Research Progress in the Role of Tamoxifen in Nervous System and Cognitive Function / 中国医学科学院学报

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

Predictores histopatológicos de respuesta a tratamiento en pacientes con cáncer de mama receptores hormonales positivos her2 negativo. Un estudio de centro único / Histopathological predictors of response to treat-ment in patients with hormone receptor positive her2 negative breast cancer. A single center study

In troducción: Una de cada 18 mujeres desarrolla a lo largo de su vida cáncer de mama, siendo esta la principal causa de muerte por cáncer en mujeres.El propósito del presente estudio fue establecer el valor predictivo de los factores histopatológicos presentes en tumores malignos de mama con recepto-res hormonales positivos Her2 negativo de un grupo de pacientes en un centro de referencia oncológico.Met odología: Este estudio longitudinal se realizó en el Instituto Oncológico Nacional "Dr Juan TancaMa-rengo", de Guayaquil -Ecuador. El período de inclusión del 2007 al 2009 con período de observación hasta diciembre del 2020. Con una muestra no probabilística, se incluyeron mujeres con cáncer de mama, hormonal positivo Her2Neu negativo, que hayan recibido tratamiento adyuvante durante un pe-riodo de seguimiento. Se midieron variables demográficas, clínicas, relacionadas al tumor, clasificación TNM y sobrevida.Se realiza un análisis univariado descriptivo de la muestra, un análisis bivariado, com-parando el grupo de pacientes fallecidas con el grupo de pacientes vivas; un análisis de correlación entre variables en escala; un análisis de supervivencia y finalmente se presenta una regresión COX para pre-decir la supervivencia en base a las variables.R esultados: Ingresaron al estudio 105 pacientes, de 54.1 ± 11.4 años. 58.1% de casos en etapa temprana y 41.9% en etapa localmente avanzada. La sobrevida global (SG) fue de 67.6%a 14 añosy la sobrevida librede progresión (SLP) del 59.05%. La terapia de bloqueo hormonal se asoció con la SLP (R=0.544, P<0.01) y con SG (R=0.399, P<0.05). El compromiso ganglionar en estadio N0 tuvo una SLP de 11.9 ± 0.4 años, en estadio N3 fue de 6.8 ± 1.6 años (P<0.01). El modelo de regresión de Cox para predecir el tiempo de vida libre de progresión o enfermedad fue estadísticamente significativo con la terapia de bloqueo hormonal (R2=0.607, P<0.001) Conclusión: Laterapia de bloqueo hormonal mantenida por más de 5 años tiene un impacto positivo en la supervivencia de las pacientes con cáncer de mama hormonal positivo Her2 Neu negativo

In troduction:One in 18 women develops breast cancer throughout her life, this being the leading cause of death from cancer in women. The purpose of the present study was to establish the predictive value of the histopathological factors present in malignant breast tumors with positive hormone receptors Her2 negative in a group of patients in an oncology reference center.Met hodology: This longitudinal study was conducted at the "Dr. Juan Tanca Marengo" National Oncology Institute in Guayaquil -Ecuador. The inclusion period was from 2007 to 2009, with an observation period until December 2020. With a non-probabilistic sample, women with hormone-positive Her2 Neu negative breast cancer who had received adjuvant treatment during a follow-up period were included. Demo-graphic, clinical, tumor-related, TNM classification and survival variables were measured. A descriptive univariate analysis of the sample is performed, a bivariate analysis comparing the group of deceased patients with the group of living patients; a correlation analysis between variables in scale; a survival analysis; and a COX regression is presented to predict survival based on the variables.R esults: 105 patients,54.1 ± 11.4 years old, entered the study. 58.1% of cases are in the early stage, and 41.9% are in a locally advanced stage. Overall survival (OS) was 67.6% at 14 years, and progression-free survival (PFS) was 59.05%. Hormone blocking therapy was associated with PFS (R=0.544, P<0.01) and OS (R=0.399, P<0.05). Lymph node involvement in stage N0 had a PFS of 11.9 ± 0.4 years; stage N3 was 6.8 ± 1.6 years (P<0.01). The Cox regression model to predict progression-free or disease-free life was statistically significant with hormone blockade therapy (R2=0.607, P<0.001).C o nclusion: Hormone blockade therapy maintained for more than five years positively impacts the sur-vival of patients with hormone-positive Her2 Neu negative breast cancer.

