Dysregulation of serum miR-1204 and its potential as a biomarker for the diagnosis and prognosis of breast cancer

SUMMARY OBJECTIVE A previous study has reported that miR-1204 exerted oncogenic effects in breast cancer (BC). The purpose of our paper was to evaluate the expressions of tissue and serum miR-1204 in patients with BC and further investigate its biomarker potential. METHODS The expressions of tissue and serum miR-1204 were investigated by qRT-PCR in 144 BC patients and 38 healthy controls. Chi-square tests were conducted to examine the associations between miR-1204 expressions and clinicopathological factors. Then, the associations of miR-1204s level with the survival of BC patients were determined by performing the Kaplan-Meier and multivariate analysis. The receiver operating characteristics (ROC) and area under the OC curve (AUC) were obtained to validate the diagnostic values of miR-1204. RESULTS We found that the expressions of miR-1204 were increased in both tissue and serum samples from BC patients. Multivariate assays identified tissue and serum miR-1204 overexpression as an independent poor prognostic factor. In addition, ROC curve assays indicated that tissue and serum miR-1204 are potential diagnostic markers of BC. CONCLUSIONS Detection of tissue and serum miR-1204 levels could have clinical potential as a novel prognostic/diagnostic biomarker for BC patients.

RESUMO OBJETIVO Um estudo anterior indicou que o miR-1204 exerce efeitos oncogênicos no Câncer de Mama (CM). O objetivo deste trabalho foi avaliar as expressões de miR-1204 sérico e em tecidos em pacientes com CM e investigar o seu potencial biomarcador. METODOLOGIA As expressões de miR-1204 sérico e em tecidos foram investigadas por qRT-PCR em 144 pacientes com CM e 38 controles saudáveis. Testes qui-quadrados foram realizados para examinar as associações entre as expressões de miR-1204 e os fatores clinicopatológicos. Em seguida, as associações entre nível de miR-1204s e sobrevida de pacientes de CM foram determinadas através de análises de Kaplan-Meier e multivariadas. A Curva Característica de Operação do Receptor (ROC) e área sob a curva (AUC) foram obtidas para validar o valor diagnóstico do MIR-1204. RESULTADOS Descobrimos que as expressões do MIR-1204 estavam aumentadas em amostras de tecido e séricas de pacientes com CM. Análises multivariadas identificaram a superexpressão de miR-1204 sérico e em tecidos como um fator independente de prognóstico ruim. Além disso, as curvas ROC indicaram que o miR-1204 sérico e em tecidos é um possível marcador de diagnóstico de CM. CONCLUSÃO A detecção dos níveis MIR-1204 em tecidos e séricos pode ter potencial clínico como um novo biomarcador de prognóstico/diagnóstico para pacientes de CM.

Comparison of serum NEDD-9, CA 15-3, and CEA levels and PET metabolic parameters in breast cancer patients with 18 F-FDG PET / CT

SUMMARY OBJECTIVE Analyze the over expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) deregulated associated with a poor prognosis in various carcinomas. Our objective was to investigate the relationship between the levels of NEDD-9, CA 15-3, and CEA and PET (SUVmax, MTV40, TLG40) with the clinical parameters of patients with breast cancer (BC). METHODS One hundred and eleven patients (82 BC patients who underwent 18F-FDG PET/CT and 29 healthy controls) were evaluated. SUVmax, MTV, and TLG of the primary tumor were compared with the molecular and histopathological subtypes. 18F-FDG, MTV, and TLG were evaluated based on the clinical data, i.e., nodal involvement, distant metastasis, ER and PR status, Ki-67, serum levels of NEDD-9, CA15-3, and CEA. We compared the NEDD-9 in the BC and healthy control groups. RESULTS The mean ± SD of SUVmax in the 82 patients was 13.0 ± 8.6. A statistically significant relationship (p = 0.022) was found between the molecular subtypes and 18F-FDG uptake. The relationship between 18F-FDG uptake and TLG measured in patients <50 years, ER-PR negativity, and HER2 positivity were statistically significant (p=0.015, 0.007, 0.046, and 0.001, respectively). MTV40, TLG40, and CA 15-3 in metastatic patients were statistically significant (p=0.004, 0.005, and 0.003, respectively). NEDD-9 in the BC group was significantly higher than in the healthy group (p=0.017). There was a positive correlation between SUVmax and Ki67 and CA 15-3; MTV40 and CEA; CA 15-3, CEA, SUVmax, and MTV40; a negative correlation was found between CEA, TLG40, and age. CONCLUSION The use of SUVmax, MTV40, and TLG40 parameters with NEDD-9 and tumor markers has been shown to provide a high diagnostic, predictive, and prognostic value for the management of BC. This is considered to be the basis of interventions focused on the treatment objectives related to NEDD-9.

