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.

Cáncer de mama metastásico y embarazo: reporte de caso / Metastatic breast cancer and pregnancy: a case report

Resumen ANTECEDENTES: El cáncer de mama es la segunda neoplasia maligna más común asociada con el embarazo. Su tratamiento es complejo debido a los riesgos en el feto en el contexto del tratamiento de la madre. CASO CLÍNICO: Paciente de 28 años, enviada del Hospital Naval de Chetumal, Quintana Roo, con 13.1 semanas de embarazo por fecha de la última menstruación. En la tomografía computada se advirtió la existencia de un derrame pleural del 70%, otro pericárdico y sospecha de metástasis osteoblástica a la columna torácica. En la exploración física se encontró con dinámica ventilatoria, amplexión y amplexación disminuida derecha, hipoventilación interescapular y basal derecha, con disminución a la trasmisión de voz, submatidez basal derecha y, hacia el lado izquierdo, un murmullo vesicular. Los estudios citoquímico y citológico de líquido pericárdico y pleural se reportaron positivos para malignidad. En la resonancia magnética de la columna se encontraron lesiones sugerentes de actividad tumoral en los cuerpos vertebrales T12 a L5. Debido al avanzado estado metastásico del cáncer se propuso la interrupción del embarazo con el propósito de no retrasar el tratamiento. El perfil biológico reportó: inmunofenotipo triple negativo (receptores de estrógeno y progesterona: negativo, HER2: negativo en células neoplásicas). Se le indicó tratamiento con quimioterapia sistémica (carboplatino-paclitaxel). CONCLUSIÓN: El diagnóstico de cáncer de mama durante el embarazo dificulta la detección e interpretación de las anormalidades mamarias, retrasa el diagnóstico, permite el crecimiento del tumor y se incrementa el riesgo metastásico de la enfermedad. El tratamiento oncológico adecuado y su valoración multidisciplinaria son decisivos para favorecer la supervivencia.

Abstract BACKGROUND: Breast cancer is the second most common malignancy associated with pregnancy. Its treatment is complex due to fetal risks in the context of treatment of the mother. CLINICAL CASE: 28-year-old patient, referred from the Naval Hospital of Chetumal, Quintana Roo, with 13.1 weeks of pregnancy by date of last menstrual period. The CT scan showed a 70% pleural effusion, another pericardial effusion and suspicion of osteoblastic metastasis to the thoracic spine. Physical examination showed ventilatory dynamics, decreased right amplexion and amplexation, interscapular and right basal hypoventilation, with decreased voice transmission, right basal submatitis and, to the left side, a vesicular murmur. Cytochemical and cytological studies of pericardial and pleural fluid were positive for malignancy. MRI of the spine showed lesions suggestive of tumor activity in the vertebral bodies T12 to L5. Due to the advanced metastatic stage of the cancer, termination of pregnancy was proposed in order not to delay treatment. The biological profile reported: triple negative immunophenotype (estrogen and progesterone receptors: negative, HER2: negative in neoplastic cells). Treatment with systemic chemotherapy (carboplatin-paclitaxel) was indicated. CONCLUSION: The diagnosis of breast cancer during pregnancy hinders the detection and interpretation of breast abnormalities, delays diagnosis, allows tumor growth and increases the metastatic risk of the disease. Adequate oncologic treatment and its multidisciplinary assessment are decisive in favoring survival.

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.

Expression and correlation of Fascin-1 and EGFR in hormone receptor-positive breast cancer / 中国医师杂志

Objective To explore the expression and correlation of Fascin-1 and epidermal growth factor receptor (EGFR) in hormone receptor-positive breast cancer.Methods The immunohistochemical technique,EnVision method,was used to evaluate the expression of Fascin-1 and EGFR in 294 cases of hormone receptor-positive breast cancer,which contains 290 cases of estrogen receptor (ER) positive and 244 cases of progestrone receptor (PR) positive.According to ER,PR,Epidermal growth factor receptor 2 (HER2),and Ki-67 status,all cases of hormone receptor-positive breast cancer were categorized into 2 subtypes:160 cases of luminal A and 134 cases of luminal B.Results Fascin-1 and EGFR protein positive rates in hormone receptor-positive breast cancer was 13.9％ (41/294) and 30.6％ (90/294),respectively.Fascin-1 positive rate was significantly higher in EGFR positive cases (30.0％,27/90) than in EGFR negative cases (6.9％,14/204) (x2 =27.857,P =0.000).In the ER positive and PR positive cases,Fascin-1 positive rates were both significantly higher in EGFR positive cases than in EGFR negative cases (x2 =29.23,P =0.000;x2 =27.596,P =0.000,respectively).In the Luminal A and Luminal B subtype,Fascin-1 positive rates were also both significantly higher in EGFR positive cases than in EGFR negative cases (x2 =23.247,P=0.000;x2 =5.325,P=0.021,respectively).Conclusions EGFR signal pathway may positive regulate Fascin-1 expression in hormone receptor-positive breast cancer.