Adesão à Terapia Hormonal Adjuvante com Tamoxifeno e Anastrozol utilizando ARMS-12 e MMAS-4 / Adherence to Adjuvant Hormone Therapy with Tamoxifen and Anastrozole using ARMS-12 and MMAS-4 / Adherencia a la Terapia Hormonal Adyuvante con Tamoxifeno y Anastrozol utilizando ARMS-12 y MMAS-4

Introdução: Entre os cânceres de mama, aproximadamente 75% das mulheres são receptores hormonais positivos, sendo estas mais propensas a responderem à hormonioterapia com anastrozol e tamoxifeno. Apesar de eficazes, apresentam taxas significativas de não adesão. Objetivo: Avaliar a adesão à terapia hormonal adjuvante com tamoxifeno e anastrozol em pacientes atendidos nos Ambulatórios da Mastologia e de Quimioterapia do Hospital São Paulo entre os anos de 2019 e 2020. Método: Estudo transversal com 102 mulheres, realizado entre os meses de setembro de 2019 e março de 2020. A adesão à terapia hormonal adjuvante foi avaliada utilizando-se as escalas Morisky Medication Adherence Scale (MMAS-4) e Adherence to Refills and Medications Scale of 12 items (ARMS-12). Resultados: A média de idade foi de 61,5 anos (59,3-63,6). Entre as pacientes, 27,7% faziam uso de tamoxifeno e 72,3% de anastrozol. Relataram desconforto em relação ao uso do medicamento 84,4%, sendo as ondas de calor (42,2%) e as dores articulares (55,9%) os mais frequentes. A escala de ARMS>12 foi pontuada por 79,2%; cerca de 90% das mulheres pontuaram a MMAS-4 até dois pontos, porém não houve diferença significativa entre os tipos de hormônios utilizados para escalas de adesão (p=0,815 e p=0,489). Conclusão: A adesão à hormonioterapia observada foi relativamente baixa, independentemente da endocrinoterapia, podendo essas pacientes estarem em risco de inadequação quanto à resposta clínica

Introduction: Among breast cancers, approximately 75% of women are hormone receptors-positive, and these are more likely to respond to hormone therapy with anastrozole and tamoxifen. Although effective, they have significant rates of non-adherence. Objective: To evaluate adherence to adjuvant hormone therapy with tamoxifen and anastrozole in patients consulted at the Mastology and Chemotherapy Outpatient Clinic of Hospital São Paulo between 2019 and 2020. Method: Cross-sectional study carried out with 102 women between September 2019 and March 2020. Adherence to hormone therapy was evaluated using the Morisky Medication Adherence Scale (MMAS-4) and Adherence to Refills and Medications Scale of 12 items (ARMS-12). Results: The mean age was 61.5 years (59.3-63.6). Among the patients, 27.7% used tamoxifen and 72.3%, anastrozole. 84.4% of them reported discomfort in using the medication, the most frequent were hot flashes (42.2%) and joint pain (55.9%). 79.2% scored the ARMS>12 scale, about 90% of the women scored MMAS-4 up to 2 points, but there was no significant difference between the types of hormones used for adhesion scales (p=0.815 to p=0.489). Conclusion: Adherence to hormone therapy was relatively low, regardless of the hormone used, and these patients may be at risk of inadequate clinical response

Introducción: Entre los cánceres de mama, aproximadamente el 75% de las mujeres son receptores hormonales positivos, y estas son más propensas a responder a la terapia hormonal con anastrozol y tamoxifeno. Aunque son eficaces, tienen tasas significativas de no adherencia. Objetivo: Evaluar la adhesión a la terapia hormonal adyuvante con tamoxifeno y anastrozol en pacientes atendidas en las Clínicas Ambulatorias de Mastología y Quimioterapia del Hospital São Paulo entre 2019 y 2020. Método: Este es un estudio transversal realizado con 102 mujeres entre septiembre de 2019 y marzo de 2020. La terapia hormonal adjunta se evaluó utilizando las escalas Morisky Medication Adherence Scale (MMAS-4) e Adherence to Refills and Medications Scale of 12 items (ARMS-12). Resultados: La edad media fue de 61,5 años (59,3-63,6). Entre las pacientes, el 27,7% utilizaron tamoxifeno y el 72,3% anastrozol. El 84,4% de ellas reportaron molestias en relación con el uso del medicamento, siendo los más frecuentes los sofocos (42,2%) y el dolor articular (55,9%). 79,2% puntuaron la escala ARMS>12, alrededor del 90% de las mujeres obtuvieron MMAS-4 hasta dos puntos, pero no hubo diferencia significativa entre los tipos de hormonas utilizadas para escalas de adhesión (p=0,815 a p=0,489). Conclusión: La adherencia de la terapia hormonal observada fue relativamente baja, independientemente de la hormona utilizada, y estas mujeres pueden estar en riesgo de respuesta clínica inadecuada