RESUMO OBJETIVO Analisar a associação da superrexpressão das células NEDD-9 ao prognóstico negativo em vários tipos de carcinoma. Nosso objetivo foi investigar a relação entre os níveis de NEDD-9, CA 15-3 e CEA e PET (SUVmax, MTV40, TLG) e os parâmetros clínicos em pacientes com câncer de mama (CM). MÉTODOS Cento e onze pacientes (82 pacientes de CM submetidos a 18F-FDG PET/TC e 29 controles saudáveis) foram avaliados. SUVmax, MTV, e TLG do tumor primário foram comparados nos subtipos molecular e histopatológico. A captação de 18F-FDG, MTV, e TLG foi avaliada com base em dados clínicos (envolvimento nodal, metástase distante, status de ER e PR, Ki-67, níveis séricos de NEDD-9, CA15-3 e CEA). Foi comparada a NEDD-9 do grupo de CM e o controle saudável. RESULTADOS A média ± DP de SUVmax de 82 pacientes foi de 13,0 ± 8,6. Uma relação estatisticamente significativa (p=0,022) foi encontrada entre subtipos moleculares e captação de 18F-FDG. A relação entre captação de 18F-FDG e TLG medida em pacientes com idade <50 anos, ER-PR negativo e HER2 positivo foi estatisticamente significativa (p=0,015; 0,007; 0,046; e 0,001, respectivamente). MTV40, TLG40 e CA 15-3 em pacientes metastáticos foram estatisticamente significantes (p=0,004, 0,005 e 0,003, respectivamente). NEDD-9 no grupo BC foi significativamente maior do que no grupo saudável (p=0,017). Uma correlação positiva foi encontrada entre SUVmax e Ki67 e CA 15-3; MTV40 e CEA; CA 15-3, CEA, SUVmax e MTV40; uma correlação negativa foi encontrada entre CEA, TLG40 e idade. CONCLUSÃO O uso dos parâmetros SUVmax, MTV40 e TLG40 com NEDD-9 e marcadores tumorais demonstrou um alto valor diagnóstico, preditivo e prognóstico para o manejo do CM. Isso é considerado a base para intervenções focadas nos objetivos de tratamento relacionados às NEDD9.

Gynecological cancer and metabolic screening of 1001 elderly Brazilian women

SUMMARY OBJECTIVE The aim of this study was to evaluate gynecological cancer and metabolic screening of Brazilian women aged 65 years or older. METHODS This retrospective descriptive study was conducted by including 1,001 Brazilian patients of the gynecological geriatric outpatient office of our institution to evaluate the influence of age on gynecological cancer and metabolic screening parameters at the first clinical visit. All patients were divided into three groups: a) 65 to 69 years; b) 70 to 74 years; c) ≥ 75 years. We considered clinical, laboratorial, and image data as variables of this study. The Chi-square test was used to assess the proportion of differences among the age groups, and Kruskal-Wallis was used for quantitative variables. RESULTS The values of BMI and height in the group over 75 years was lower than that of the 65 to 69 years (p = 0.001). Regardless of the age group, high arterial blood pressure levels were found in 85.45% of participants. Also, many patients had glucose intolerance in the blood. The pelvic ultrasonography showed abnormal endometrial echo thickness (> 5 mm) in 6.14% of patients, but with no significant statistical difference between the age groups. A total of 4.04% of patients had ovaries with high volume values ( > 6.1 mL). Abnormal mammography (BI-RADS 3 or 4) was observed in 12.21%. CONCLUSIONS our data suggest that a great reduction in BMI and stature is more frequent in the group over 75 years. Also, systemic arterial hypertension and carbohydrate disturbance are frequent morbidities in women over 65 years.

RESUMO OBJETIVO O objetivo deste trabalho foi estudar retrospectivamente alguns dados clínicos, laboratoriais e imagens de um grupo de idosas brasileiras. MÉTODOS Estudo observacional retrospectivo realizado com inclusão de 1.001 mulheres brasileiras atendidas no ambulatório de geriatria ginecológica de nossa instituição. Foram analisados: a idade dos pacientes na primeira consulta clínica e a idade na menopausa natural; alguns achados clínicos durante um exame ginecológico; resultados de análises laboratoriais. Considerou-se a relação dessas variáveis com o grupo da idade das mulheres. O teste do qui-quadrado foi utilizado para avaliar os dados e para algumas variáveis, Kruskal-Wallis ou Anova. RESULTADOS A avaliação do IMC e da estatura nas diferentes faixas etárias das mulheres mostrou que, com o aumento da idade, há diminuição do IMC e da estatura (p=0,001). Nível anormal de pressão arterial estava presente em 85,45%. De acordo com o grupo de idade, as medidas laboratoriais foram avaliadas pelo método estatístico Kruskal-Wallis, e a Anova mostrou diferença estatisticamente significante apenas no valor da creatinina, com pequeno aumento com a idade. A ultrassonografia pélvica foi alterada com espessura endometrial normal (>5 mm) em 29 (6,14%), mas sem diferença estatística significativa com os grupos de idade, e os ovários mostraram sete (4,04%) com volume anormal (>6,1). Mamografia anormal (BI-Rads 3 ou 4) foi observada em 104 pacientes (12,21%). CONCLUSÕES O estudo conclui que, com o aumento da idade, há redução do IMC e da estatura. A hipertensão é morbidade frequente. Os dados laboratoriais e a avaliação de imagens deste estudo são importantes para aumentar o conjunto de informações sobre mulheres idosas e talvez para melhorar a assistência à saúde.