Mammographic density among indigenous women in forested areas in the state of Amapá, Brazil: a cross-sectional study / Densidade mamográfica em mulheres indígenas de áreas da floresta do estado do Amapá, Brasil: estudo transversal

ABSTRACT CONTEXT AND OBJECTIVE: There is no register of breast cancer cases among indigenous populations in Brazil. The objective here was to evaluate the association of clinical and demographic characteristics with mammographic density among indigenous women. DESIGN AND SETTING: Cross-sectional analytical study conducted in indigenous territories in the state of Amapá, Brazil. METHODS: Women were recruited from three indigenous territories and underwent bilateral mammography and blood collection for hormonal analysis. They were interviewed with the aid of an interpreter. Mammographic density was calculated using computer assistance, and was expressed as dense or non-dense. RESULTS: A total of 137 indigenous women were included in this study, with an average age of 50.4 years, and an average age at the menarche of 12.8 years. Half (50.3%) of the 137 participants had not reached the menopause at the time of this study. The women had had an average of 8.7 children, and only two had never breastfed. The average body mass index of the population as a whole was 25.1 kg/m2. The mammographic evaluation showed that 82% of women had non-dense breasts. The clinical characteristics associated with mammographic density were age (P = 0.0001), follicle-stimulating hormone (FSH) (P < 0.001) and estrogen levels (P < 0.01). CONCLUSIONS: The majority of the indigenous women had non-dense breasts. Age, menopausal status and FSH and estrogen levels were associated with mammographic density.

RESUMO CONTEXTO E OBJETIVO: Não há registro de casos de câncer de mama em populações indígenas no Brasil. O objetivo foi avaliar a associação de características clínicas e demográficas com a densidade mamográfica em mulheres indígenas. TIPO DE ESTUDO E LOCAL: Estudo transversal, analítico, realizado em territórios indígenas no estado do Amapá, Brasil. MÉTODOS: Mulheres foram recrutadas de três territórios indígenas e submetidas a mamografia bilateral e a coleta de sangue para análise hormonal. As participantes foram entrevistadas com a ajuda de um intérprete. A densidade mamográfica foi calculada com assistência de computador, e expressa como densa ou não densa. RESULTADOS: 137 mulheres foram incluídas no estudo, com média de 50,4 anos e média de idade à menarca de 12,8 anos. Metade (50,3%) das 137 participantes não havia entrado na menopausa no momento do estudo. As mulheres tinham em média 8,7 filhos, e duas nunca haviam amamentado. O índice de massa corpórea médio da população como um todo foi de 25,1 kg/m2. A análise mamográfica mostrou que 82% das mulheres tinham mamas não densas. As características clínicas associadas com a densidade mamográfica foram idade (P = 0.0001), hormônio folículo-estimulante (FSH, P < 0,001) e níveis de estrogênio (P < 0,01). CONCLUSÕES: A maioria das indígenas tinha mamas não densas. Idade, status menopausal e níveis de estrógeno e FSH foram associados com a densidade mamográfica.

Relationships of ductal carcinoma in situ calcification feature and ER, PR and HER2 expression / 国际肿瘤学杂志