Proliferación vascular atípica mamaria inducida por radioterapia / Atypical vascular proliferation of the breast induced by radiation

La proliferación vasculara típica mamaria inducida por radioterapia es una proliferación angiomatoide que aparece sobre la piel previamente irradiada por el tratamiento conservador de un carcinomademama. Se presenta el caso de una paciente de 58años que consultó por la aparición de múltiples pápulas purpúricas milimétricas en la mama derecha. Había recibido radioterapia y cuadrantectomía por un carcinoma intraductal 5años antes y estaba medicada con tamoxifeno. El análisis histópatológico e inmunohistoquímico informó: "Proliferación vascular atípica inducida por radiación, variedad atípica inducida por radiación, variedad linfática". Se adoptó una conducta expectante, con seguimiento estrecho.

Atypical vascular proliferation of the breast induced by radiation is an angiomatoid proliferation that appears on previously irradiated skin by the conservative treatament of a breast carcinoma. We present a 58-year-old female patient who consulted for multiple millimeter purpuric papules in the right breast. She received radiotherapy and quadrantectomy for an intraductal carcinoma 5 years before. She is currently on tomoxifen. The histopathology and immunohistochemistry reported atypical vascular proliferation induced by radiation, lymphatic variety. Watchuful waiting is adopted with close monitoring.

Ginecomastia: Consideraciones médicas y quirúrgicas en cirugía general / Gynecomastia: Medical and surgical considerations in general surgery

La ginecomastia, definida como el crecimiento del tejido glandular mamario en los hombres, aparece desde la etapa neonatal hasta la senil, puede ser unilateral o bilateral, y es de causa multifactorial, incluyendo aquellos pacientes asociados al uso de medicamentos, donde predomina un desbalance en la relación testosterona­estrógeno. Relativamente, la idiopática es la más frecuente. La mayoría involucionan espontáneamente, las neonatales por perdida del influjo transplacentario en las primeras semanas, y las puberales entre 12 a 24 meses. Se presenta como un aumento del tamaño mamario, asintomático o con hipersensibilidad por inflamación durante el crecimiento del tejido fibroglandular mamario, con una repercusión psicológica enorme, sobre todo en la etapa de la adolescencia. El estudio y manejo es interdisciplinario y se ofrece de acuerdo con las condiciones y la etiología. Aquellos pacientes púberes en quienes no involuciona reciben tratamientos médicos, o tratamientos quirúrgicos cuando falla la terapéutica o hay presión social, e incluso radioterapia en casos donde desarrollan ginecomastia con hipersensibilidad al tratamiento hormonal del cáncer de próstata

Gynecomastia, defined as the growth of breast glandular tissue in men, appears from the neonatal to senile stage, can be unilateral or bilateral, and is of multifactorial cause, including those patients associated with the use of medications, where an imbalance in the testosterone ­ estrogen ratio. Relatively, idiopathic is the most common. Most regress spontaneously, neonatals due to loss of transplacental influx in the first weeks, and pubertal ones between 12 to 24 months. It presents as an increase in breast size, asymptomatic or with hypersensitivity due to inflammation during the growth of the mammary fibroglandular tissue, with an enormous psychological repercussion, especially in adolescence. The study and management is interdisciplinary and offered according to conditions and etiology. Those pubertal patients in whom it does not regress receive medical treatments, or surgical treatments when therapy fails or there is social pressure, and even radiotherapy in cases where they develop gynecomastia with hypersensitivity to hormonal treatment of prostate cancer

Switching of hormone therapies in breast cancer women / Avaliação da mudança do esquema hormonioterápico em mulheres com câncer de mama

Abstract Objective The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. Methods This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. Results From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. Conclusion The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.

Resumo Objetivo O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. Métodos Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. Resultados De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. Conclusão O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razõesmais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.