Changes in Cardiac Autonomic Modulation in Women with Breast Cancer Using Aromatase Inhibitors and the Relation with Biochemical Variables / Alterações na Modulação Autonômica Cardíaca em Mulheres com Câncer de Mama em Uso de Inibidores de Aromatase e sua Relação com Variáveis Bioquímicas

Abstract Background: The use of autonomic modulation as a predictor of cardiovascular risk in women with breast cancer is important. Objective: To evaluate the cardiac autonomic modulation of postmenopausal women using aromatase inhibitors for breast cancer treatment, as well as its relation with the following biochemical variables. Methods: Postmenopausal women who did not have breast cancer (n = 33) and postmenopausal women with breast cancer (n = 15). For evaluation of the autonomic modulation the heart rate was recorded beat-to-beat for 30 minutes and the series of RR intervals obtained were used to calculate the following heart rate variability indices: Mean RR ms, SDNN (standard deviation of all normal RR intervals, expressed in milliseconds) ms, Mean HR, RMSSD (square root of the mean of the squared differences between adjacent normal RR interval) ms, NN50 (number of pairs of successive NNs that differ by more than 50 ms) count, pNN50% (proportion of NN50 divided by total number of NNs), RRtri (RR triangular), TINN (triangular interpolation of NN interval) ms, SD1 ms, SD2 ms, LF ms2, HF ms2, LH/HF ms2. The values of biochemical variables (fasting glycemia, triglycerides, HDL-cholesterol, and C-reactive protein) were analyzed by blood sample. Results: Lower values of heart rate variability indices were observed in postmenopausal women with breast cancer in relation to postmenopausal women who did not have breast cancer: Mean RR (p = 0.03); SDNN (p = 0.03); RMSSD (p = 0.03); NN50 count (p = 0.03); pNN50 % (p = 0.03); RRtri (p = 0.02); SD1 (p = 0.01); SD2 (p = 0.02); LF ms2 (p = 0.01); HF ms2 (p = 0.03).There was an inversely proportional correlation between the indices SDNN, SD2, and HFms2 with triglycerides (SDNN p = 0.04; SD2 p = 0.04; HF ms2 p = 0.04). No statistically significant correlations were found between heart rate variability indices and others variables. Statistical significance was set at 5% for all analyses. Conclusion: Women with breast cancer present reduced autonomic modulation and in these women of heart rate variability indices are inversely correlated with triglyceride values.

Resumo Fundamentos: A modulação autonômica como um preditor de risco cardiovascular em mulheres com câncer de mama é importante. Objetivos: Avaliar a modulação autonômica em mulheres pós-menopausa em uso de inibidores de aromatase como tratamento de câncer de mama, e sua relação com algumas variáveis bioquímicas. Métodos: Foram avaliadas mulheres pós-menopausa sem câncer de mama (n = 33) e mulheres pós-menopausa com câncer de mama (n = 15). Para avaliação da modulação autonômica, a frequência cardíaca (FC) foi registrada batimento a batimento por 30 minutos, e as séries de intervalos RR obtidas foram usadas para o cálculo dos seguintes índices de variabilidade da frequência cardíaca: média de RR ms, SDNN (desvio padrão de todos os intervalos RR normais) ms, FC, RMSSD (raiz quadrada da média das diferenças ao quadrado entre os intervalos RR normais adjacentes) ms, contagem NN50 (número de pares de NNs sucessivos que se diferem em mais de 50 ms), pNN50% (proporção de NN50 dividida pelo número total de NNs), RRtri (RR triangular), TINN (interpolação triangular do intervalo NN) ms, DP1 ms, DP2 ms, LF (baixa frequência) ms2, HF (alta frequência) ms2, LH/HF ms2. Os valores das variáveis bioquímicas (glicemia de jejum, triglicerídeos, HDL-colesterol, e proteína C reativa) foram analisadas das amostras de sangue. O nível de significância adotado nas análises estatísticas foi de 5%. Resultados: As mulheres pós-menopausa com câncer de mama apresentaram menores índices de variabilidade da frequência cardíaca em comparação àquelas sem câncer de mama: média de RR (p = 0,03); SDNN (p = 0,03); RMSSD (p = 0,03); contagem NN50 (p = 0,03); pNN50% (p = 0,03); RRtri (p = 0,02), DP1 (p = 0,01), DP2 (p = 0,02); LF ms2 (p = 0,01); HF ms2 (p = -0,03). Observou-se uma correlação inversamente proporcional dos índices SDNN, DP2 e HF ms2 com triglicerídeos (SDNN p = 0,04, DP2 p = 0,04; HF ms2 0,04). Não houve correlação significativa entre os índices de variabilidade da frequência cardíaca e as demais variáveis. Conclusão: Mulheres com câncer de mama apresentam modulação autonômica diminuída e índices de variabilidade da FC inversamente correlacionados com valores de triglicerídeos.