Objective To discuss the relationships of ductal carcinoma in situ calcification feature and estrogen receptor (ER),progesterone receptor (PR),human epidermal growth factor receptor 2 (HER2) expression.Methods The mammary gland molybdenum target X-ray results of 226 patients with ductal carcinoma in situ were retrospectively analyzed in our hospital during January 2013 to December 2016.All patients were divided into calcification group (n =110) and no calcium group (n =116).Immunohistochemical method was used to detect the expressions of ER,PR and HER2,and their relationships with calcification feature were analyzed.Results The positive expression rates of ER and PR in calcification group were 72.73％ and 54.55％ significantly higher than those in no calcium group (39.66％ and 38.79％;x2=25.033,P ＜0.001;x2 =5.632,P =0.036).The positive expression rate of HER2 in calcification group was 45.45％,significantly lower than that of the no calcium group (82.76％,x2 =34.358,P ＜ 0.001).According to the single factor analysis,the calcified form (x2 =31.098,P ＜ 0.001;x2 =24.117,P =0.003),distribution (x2=30.272 P＜0.001;x2=11.811,P=0.008),number (x2 =15.533 P＜0.001;x2 =7.875,P=0.019) and concomitant situation (x2 =27.915,P ＜0.001;x2 =7.229,P =0.027) were associated with ER and PR expressions,and the calcified distribution (x2 =8.068,P =0.035),number (x2 =60.768,P ＜0.001) and concomitant situation (x2 =24.915,P ＜ 0.001) were associated with HER2 expression.Logistic regression analysis shows that the small polymorphic form,cluster distribution,number ＞ 30,with mass were the independent prediction factors of ER,PR and HER2 expressions (all P ＜ 0.001).Conclusion The mammary gland molybdenum target calcification features of ductal carcinoma in situ are associated with ER,PR and HER2 expressions,the small polymorphic form,cluster distribution,number ＞ 30,with mass can be used as important reference indexes to preliminarily predict biological therapy and expressions of prognostic factors.

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients

BACKGROUND: Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS: To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS: PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS: Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

Expression of ER and PR in the endometrium of patients with intrauterine adhesions / 中华妇产科杂志

Objective To estimate the expression of ER and PR in the endometrium of both intrauterine adhesions (IUA) and non-IUA specimens. Methods The endometrium specimens from patients undergoing hysteroscopy for confirmed moderate IUA (n=20: 10 in proliferative phase, and 10 in secretory phase) were enrolled as the IUA group in Beijing Obstetrics and Gynecology Hospital from October 2014 to August 2015. The specimens scheduled for hysteroscopy due to infertility were recruited into the control group (n=26: 13 in proliferative phase, and 13 in secretory phase). Immunohistochemistry and quantificational real-time PCR (qRT-PCR) were used to detect the expression of ER-α, ER-β and PR in endometrium with different menstrual period in both groups. Results (1) Location: in both groups, the expression of ER-α, ER-β and PR appeared in the endometrial glandular epithelial cells and the stromal cells of the endometrium. The positive brown granules of ER-α, ER-β and PR appeared mainly in cell nucleus. (2) ER-α and ER-β in the endometrium:the protein expression of ER-α and ER-β in IUA group (proliferative phase: 0.657 ± 0.028, 0.493 ± 0.023; secretory phase: 0.537 ± 0.020, 0.365 ± 0.031) were significantly higher than those of control group (proliferative phase: 0.586 ± 0.025, 0.437 ± 0.022; secretory phase:0.459 ± 0.025, 0.323 ± 0.017;all P<0.01). And the ER-αand ER-βmRNA expressions in IUA group were 2.524 ± 0.296, 1.947 ± 0.339, higher than those of control group in the proliferative phase (all P<0.01), and in the secretory phase (1.977±0.333, 1.345±0.292) were also higher than those in the control group (all P<0.01). (3) PR in the endometrium: the protein expression of PR was not significantly different between IUA group (proliferative phase:0.248±0.025, secretory phase:0.194±0.024) and control group (proliferative phase: 0.234 ± 0.019, secretory phase: 0.186 ± 0.020; P=0.162, 0.359). Meanwhile, there were no statistical differences in the mRNA expression of PR in both groups with different menstrual period (proliferative phase: 1.144 ± 0.384 versus 0.981 ± 0.306, secretory phase: 0.763 ± 0.237 versus 0.631 ± 0.203; P=0.270, 0.166). (4) ER and PR expression in menstrual cycles: the expression of ER-α, ER-β and PR in the IUA group changed with the menstrual cycles, and their expression in the proliferative phase were higher than those in the secretory phase (all P<0.05). Conclusions The expression of ER-α and ER-β in the endometrium of IUA patients changes with menstrual cycle, and are higher compared with those in normal endometrium. No difference is found in the PR expression between the two groups.