Análise das alterações endometriais nas histeroscopias de pacientes em tratamento de câncer de mama com bloqueadores hormonais / Analysis of endometrial changes in the histeroscopies of patients treating breast cancer with hormonal blockers

Objetivo: analisar lesões endometriais de pacientes com câncer de mama em tratamento com Tamoxifeno® presentes nas histeroscopias e relacioná-las com a dose de medicamento utilizada, tempo de terapêutica, presença de lesões endometriais prévias e estado de pré ou pós menopausa. Método: estudo retrospectivo, transversal e analítico. Dados analisados pelo teste qui quadrado, p<0,05. Resultados: dentre as 75 histeroscopias analisadas, 12 eram normais (16%) e 63 apresentaram alteração endometrial (84%). Dentre os achados das histeroscopias, 49 foram pólipos endometriais (67.12%), 7 foram pólipos endocervicais (9.58%), 11 foram hiperplasia simples sem atipias (15.06%), 1 foi hiperplasia complexa sem atipias (1.36%), 1 foi hiperplasia complexa com atipias (1.36%), 2 foram leiomiomas (2.73%) e 2 foram adenocarcinoma endometrioide (2.73%). Conclusão: O Tamoxifeno® predispõe o aparecimento de lesões endometriais, que podem ser malignas. Nesse estudo, a incidência dessas lesões foi expressivamente maior do que os valores encontrados na literatura

Objective: To analyze the endometrial lesions in hysteroscopies of patients with breast cancer undergoing treatment with Tamoxifeno® and to relate them to the dose of medication used, time of therapy, presence of previous endometrial lesions and pre or postmenopausal status. Method: retrospective, cross-sectional and analytical study. Data were statistically analyzed using the chi-square test, p <0.05. Results: Among the 75 hysteroscopies analyzed, 12 were normal (16%) and 63 presented endometrial alteration (84%). Among the hysteroscopic findings, 49 were endometrial polyps (67.12%), 7 were endocervical polyps (9.58%), 11 were simple hyperplasia without atypias (15.06%), 1 was complex hyperplasia without atypias (1.36%), 1 was complex hyperplasia with atypia (1.36%), 2 were leiomyomas (2.73%) and 2 were endometrioid adenocarcinoma (2.73%). Conclusion: Tamoxifen predisposes the appearance of endometrial lesions, which may be malignant. In this study, the incidence of these lesions was significantly higher than the values found in the literature

Avaliação de risco cardiovascular e síndrome metabólica em mulheres com câncer de mama em uso de tamoxifeno / Evaluation of cardiovascular risk and metabolic syndrome in women with breast cancer using tamoxifen

Introdução: O câncer de mama é o segundo tipo de câncer mais comum no mundo e o mais comum entre as mulheres. Além disso, a doença cardiovascular é a causa mais comum de morte em mulheres. Objetivo: Avaliar os fatores de risco cardiovascular e de síndrome metabólica em mulheres com câncer de mama em uso de tamoxifeno. Métodos: Estudo transversal realizado com mulheres com diagnóstico prévio de câncer de mama. Para o diagnóstico da síndrome metabólica, foram utilizados os critérios da American Heart Association (2009). O risco cardiovascular foi avaliado pelo escore de risco de Framingham. Resultados: A frequência da síndrome metabólica é de 75% (n=24) dos participantes do estudo. A avaliação do risco cardiovascular mostrou que 18,7% (n=6) e 21,9% (n=7) das participantes apresentavam risco intermediário a alto, respectivamente. Conclusão: Conclui-se que mulheres em tratamento para câncer de mama apresentam alta prevalência de síndrome metabólica e fatores de risco cardiovascular, aumentando a mortalidade por doenças cardiovasculares neste grupo.

Introduction: Breast cancer is the second most common cancer in the world and the most common type among women. In addition, the cardiovascular disease is the most common cause of death in women. Objective: The objective was to assess cardiovascular risk factors and metabolic syndrome in women with breast cancer using tamoxifen. Methods: Cross-sectional study conducted with women with a previous breast cancer diagnosis. For metabolic syndrome diagnosis, the criteria established by the American Heart Association (2009) were used. Cardiovascular risk was assessed using the Framingham Risk Score Results: The frequency of metabolic syndrome is 75% (n=24) of the study participants. The cardiovascular risk assessment showed that 18.7% (n=6) and 21.9% (n=7) of the participants were at intermediate to high risk, respectively Conclusion: It is concluded that women undergoing breast cancer treatment have a high prevalence of metabolic syndrome and cardiovascular risk factors, increasing mortality from cardiovascular diseases in this group