Repercussions of melatonin on the risk of breast cancer: a systematic review and meta-analysis

SUMMARY Breast Cancer is common in women, but its etiology is not yet fully understood. Several factors may contribute to its genesis, such as genetics, lifestyle, and the environment. Melatonin may be involved in the process of breast cancer. Therefore, the aim of this study is to evaluate the influence of the levels of melatonin on breast cancer through a systematic review and meta-analysis. We performed a systematic review according to PRISMA recommendations. The primary databases MEDLINE, Embase, and Cochrane were consulted. There was no restriction on the year of publication and language. Data of systematic reviews from April 2017 to September to 2017 were analyzed. The meta-analysis was conducted using RevMan 5.3 software provided by the Cochrane Collaboration. From a total of 570 articles, 9 manuscripts were included in this review. They analy onzed women with breast cancer and control patients, of which 10% and 90% were in the reproductive period and after menopause, respectively. The lowest level of melatonin was found in approximately 55% of studies with breast cancer in post-menopause. The metanalyses of the studies demonstrated low levels of melatonin in breast cancer patients (n=963) compared with control patients (n= 1332), with a mean difference between the studies of 8722;3.54 (CI8722;6.01,8722;1.06). Another difference found was in the comparison between smoking patients, with an average difference between 1.80 [0.97-2.63]. Our data suggest that low levels of melatonin might be a risk factor for breast cancer.

RESUMO O câncer de mama é comum em mulheres, mas sua etiologia ainda não é totalmente compreendida. Vários fatores podem contribuir para sua gênese, genética, estilo de vida e meio ambiente. A melatonina pode estar envolvida no processo de câncer de mama. Portanto, o objetivo deste estudo é avaliar a influência dos níveis de melatonina no câncer de mama por meio de uma revisão sistemática e meta-análise. Realizamos uma revisão sistemática de acordo com as recomendações do Prisma. Os principais bancos de dados, Medline, Embase e Cochrane, foram consultados. Não houve restrição quanto ao ano de publicação e idioma. Os dados de revisão sistemática obtidos de abril de 2017 a setembro a 2017 foram analisados. A meta-análise foi conduzida pelo programa RevMan 5.3 fornecido pela Cochrane Collaboration. De um total de 570 artigos, nove foram incluídos nesta revisão. As análises foram conduzidas em mulheres com câncer de mama e pacientes controle, dos quais 10% e 90% estavam no período reprodutivo e após a menopausa, respectivamente. O nível mais baixo de melatonina foi encontrado em aproximadamente 55% dos estudos com câncer de mama na pós-menopausa. As meta-análises de estudos demonstraram os baixos níveis de melatonina em doentes com câncer da mama (n=963), em comparação com os pacientes de controle (n=1.332), sendo a diferença de médias entre os estudos da 8722;3,54 (CI 8722;6,01, 8722;1,06). Outra diferença é demonstrada nas comparações entre pacientes fumantes, sendo a diferença da média entre 1,80 [0,97-2,63]. Nossos dados sugerem que baixos níveis de melatonina podem ser um fator de risco para câncer de mama.

Evaluación del Riesgo, Tamizaje, Diagnóstico Clínico ­ Patológico y Estadificación del Cáncer de Mama: 1er Consenso Nacional del Cáncer de Mama de la Sociedad Panameña de Oncología (SPO) / Risk Assessment, Screening, Clinical ­ Pathological Diagnos is and Staging of Breast Cancer: 1st National Consensus of Breast Cancer of the Panamanian Society of Oncology

El cáncer de Mama es el tumor más frecuente de la mujer y su incidencia va en aumento. En la atención primaria del paciente, se debe establecer el riesgo de padecer cáncer de mama durante la vida, a través de una historia clínica orientada a los factores de riesgo familiares e individuales, de tal forma que podamos implementar las estrategias de tamizaje apropiadas. Las estrategias de ta­mizaje deben ser aplicadas de manera sistemáticas, y los resultados anormales referidos a un cen­tro con experiencia en el diagnóstico. Los pacientes diagnosticados deben ser evaluador por un equipo multidisciplinario con experiencia en el manejo de la muestra, estadificación y tratamiento del cáncer de mama.