Study on the changes of gonadotropin releasing hormone agonist in pinopodes / 中华妇产科杂志

Objective To study the changes of gonadotropin releasing hormone agonist (GnRH-a) in pinopodes during luteal phase and to explore the possible mechanism of GnRH-a in luteal phase support of assisted reproductive technology (ART).Methods Totally 40 primary infertility women who were treated with ART due to male factors were enrolled,according to the order of the group they were randomly divided into experimental group and control group.On the 7th day after ovulation,the experimental group received a subcutaneous injection of 0.1 mg of GnRH-a,while the control group received a subcutaneous injection of placebo only (0.9％ salinc 2 ml),3 days later they came to the clinic again.Serum estradiol and progesterone levels were measured before and after treatment in each group.Pinopodes were collected for electron microscopic examination.Levels of ER and PR were detected by western blot.Results (1) There was no significant difference between the experimental group and the control group in the estrogen level before and after the treatment (all P＞0.05).The level of progesterone in the experimental group after treatment [(66.8± 14.9) nmol/L] was significantly higher than that before treatment(P＜0.05);also significantly higher than the same period of the control group (P＜0.05).(2) There was no significant difference in the expression of ER protein in the experimental group before and after treatment (P＞0.05).The expression of PR in the experimental group after treatment was significantly lower than that before treatment (P＜0.05);also lower than the same period of the control group (P＜0.05).(3) Expression amount of pinopodes in the experimental group after treatment was significantly higher than that before treatment [65％ (13/20) versus 25％ (5/20),P＜ 0.05],and the development trend was more mature [the percentage of maturation:75％ (15/20) versus 35％ (7/ 20),P＜0.05].Expression amount of pinopodes after treatment and the percentage of maturation in the experimental group were significantly higher than those in the same period of control group (P＜0.05).Conclusion GnRH-a in luteal phase support may play a role through the corpus luteum,which may promote the secretion of progesterone,downregulation of PR expression,promote the growth of pinopodes,and improve the endometrial receptivity.

Análise dos marcadores imuno-histoquímicos associados com câncer de mama em mulheres na Região das Missões, Rio Grande do Sul, Brasil / Analysis of immunohistochemical markers associated with breast cancer in women in the Region of Missions, Rio Grande do Sul, Brazil

Objetivos: Analisar a distribuição dos subtipos moleculares de câncer de mama e correlacionar esses subtipos com o perfil etário e histológico. Métodos: Trata-se de um estudo observacional, descritivo e retrospectivo. Foram incluídas 110 mulheres com diagnóstico histológico de câncer de mama e análise imuno-histoquímica no período de janeiro de 2013 a dezembro de 2015. Com base nos laudos imuno-histoquímicos, foram definidos quatro subtipos moleculares: luminal A, luminal B, HER-2+ e triplo negativo. Foi realizada análise estatística para correlacionar subtipos moleculares e tipo histológico e idade. Resultados: A idade média das participantes do estudo foi de 56,9 anos (DP=15,15), apresentando pico na faixa etária acima dos 50 anos. O tipo histológico mais frequente (66,4%) foi o carcinoma ductal invasivo (CDI). Quanto à classifica- ção molecular, o luminal B foi o mais frequente, representando 43,6% dos casos. Conclusão: Com base nos marcadores moleculares, os carcinomas da mama foram classificados em quatro subtipos e não apresentaram diferença significativa em relação ao tipo histológico nem à idade.

Objectives: To analyze the molecular subtype's breast cancer distribution and correlate them with age and histological profile. Methods: An observational, descriptive and retrospective study. One hundred and ten women with histological diagnosis of breast cancer and immunohistochemistry analysis, from January 2013 to December 2015, were included. From the reports, four molecular subtypes were defined: luminal A, luminal B, HER-2+ and triple negative. Correlations between molecular subtypes and histologic type and age were evaluated statistically. Results: The average age of the participants of the investigation was 56.9 years (SD=15.15), with a peak in the age group over 50 years. The most common histological type (66.4%) was invasive ductal carcinoma (IDC). The luminal B was the most frequent molecular subtype, representing 43.6% of cases. Conclusions: Based on molecular markers, the breast carcinomas were classified into four subtypes and showed neither significant difference regarding histologic type nor age.

Comparison of Immunohistochemical Indicators between Non-mass-like and Mass-like Breast Cancer / 中国医学影像学杂志

Purpose To explore the expressional differences of immunohistochemical indicators between the non-mass-like and mass-like breast cancers,and to identify the biological characteristics of non-mass-like breast cancer.Material and Methods Various immunohistochemical indicators (HER2,ER,PR,Ki-67) were analyzed in 19 cases non-mass-like cancer and 18 cases mass-like breast cancer retrospectively,and the expressional differences of the two groups were compared.Results 12 cases (63.2％) were diagnosed DCIS in the non-mass-like breast cancer group,but in the mass-like breast cancer group,the majority (12 cases,66.7％) were invasive cancer.HER2,ER,PR expression had no statistical difference between the two types (P＞0.05).But the Ki-67 positive rate expressed in non-mass-like breast cancer was lower significantly (P＜0.05).Conclusion The HE immunohistochemical characteristics of non-mass-like breast cancer are overlapped with that of mass-like breast cancer,but Ki-67 expression has significant difference between the two groups.There are some differences in biological characteristics of these two kinds of breast cancers.

