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy can significantly improve the prognosis of ER-positive,HER2-negative advanced breast cancer.Its main products are Palbociclib,Ribociclib and Abemaciclib.This review mainly focuses on the mechanism and related clinical trials of CDK4/6 inhibitor inhibitors in ER-positive,HER2-negative advanced breast cancer.

Application of CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer / 国际肿瘤学杂志

With roles of blocking cell proliferation, cyclin-dependent protein kinase (CDK) 4/6 inhi-bitors are effective and safe complementary therapies for hormone receptor-positive breast cancer. CDK4/6 inhibitors combined with endocrine therapy significantly improve the prognosis of patients with advanced or metastatic breast cancer, especially those with endocrine resistance. Indications for CDK4/6 inhibitors are also expected to broaden into early-stage breast cancer. However, mechanisms of resistance of CDK4/6 inhibitors remain elusive.

Expression of cluster proteins in endometrial carcinoma and its relationship with ER and PR / 中国基层医药

Objective@#To investigate the expression of cluster proteins in endometrial cancer tissues and its correlation with estrogen receptor (ER) and progesterone receptor (PR).@*Methods@#We selected 120 cases of endometrial cancer tissue specimens and 120 cases of normal endometrial tissue specimens from January 2013 to December 2017 in the Maternal and Child Health Hospital of Huzhou.The expression of cluster proteins, ER and PR in tissues were determined by immunohistochemistry.@*Results@#The positive rate of cluster proteins in the endometrial carcinoma tissues(89.2%) was higher than that in the normal endometrial tissues(13.3%) (χ2=145.067, P<0.05). The positive expression rates of ER and PR in the endometrial carcinoma tissues(60.0%, 56.7%) were lower than those in the normal endometrial tissues(100.0%, 100.0%) (χ2=93.490, 96.698, all P<0.05). The cluster proteins was negatively correlated with ER and PR in the endometrial carcinoma tissues (r=-0.472, -0.513, all P<0.05). The expression of cluster protein and ER in the endometrial carcinoma were associated with FIGO stage, depth of myometrial invasion and lymph node metastasis of endometrial carcinoma(83.1% vs.93.0%, 82.6% vs.98.0%, 97.6% vs.84.6%; 81.7% vs.29.2%, 91.3% vs.17.6%, 19.5% vs.82.1%) (χ2=6.628, 7.228, 4.779; 33.062, 66.292, 43.984, all P<0.05), and were not associated with age, degree of differentiation and tumor diameter (all P>0.05). The positive expression of PR in the endometrial carcinoma was correlated with the FIGO stage and depth of myometrial invasion of the endometrial carcinoma(78.9% vs.24.5%, 84.1% vs.20.0%, χ2=34.919, 48.577, all P<0.05), and were not associated with age, degree of differentiation, tumor diameter and lymph node metastasis (all P>0.05).@*Conclusion@#The development of endometrial cancer is related to the overexpression of cluster proteins, and the expression of cluster proteins may be regulated by estrogen and progesterone.

Ultrasonographic features of calcified and non-calcified ductal carcinoma in situ of breast and their expression of estrogen receptor and human epidermal growth factor receptor-2 / 中国医学影像技术

Objective: To compare the ultrasonographic features of calcified and non-calcified ductal carcinoma in situ (DCIS) of breast, and to explore the difference of the expression of estrogen receptor (ER) and human epidermal growth factor receptor-2 (Her-2). Methods A total of 148 patients with pathologically confirmed DCIS were retrospectively analyzed and divided into calcified DCIS group (n=66) and non-calcified DCIS group (n=82) according to the presence of microcalcification in ultrasonography. The differences of the ultrasonographic features, ER and Her-2 positive expression were analyzed. Results The signs of mass, ductal ectasia and elastographic scores showed statistically significant differences between the 2 groups (all P0.05). ER positive rate was 42.42% (28/66) in calcified DCIS group and 69.51% (57/82) in non-calcified DCIS group. The difference of ER positive rate between the two groups was statistically significant (P<0.01). Her-2 positive in calcified DCIS group was 30.30% (20/66), while in the non-calcified DCIS group was 14.63% (12/82; P=0.02). Conclusion The ultrasonographic features are different between calcified breast DCIS and non-calcified DCIS. Positive ER is more common in non-calcified DCIS, while high Her-2 expression is more common in calcified DCIS, indicating that calcified DCIS may have rather aggressive histological features.

Application of CDK4 / 6 inhibitors in the treatment of hormone receptor-positive breast cancer / 国际肿瘤学杂志

With roles of blocking cell proliferation,cyclin-dependent protein kinase (CDK)4 / 6 inhi-bitors are effective and safe complementary therapies for hormone receptor-positive breast cancer. CDK4 / 6 inhibitors combined with endocrine therapy significantly improve the prognosis of patients with advanced or metastatic breast cancer,especially those with endocrine resistance. Indications for CDK4 / 6 inhibitors are also expected to broaden into early-stage breast cancer. However,mechanisms of resistance of CDK4 / 6 inhibitors remain elusive.