Breast cancer is the most frequent tumor in women and its incidence is increasing. In the primary care of the patient, the risk of suffering from breast cancer should be established during life, through a clinical history focused on family and individual risk factors, in such a way that we can implement the appropriate screening strategies. Screening strategies should be applied systematically, and ab­normal results referred to a center with experience in diagnosis . Patients diagnosed should be eva­luated by a multidisciplinary team with experience in the management of the sample, staging and treatment of breast cancer.

Low serum 25-hydroxy vitamin D levels are associated with aggressive breast cancer variants and poor prognostic factors in patients with breast carcinoma

ABSTRACT Objective: This study was conducted to assess the serum 25-hydroxy (OH) vitamin D levels in patients with breast cancer compared to healthy controls and to identify its association with aggressive breast cancer phenotypes. Materials and methods: Serum 25-OH vitamin D levels of 78 breast cancer patients and 78 matched healthy controls were estimated using ELISA. The cases and controls were matched with respect to age, menopausal status, parity, weight, height and co-morbidities. Prognostic factors like grade of tumour, hormone receptor status, HER2 neu status and lymphovascular invasion were compared with 25-OH vitamin D levels. Results: The mean serum 25-OH vitamin D levels of cases were significantly lower compared to the controls (22.33 ± 8.19 vs. 37.41 ± 12.9 ng/mL; p = 0.0001). Patients with higher grades of tumour, non-luminal types of breast cancer and breast cancers with estrogen receptor negativity had significantly lower serum 25-OH vitamin D levels than their opposing groups. Patients with excellent and good Nottingham's prognostic Index (NPI) had significantly higher serum 25-OH vitamin D levels than the moderate and poor NPI groups. Conclusion: Newly diagnosed breast cancer patients have significantly lower serum 25-OH vitamin D levels than healthy controls. Lower level of serum 25-OH vitamin D correlates with aggressive breast cancer phenotypes.

Clinical utility of circulating MicroRNA-21 in breast cancer

Background: Breast cancer remains the most frequent type of cancer in females worldwide, with nearly 1.7 million new cases diagnosed in 2012. In Egypt, breast cancer is the most common malignancy among females accounting for 18.3% of total cancer cases in Egypt. Unfortunately, the traditional imaging techniques as well as the currently accepted markers such as serum CEA and CA 15.3 cannot adequately identify early stage patients. MiRNAs are a class of endogenous non-coding RNAs tilde 22 nucleotides in length, which regulate gene expression primarily at the post-transcriptional level and thus are involved in many cellular processes, such as cell proliferation, differentiation, and apoptosis. One of which is miRNA-21 and its alterations have been shown to play critical roles in breast cancer

Materials and Methods: This is a pilot retrospective case-control study. We quantified serum microRNA-21 expression levels using qRT-PCR in 30 breast cancer patients and another 10 controls in comparison to CA 15-3 as a conventional marker of breast cancer used in clinical practice

Results: MiRNA-21 expression levels in early diagnosis of breast cancer patients with a superior both sensitivity and specificity of 100% specially in comparison with CA 15.3 that displayed 70% sensitivity and 60% specificity

Conclusion: MiRNA-21 levels are significantly higher in breast cancer patients compared to healthy subjects. Furthermore, we found that increased miRNA-21 expression levels correlated with progression of breast cancer stages

Expression of tumor suppressors miR-195 and let-7a as potential biomarkers of invasive breast cancer

OBJECTIVE: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level. Some miRNAs, including let-7a and miR-195, have been described as tumor suppressors. However, the roles of these microRNAs in breast cancer progression remain controversial. The aim of this study is to evaluate miR-195 and let-7a expression as potential biomarkers of invasive breast cancer. METHODS: In the present study, 200 individuals were separated into three groups: (i) 72 women constituting the control group who were selected according to rigorous and well-established criteria; (ii) 56 patients with benign breast tumors; and (iii) 72 patients with malignant breast cancers of different clinical stages. The miR-195 and let-7a expression levels in serum were evaluated by real-time PCR. The results were assessed alone and in combination, and the analysis included an estimation of sensitivity and specificity in ROC curves. RESULTS: Compared with the benign and control groups, both microRNAs were downregulated in the malignant breast cancer patient group. Compared with the malignant group, the combination of both biomarkers in the control and benign groups showed good sensitivity and specificity in the serum with AUCs of 0.75 and 0.72, respectively. The biomarker combination for the control group versus the malignant group exhibited a better sensitivity and specificity than for the benign group versus the malignant group. CONCLUSION: These findings support the evidence that the analysis of miR-195 and let-7a can be used as a non-invasive biomarker for breast cancer detection.