Effect and regulation of metformin on endometrial carcinoma subline of progestin-resistance / 中华妇产科杂志

Objective To investigate the effect and mechanism of metformin on endometrial carcinoma subline of progestin-resistance and find whether metformin could regulate progestin-resistance in endometrial carcinoma. Methods Ishikawa endometrial carcinoma cells were cultured for a long period in the presence of the synthetic medroxyprogesterone 17-acetate (MPA) to generate a subline refractory to the growth-suppressive effects of MPA,named Ishikawa/MPA cells. The effect of MPA (1, 5, 10, 20, 40 and 60 μmol/L) or metformin (1, 10, 20, 40, 60, 70 and 80 mmol/L) on proliferation of the Ishikawa/MPA and parental Ishikawa cells was detected by cell counting kit-8 (CCK-8) method. Western blot was used to detect the effect of metformin and(or)MPA on the expression of PR-B in the Ishikawa/MPA and Ishikawa cells. Results The Ishikawa/MPA showed that growth stimulation rather than inhibition in the Ishikawa cells after low MPA concentration treatment. The doubling time of Ishikawa/MPA cell lines were (43±4) hours and that of Ishikawa cell line were (47 ± 3) hours. No changes in doubling time were observed (t=0.349,P=0.572). Low concentration (1 and 5μmol/L) of MPA could promote the growth of Ishikawa/MPA cells (by 3% and 13%). High concentration (10, 20, 40 and 60 μmol/L) of MPA could inhibited the growth of Ishikawa/MPA cells (by 4%, 3%, 9%and 40%) and the growth of Ishikawa cells (by 41%, 55%, 65%and 66%). At the same concentration, the difference of inhibition rates between the two cell lines were statistically significant (P<0.01). Metformin (1, 10, 20, 40, 60, 70 and 80 mmol/L) could inhibite the growth of Ishikawa/MPA (by-10%, 20%, 56%, 89%, 97%, 98%and 99%) greater than those in parental Ishikawa cells (by-6%, 19%, 37%, 54%, 70%, 72%and 83%), and the inhibitory effect was dose-dependent manner. Western blot assay showed that for Ishikawa cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (53.5±4.0)%and (37.7±5.2)%, which were higher than that in the control group [(23.4 ± 3.0)%], and there were significant the differences (P<0.01). For Ishikawa/MPA cells, the protein expression levels of PR-B in metformin group and MPA+metformin group were respectively (38.6 ± 1.7)%,(36.3 ± 2.5)%,which were higher than those in the control group [(6.4 ± 1.6)%], and there were also significant differences (P<0.01). Conclusion Metformin may regulate the progestin-resistance in endometrial carcinoma by increasing the expression of PR-B.

Suscetibilidade à prematuridade: investigação de fatores comportamentais, genéticos, médicos e sociodemográficos / Preterm birth susceptibility: investigation of behavioral, genetic, medical and sociodemographic factors

Investigar a associação entre fatores de risco genéticos, comportamentais, biológicos e médicos e a ocorrência da prematuridade.

To investigate the association between genetic, behavioral, biological and medical risk factors and the occurrence of preterm birth.

Association of the H770H of PR gene polymorphism with susceptibility to endometriosis / 中华妇产科杂志