Antral Follicles Count and Anti-Müllerian Hormone Levels after Gonadotoxic Chemotherapy in Patients with Breast Cancer: Cohort Study / Contagem de folículos antrais e níveis de hormônio anti-Mülleriano após quimioterapia gonadotóxica em pacientes com câncer de mama: estudo de coorte

Abstract Aim To assess ovarian reserve (OVR) by means of follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) measurement in eumenorrheic women with breast cancer, exposed to gonadotoxic chemotherapy. Method Fifty-two women (35.3 ± 3.8 years old) with breast cancer and undergoing cyclophosphamide-containing chemotherapy were enrolled. The assessment was performed before chemotherapy (T1) and after 2 (T2) and 6 months (T3). Results Six months after chemotherapy, the prevalence of regular cycles was 60%. Anti-Müllerian hormone decreased down to undetectable levels at T2 and T3 (T1: 2.53 [1.00–5.31]; T2 < 0.08; T3: < 0.08 [< 0.08–1.07] ng/mL), (p< 0.0001). Antral follicle count was 11 [8.0–13.5] follicles at T1 and lower at T2 (5.50 [3.75–8.0] and T3 (5.0 [2.5–7.0]) (p< 0.0001). In patients who remained with regular cycles during chemotherapy or resumed normal menses, FSH and estradiol levels remained unchanged. Conclusion Anti-Müllerian hormone and AFC are useful as markers of OVR decline in women exposed to chemotherapy. Follicle-stimulating hormone is only adequate in women who become amenorrheic.

Resumo Objetivo Avaliar a reserva ovariana (OVR) através da contagem de folículos antrais (AFC), dosagem sérica de hormônio folículo estimulante (FSH) e hormônio anti-Mülleriano (AMH) em mulheres com câncer de mama submetidas a quimioterapia gonadotóxica. Método Foram incluídas na pesquisa 52 mulheres (35,3 ± 3,8 anos) com câncer de mama, em tratamento com quimioterapia com ciclofosfamida. As dosagens e medidas foram realizadas antes do início da quimioterapia (T1) e após 2 (T2) e 6 meses (T3). Resultados Seis meses após quimioterapia, a prevalência de ciclos regulares foi de 60%. O AMH sérico diminuiu a níveis indetectáveis em T2 e T3 (T1: 2,53 [1,00–5,31] ]; T2 < 0,08; T3: < 0,08 [< 0,08–1,07] ng/mL) (p< 0,0001). A contagem de folículos antrais foi de 11 [8,0–13,5] folículos em T1, e ainda menor em T2 (5,50 [3,75–8,0] e T3 (5,0 [2,5–7,0]), (p< 0,0001). Em pacientes que mantiveram ciclos regulares durante a quimioterapia ou retomaram a menstruação normalmente, os níveis de FSH e estradiol permaneceram inalterados. Conclusão O AMH e a AFC são marcadores úteis do declínio da OVR em mulheres expostas à quimioterapia. O FSH só é adequado em mulheres que se tornam amenorreicas.

Is there an association between thyroid function abnormalities and breast cancer?

ABSTRACT Objective The aim of this study was to evaluate the association between thyroid function abnormalities and breast cancer and, in particular, the prognostic markers of breast cancer.. Subjects and methods Baseline levels of thyrotropin, free triiodothyronine, free thyroxine and thyroid autoantibodies were measured in 97 women with primary breast cancer, 27 women with benign breast disease, and 4 women with atypical ductal hyperplasia. Their baseline levels were compared with those in 48 healthy women with a normal mammography in the last 2 years. Results There were no significant associations between history of thyroid disease and breast cancer (p = 0.33). The mean baseline levels of triiodothyronine and thyrotropin did not differ significantly between the compared groups. The mean baseline levels of free thyroxine were found to be significantly higher in the breast cancer group, even after adjusting for thyroid replacement therapy. The presence of thyroid antibodies did not differ significantly between the compared groups. In a subgroup analysis, breast cancer cases with thyroid disease and particularly hypothyroidism had a significantly lower incidence of lymph node metastases compared with breast cancer cases without thyroid disease. Conclusions Our data confirmed the proliferative effect of thyroid hormones on breast cells, which had previously been shown in vitro. Additionally, thyroid disease and particularly hypothyroid function appeared to be associated with a lower incidence of lymph node metastases. Further studies to determine the prognostic role of thyroid hormones in breast cancer are warranted.

Estrone and Estradiol Levels in Breast Cancer Patients Using Anastrozole Are Not Related to Body Mass Index / Níveis de estrona e estradiol em pacientes com câncer de mama usando anastrozol não estão relacionados ao índice de massa corpórea

ABSTRACT Objective: Obesity is associated with an increased risk for breast cancer. Recent studies have shown that aromatase inhibitors may be less effective in women with a high body mass index (BMI). The aim of this study was to establish the relationship between the BMI and plasma estrone and estradiol levels in postmenopausal women with hormone receptor-positive breast cancer using anastrozole. Methods: In this cohort study, the patients were divided into three groups according to BMI (normal weight, overweight and obese) to compare and correlate plasma hormone levels before starting anastrozole hormone therapy and three months after treatment. Plasma hormone levels were compared for age and use of chemotherapy. Results: A statistically significant reduction in estrone and estradiol levels was observed between baseline and three months after starting the anastrozole treatment (p < 0.05). There was no statistically significant difference in plasma estrone and estradiol levels among the BMI groups (p > 0.05), but a significant reduction in plasma estrone levels was observed after three-months' treatment relative to baseline in all groups, as well as a reduction in estradiol in the obese group (p < 0.05). The use of chemotherapy and age > 65 years had no influence on plasma steroid levels. Conclusion: Changes in estrone and estradiol levels in the studied groups were not associated with BMI, chemotherapy or age.

RESUMO Objetivo: A obesidade está associada com risco aumentado de câncer de mama. Estudos recentes têm mostrado que os inibidores de aromatase podem ser menos eficazes em mulheres com alto índice de massa corporal (IMC). O objetivo deste estudo foi estabelecer a relação entre o IMC e os níveis plasmáticos de estrona e estradiol em mulheres no período pós-menopausa com câncer de mama receptor hormonal positivo, em tratamento com anastrozol. Métodos: Este estudo de coorte acompanhou três grupos de pacientes de acordo com o seu IMC (peso normal, sobrepeso e obesidade), a fim de comparar e correlacionar as dosagens dos hormônios estrona e estradiol antes e após três meses do uso do anastrozol. Os níveis plasmáticos dos hormônios foram também relacionados à idade do paciente e ao uso da quimioterapia. Resultados: Redução estatisticamente significativa de estrona e estradiol foi observada entre os níveis basais e três meses após o início do tratamento com anastrozol (p < 0,05). Não houve diferença estatisticamente significativa entre os níveis plasmáticos de estrona e estradiol em relação ao IMC (p > 0,05), mas houve redução significativa entre os níveis plasmáticos basais de estrona após o tratamento em todos os grupos, e redução de estradiol no grupo de pacientes obesas (p < 0,05). A condução da quimioterapia e da idade acima de 65 anos não interfere com os níveis plasmáticos de esteroides. Conclusão: Os níveis plasmáticos de estrona e estradiol nos grupos estudados não foram alterados em termos de IMC, quimioterapia e idade.

Detection of Circulating Tumor Cells in Breast Cancer Patients Using Cytokeratin-19 Real-Time RT-PCR

PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.

Granzyme H serum levels variations with both reproductive hormone receptors, and related hormone receptors in breast cancer patients

Breast Cancer [BC] is the most common cancer in Iranian women, meanwhile the Iranian patients are relatively young. Granzyme H [GZMH] is a functional cytotoxic serine protease of NK cell granules, which expands the cell death-inducing repertoire of innate immune system. GZMH is constitutively and highly expressed in human NK cells, in order to possess chymotrypsin-like [chymase] enzymatic activity. The purpose of this study was to determine GZMH level, in BC and healthy women. 30 breast cancer patients, and 30 control women in premenopausal status, have participated in this study. GZMH, Estrogen levels, and ER,PR have been measured in cancer and healthy women subsequently, as using ELISA, Radioimmunoassay, and Immunohistochemistry methods. Mean GZMH value was lower in BC than healthy women [p<0.0001]. Our study has implicated suppressor existence, or the problem for producing of GZMH in patients group, and levels of estrogen that could not effect on making positive ER, PR

Distant subcutaneous recurrence of a parathyroid carcinoma: abnormal uptakes in the 99mTc-sestamibi scan and 18F-FDG PET/CT imaging

We report a rare case of distant subcutaneous parathyroid carcinoma recurrence. A 50-year-old woman was referred to our hospital because of sustained hypercalcemia despite surgical removal of a parathyroid carcinoma. A focal uptake in the upper mediastinal area was detected in a 99mTc-sestamibi scan, and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) imaging demonstrated a subcutaneous mass. She underwent tumor resection, and the pathological findings were consistent with a parathyroid carcinoma. The postoperative serum parathyroid hormone (PTH) level remained within normal limits. However, a new palpable solitary mass was identified in the upper portion of the left breast 1 year postoperatively. Both a 99mTc-sestamibi scan and 18F-FDG PET/CT imaging revealed an abnormal lesion in the upper breast, and subsequent pathology reports confirmed parathyroid carcinoma metastasis. Serum PTH and calcium levels fell within normal ranges after tumor resection. Two subcutaneous recurrent lesions appeared likely due to tumor seeding during the previous endoscopic operation at a local hospital.

Estudio de factores obstétricos, nutricionales y hormonales y su influencia en el desarrollo de cáncer de mama / Association between obstetric factors, hormone levels and nutritional status with the development of breast cancer

Background: Recent studies suggest that the age at first pregnancy, number of children and the lapse between births may protect against breast cancer. Furthermore, serum levels of estrogen, prolactin and progesterone appear to contribute to the development of this tumors in obese women. Aim: To verify whether the variables age at first pregnancy, number of children, birth interval, hormone levels and nutritional status are associated with the age at diagnosis of breast cancer. Material and Methods: Retrospective analysis of medical records of550female patients, diagnosed and treated for breast cancer at a hospital in Spain between 2009 and 2012. Results: We found a significant and positive association between age at diagnosis of cancer and the variables age at first pregnancy, parity and interval between pregnancies. There was also a significant correlation (p < 0.000) between serum levels of estrogen, prolactin and progesterone and nutritional status of patients. Conclusions: In this sample, age at first pregnancy or number of children, hormone levels and nutritional status are related to the age of onset of cancer.