Objective To investigate the association of PR gene exon 5 region H770H (rs1042839) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (EM) in southern Han Chinese women. Methods Totally 431 EM patients and 499 non-EM women were collected and separated into EM group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in EM and control groups to evaluate the association of these SNP with the susceptibility to EM by using a fluorescent quantitative PCR-based high resolution melting (HRM) method. Results The C and T of PR H770H allele frequencies among the EM and control groups were 97.9%(844/862), 2.1% (18/862) and 99.4% (992/998), 0.6% (6/998), respectively. The CC, CT and TT of PR H770H genotype frequencies among the EM and control groups were 95.8%(413/431), 4.2%(18/431), 0 and 98.8%(493/499), 1.2%(6/499), 0, respectively. There were statistical significances in the PR H770H alleles and genotypes distributions between the two groups (χ2=7.386, P=0.007;χ2=8.135, P=0.004). Carrying allele C reduced the risk of EM (OR=0.986, 95%CI: 0.976-0.996), while carrying allele T enhanced the risk of EM (OR=3.319, 95%CI: 1.323-8.325); carrying genotype CC reduced the risk of EM 0.970 time (OR=0.970, 95%CI: 0.949-0.991), whereas carrying genotype CT enhanced the risk of EM 3.473 times (OR=3.473, 95%CI:1.391-8.671). Conclusion There is significant association between the polymorphism of PR H770H and genetic susceptibility to EM in southern Han Chinese women.

Perfil epidemiológico dos subtipos moleculares de carcinoma ductal da mama em população de pacientes em Salvador, Bahia / Epidemiological profile of molecular subtypes of breast ductal carcinoma in patients population in Salvador, Bahia

Objetivo: Avaliar o perfil dos subtipos moleculares do câncer de mama em uma população de pacientes de duas clínicas privadas de Salvador, Bahia: o Núcleo da Mama e o Núcleo de Oncologia da Bahia. Metodologia: Estudo de corte transversal que incluiu pacientes do sexo feminino com diagnóstico aná- tomo-patológico de carcinoma invasivo sem tipo especial (ductal invasor). Foram excluídas as pacientes com história de câncer prévio, exceto câncer de pele não melanoma; com dados clínicos anteriores ao tratamento sistêmico indisponíveis e sem laudo de imuno-histoquímica. Foi realizada classificação do câncer de mama com base no subtipo molecular em quatro padrões principais: luminal A, luminal B, HER2+ e triplo-negativo. Frequências e proporções foram estabelecidas para cada um dos subtipos moleculares. Outros dados clínicos e laboratoriais também foram colhidos para estabelecer o perfil da população estudada. Resultados: Foram recrutadas 59 pacientes entre dezembro de 2012 e maio de 2014, com idade média de 56,9 anos. O subtipo molecular mais comum na amostra foi o luminal B, com 35 casos (59,3%), seguido do luminal A, (11 casos; 18,6%), triplo-negativo (6 casos, 10,2%) e HER2+ (7 casos; 11,9%). Conclusões: Corroborando outros estudos realizados em população brasileira, o subtipo luminal B é o mais comum encontrado nesta amostra de pacientes de Salvador, Bahia. O achado ajuda a confirmar o padrão atípico do país em relação ao descrito na literatura internacional, com importantes implicações terapêuticas e prognósticas.

Objective: The aim of this study is to evaluate breast cancer molecular subtype distribution in a female population of two private centers in Salvador, Bahia, Brazil: Núcleo da Mama e o Núcleo de Oncologia da Bahia. Methodology: This is a cross-sectional study involving female patients with pathological diagnosis of invasive ductal carcinoma not otherwise specified (NOS). Patients with history of previous cancer except non-melanoma skin câncer; clinical data prior to systemic treatment unavailable and those without immunohistochemical report were excluded from the study. Breast cancer classification was based on four main molecular subtype patterns: luminal A, luminal B, HER2 + and triple negative. Frequencies and proportions were established for each of the molecular subtypes. Other clinical and laboratory data were also collected to determine baseline characteristics of the population studied. Results: We recruited 59 patients between December 2012 and May 2014 with an average age of 56.9 years. The most common molecular subtype of the sample was luminal B subtype, with 35 cases (59.3%), followed by luminal A (11 cases; 18.6%), triple negative (6 cases, 10.2%) and HER2+ (7 cases; 11.9%). Conclusions: Similar to other studies with Brazilian population samples, luminal B subtype is the most common in this sample of patients in Salvador, Bahia. The finding helps confirm the atypical pattern of the country in relation to that described in international literature, with important therapeutic and prognostic implications.

Comparison of hormonal receptor and HER2 status between ultrasound-guided 14-gauge core needle biopsy and surgery in breast cancer patients

PURPOSE: To evaluate the concordance of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) statuses between ultrasound (US)-guided 14-gauge core needle biopsy (CNB) and surgery and to analyze whether the clinicopathological and imaging features including those from mammography and ultrasonography can predict the concordance in breast cancer patients. METHODS: The concordance of receptor status between CNB and surgery was assessed for 55 breast cancers in 55 women who underwent CNB before treatment. The clinicopathological and imaging features and the concordance rates were compared between the non-neoadjuvant chemotherapy (non-NAC) group and the NAC group according to the initial treatment. The concordance rates were analyzed according to the clinicopathological and imaging features, by using the chi-square or Fisher exact test and McNemar test for the categorical and the independent t-test for continuous variables. RESULTS: Among 55 women, 22 women (40%) were part of the non-NAC group and 33 women (60%) were part of the NAC group. The concordance rates were 0.86-1.00 in the non-NAC group and 0.76-0.88 in the NAC group. In all three receptors, the difference in the concordance rate between the two groups was not significant. In the NAC group, the absence of axillary lymph node metastasis (1.00, P=0.02) and visibility of cancer on mammography (0.93, P=0.04) showed the higher concordance of the HER2 status. CONCLUSION: Concordance of the receptor status between surgery and US-guided 14-gauge CNB was feasible in breast cancer patients. The absence of axillary lymph node metastasis after NAC and the visibility of cancer on mammography prior to NAC may be helpful for predicting the concordance of HER2 in breast cancer patients.

Frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low bone mineral density / Frequência do polimorfismo da interleucina-6, GST, e dos receptores de progesterona em mulheres na pós-menopausa com baixa densidade mineral óssea

CONTEXT AND OBJECTIVE: Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD). Studies have shown that some of the genetic components relating to lower BMD may be detected by polymorphisms. Our aim was to evaluate the frequencies of interleukin-6, GST and progesterone receptor gene polymorphisms in postmenopausal women with low BMD. DESIGN AND SETTING: Cross-sectional study, conducted in a public university in São Paulo, Brazil. METHODS : We evaluated interleukin-6 (IL-6), progesterone receptor gene (PROGINS) and glutathione S-transferase (GST) polymorphisms in 110 postmenopausal women with no previous use of hormone therapy. Tests were performed using DNA-PCR, from oral scrapings. We used Student's t-test and a logistic regression model for statistical analysis. RESULTS : Regarding IL-6 polymorphism, 58.2% of the patients were homozygotes (GG) and 41.8% had allele C (heterozygote or mutant homozygote + GC or CC). PROGINS genotype polymorphism was absent in 79% (wild homozygote or P1/P1) and present in 20.9% (heterozygote or P1/P2). Regarding GSTM1 polymorphism, the allele (1/1) was present in 72.7% of the patients and was absent in 27.3%. We found that IL-6 polymorphism had statistically significant correlations with the L2-L4 T-score (P = 0.032) and with BMD (P = 0.005). Women with IL-6 polymorphism were 2.3 times more likely to have a L2-L4 T-score of less than -1, compared with those not presenting this polymorphism. CONCLUSION: IL-6 gene polymorphism was correlated with low BMD, whereas the PROGINS and GSTM1 polymorphisms did not show any correlation. .

CONTEXTO E OBJETIVO: A osteoporose é uma desordem esquelética caracterizada por baixa densidade mineral óssea. Estudos têm demonstrado que alguns componentes genéticos relacionados com a menor densidade mineral óssea podem ser detectados por polimorfismos. Nosso objetivo foi avaliar a presença do polimorfismo de genes em mulheres pós-menopáusicas com baixa densidade mineral óssea. TIPO DE ESTUDO E LOCAL: Estudo transversal, conduzido em universidade pública em São Paulo, Brasil. MÉTODOS: Avaliamos os polimorfismos relacionados à interleucina-6 (IL-6), o gene receptor de progesterona (PROGINS) e glutationa S-transferase (GST) em 110 mulheres na pós-menopausa sem terapia hormonal prévia. Os testes foram realizados com DNA-PCR a partir de raspados orais. Foram utilizados teste t de Student e modelo de regressão logística para análise estatística. RESULTADOS: Em relação ao polimorfismo IL-6, 58,2% dos pacientes eram homozigotos (GG) e 41,8% tinham o alelo C (heterozigoto ou homozigoto mutante + GC ou CC). Nos genótipos do polimorfismo PROGINS, 79% estavam ausentes (homozigoto selvagem ou P1/P1) e 20,9% presentes (heterozigoto ou P1/P2). No polimorfismo do GSTM1, o alelo (1/1) estava presente em 72,7% dos pacientes e ausente em 27,3%. Encontramos significância estatística entre o polimorfismo genético da IL-6 com o T-score de L2-L4 (P = 0,032) e a densidade mineral óssea (P = 0,005). As mulheres com polimorfismo da IL-6 tiveram 2,3 vezes mais chance de ter menos de -1 na L2-L4 T-score, quando comparadas às não portadoras. CONCLUSÃO: O polimorfismo do gene da IL-6 está correlacionado com baixa densidade mineral óssea, enquanto os polimorfismos GSTM1 e PROGINS não mostraram correlação. .