Association between baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios and response to metronomic chemotherapy using cyclophosphamide and celecoxib in patients with advanced breast cancer.

BACKGROUND: Metronomic chemotherapy (MCT) with cyclophosphamide (Cy) and celecoxib (Cel) has therapeutic efficacy and low toxicity profile in advanced breast cancer patients (ABCP), but no reliable biomarkers of response have been found yet that allow patient selection for treatment. AIM: To investigate the potential role as biomarkers of pro‑ and antiangiogenic parameters and evaluate their response in ABCP receiving metronomic Cy 50 mg p.o./day + Cel 400 mg p.o./day. MATERIALS AND METHODS: Serum levels of vascular endothelial growth factor‑C (VEGF‑C), soluble VEGF receptors 2 and 3 (sVEGFR‑2, sVEGFR‑3), were measured at different time points in 13/15 patients included in a phase II trial of MCT with Cy+Cel. RESULTS: Serum levels of sVEGFR‑2 and sVEGFR‑3 increased significantly during treatment (P = 0.0392; P = 0.0066, respectively). VEGF‑C showed no significant modifications. Previous determinations of VEGF and TSP‑1 in the same patients were utilized. VEGF/sVEGFR‑2, VEGF/TSP‑1, and VEGF‑C/sVEGFR‑3 ratios decreased significantly along the treatment (P = 0.0092; P = 0.0072; P = 0.0141, respectively). Nonsignificant variations were observed for VEGF‑C/sVEGFR‑2 ratio. Baseline values of VEGF/sVEGFR‑2 and VEGF/TSP‑1 ratios were associated with time to progression (TTP) (P = 0.0407; P = 0.0394, respectively) meanwhile baseline VEGF was marginally significant (P = 0.0716). Patients with values lower than the 50th percentile for both ratios showed longer TTP. CONCLUSIONS: We have identified the baseline VEGF/sVEGFR‑2 and VEGF/TSP‑1 ratios as potential biomarkers of response in ABCP treated metronomically with Cy+Cel. This finding warrants its confirmation in a higher number of patients.

Terapia endocrina neoadyuvante en cáncer de mama, una alternativa de tratamiento e investigación / Neoadyuvant endocrine therapy in breast cancer

Neoadjuvant chemotherapy is an accepted strategyforpatients with locally advanced breast cáncer. This approach increases the possibilities ofconservative treatment and improves the resectability rates ofinitially unresectable tumors. In addition, preoperative systemic therapy allows the evaluation of prognostic and predictive factors, dynamically and in vivo. Since over 80% ofthese tumors express estrogen receptors (ER), endocrine therapy seems a logical treatment to employ in the neoadjuvant setting. The advent ofnew drugs that regúlate the ERfunction, along with the results of severa! clinical studies with the use of neoadjuvant endocrine therapy, support the feasibility and safety of utilizing this strategy before surgery. We herein analyze the available clinical evidence about the use of neoadjuvant therapy aiming to regúlate the activity ofthe ER. We also discuss the valué of predictive factors that could help the oncologist to select those patients most likely to benefit from this approach and the role of endocrine therapy as a research instrument.

Intron 4 VNTR (4a/b) Polymorphism of the Endothelial Nitric Oxide Synthase Gene Is Associated with Breast Cancer in Mexican Women

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population.

Influencia del estado nutricional, niveles hormonales séricos e historia familiar de cáncer en el desarrollo del cáncer de mama / Influence of nutritional status, hormones serum levels, and family history on breast cancer development

Background: Several studies have analyzed the relation between obesity and the hormonal imbalances generated by overweight and a family history of breast cancer. All of these factors are potentially implicated in the early development of breast cancer. Aim: To verify the existence of a significant relation between the nutritional status of breast cancer patients, their hormone serum levels (estrogens, prolactin, and progesterone), and the existence of a family history of breast cancer. Material and Methods: Retrospective data was collected from clinical records of524 women diagnosed with breast cancer in a Spanish hospital. Results: There was a positive association between estrogen, progesterone and prolactin serum levels and body mass index. The elevations in hormone levels occurred earlier in life among women with a family history of breast cancer. A two way ANOVA found a significant association between progesterone and prolactin levels with the age at diagnosis of breast cancer. Conclusions: Extreme serum levels of these hormones appear to be related to the early development of breast cancer, which in turn is influenced by the existence of a family history of cancer among those women with normal or average hormone levels.