Changes of estrogen receptor, progesterone receptor and C-erbB-2 expressions in different scheme pre-and post-neoadjuvant chemotherapies for breast cancer / 国际肿瘤学杂志

Neoadjuvant chemotherapy is widely used in the therapy of locally advanced breast cancer.In the recent studies,the expressions of ER,PR and C-erbB-2 in tumor may change in different scheme preand post-neoadjuvant chemotherapies for breast cancer.It is obviously changed in the neoadjuvant chemotherapy scheme of anthracyclines and paclitaxel/docetaxel,but hardly changed in anthracycline-based neoadjuvant chemotherapy scheme.

Avaliação imunoistoquímica dos receptores de estrogênio e progesterona no câncer de mama, pré e pós-quimioterapia neoadjuvante / Immunohistochemical evaluation of estrogen and progesterone receptors of pre and post-neoadjuvant chemotherapy for breast cancer

OBJETIVO: Avaliar a imunoexpressão dos receptores de estrogênio e progesterona em biópsias e peças cirúrgicas de pacientes com câncer de mama pré e pós-quimioterapia neoadjuvante e correlacionar suas alterações com o padrão de resposta à quimioterapia e diagnóstico de menopausa. MÉTODOS: Selecionaram-se 47 pacientes com diagnóstico histopatológico de carcinoma primário de mama localmente avançado. Para cada paciente existiam dois blocos: o espécime da biópsia e o da ressecção cirúrgica. A partir destes blocos foi avaliada a expressão dos receptores hormonais por imunoistoquímica com a técnica da streptoavidina-biotina-imunoperoxidase e anticorpos primários anti-RE e anti-RP. A análise estatística utilizou o teste paramétrico t de Student e o não-paramétrico exato de Fisher, com nível de significância de 5%. RESULTADOS: Das 47 pacientes, 30 apresentavam imunoexpressão positiva dos receptores hormonais. Observou-se redução significativa tanto nos níveis de receptor de estrogênio e progesterona quanto em sua imunoexpressão. Em 53,3% observaram-se mudanças nos níveis expressos de receptor de estrogênio, 56,6% em receptor de progesterona, 26,6% na imunoexpressão do receptor de estrogênio e 33,3% na imunoexpressão do receptor de progesterona. Não foi encontrada significância estatística ao correlacionar-se a influência da resposta à quimioterapia e do diagnóstico de menopausa nas pacientes com a variação na expressão dos receptores hormonais. CONCLUSÃO: A quimioterapia neoadjuvante alterou significativamente a imunoexpressão dos receptores hormonais nas pacientes da amostra, reduzindo sua positividade nas células tumorais.

OBJECTIVE: To evaluate the immunoexpression of estrogen and progesterone receptors in biopsies and surgical specimens of patients with breast cancer before and after neoadjuvant chemotherapy and to correlate their changes with the pattern of response to chemotherapy and diagnosis of menopause. METHODS: We selected 47 patients with histological diagnosis of locally advanced primary breast carcinoma. For each patient there were two blocks: the biopsy specimen and surgical resection one. From these blocks hormone receptor expression was assessed by immunohistochemistry using the technique of streptoavidin-biotin-immunoperoxidase and anti-ER and anti-PR primary antibodies. The statistical analysis used the Student's t test and the nonparametric Fisher's exact test, with significance level of 5%. RESULTS: Of the 47 patients, 30 showed positive immunostaining for hormone receptors. There was significant reduction in the levels of both estrogen and progesterone receptors and in their immunoreactivity. In 53.3% we observed changes in levels of estrogen receptor expression, 56.6% in the progesterone receptor, 26.6% in the immunoexpression of estrogen receptor immunoreactivity and 33.3% in the immunoreactivity of the progesterone receptor. There was no statistical correlation between the influence of the response to chemotherapy and the diagnosis of menopause in women with variation in the expression of hormone receptors. CONCLUSION: Neoadjuvant chemotherapy has significantly altered hormone receptor immunoreactivity in patients in the sample, reducing its positivity in tumor cells.