Pubertad precoz periférica / Peripheral precocious puberty

Introducción: El síndrome de Mc Cune-Albright (SMA) es una rara entidad asociada con la displasia fibrosa poliostótica, con la presencia de manchas de color café con leche y también con la hiperfunción endocrina. La alteración hormonal más frecuente es la pubertad precoz. El SMA se debe a mutaciones activadoras del gen GNAS1. Objetivo: Describir las características clínicas de una paciente con síndrome de Mc Cune-Albright con una pubertad precoz. Métodos: Se realizó una revisión de la historia clínica como fuente primaria y fueron incorporados todos los elementos clínicos, bioquímicos, imagenológicos y genéticos que conformaron la valoración integral de la paciente. Presentación de caso: Se presenta un caso poco frecuente de síndrome de Mc Cune-Albright en una niña de siete años de edad con mamas Tanner II-III, sangrado vaginal, vello axilar y pubiano escaso, manchas café con leche y lesiones óseas. Lleva tratamiento con tamoxifeno, lo que ha logrado mantener frenada la progresión del desarrollo puberal. Conclusiones: Aunque esta entidad es de carácter benigno y la prevalencia es extremadamente baja, el inicio puberal precoz y el compromiso de la talla final pueden producir impacto psicológico en la calidad de vida y en el desarrollo normal del individuo(AU)

Introduction: Mc Cune-Albright syndrome (SMA, by its acronym in Spanish) is a rare entity associated with polyostotic fibrous dysplasia, with the presence of brown spots with milk and also with endocrine hyperfunction. The most common hormonal alteration is precocious puberty. SMA is caused by GNAS1 gene´s activator mutations. Objective: Describe the clinical characteristics of a patient with Mc Cune-Albright syndrome with precocious puberty. Methods: A review of the medical history was carried out as a primary source and all the clinical, biochemical, imaging and genetic elements that made up the comprehensive assessment of the patient were incorporated. Case presentation: A rare case of Mc Cune-Albright syndrome occurs in a seven-year-old girl with Tanner II-III breasts, vaginal bleeding, axillary and pubic hair, brown spots with milk and bone lesions. She is treated with tamoxifen, which has managed to keep the progression of pubertal development slow. Conclusions: Although this entity is benign in nature and the prevalence is extremely low, early pubertal onset and the compromise of the final size can have a psychological impact on the quality of life and normal development of the individual(AU)

Urinary incontinence and overactive bladder symptoms in women with breast cancer being treated with oral hormone therapy / Incontinência urinária e sintomas de bexiga hiperativa em mulheres com câncer de mama em tratamento com terapia hormonal oral

Abstract Objective: The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. Methods: The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. Results: Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. Conclusion: The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment.

Resumo Objetivo: O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. Métodos: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. Resultados: Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. Conclusão: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.

Caracterización de incontinencia urinaria en mujeres premenopáusicas con cáncer de mama en tratamiento con tamoxifeno por cinco años en el Instituto Nacional del Cáncer / Characterization of urinary incontinence in pre-menopausal women with breast cancer treated with tamoxifen for 5 years at the National Cancer Institute

INTRODUCCIÓN El cáncer de mama es el tipo de cáncer que se diagnostica con mayor frecuencia en mujeres y la segunda causa más común de muerte por cáncer en este género. Dentro de las indicaciones de tratamiento, se encuentran: cirugía, radioterapia, quimioterapia y terapia endocrina. Esta última se basa en el uso de tamoxifeno, cuyo uso de forma prolongada puede producir efectos secundarios como sequedad vaginal, ardor, irritación, picazón, disuria, incontinencia urinaria, entre otros OBJETIVO Caracterizar la incontinencia urinaria en mujeres premenopáusicas con cáncer de mama en tratamiento con tamoxifeno por 5 años en el Instituto Nacional del Cáncer MATERIAL Y MÉTODO Estudio descriptivo de corte transversal. Se incluyeron mujeres diagnosticadas con cáncer de mama inscritas y tratadas en el Instituto Nacional del Cáncer. Se aplicó cuestionario ICIQ ­SF a la población de estudio con el fin de caracterizar la presencia de incontinencia urinaria. Además, se calculó la proporción entre mujeres con incontinencia urinaria y nuliparidad/mujeres con incontinencia urinaria y paridad RESULTADOS Se evaluaron 15 pacientes. 93,33% presentaron incontinencia urinaria. El promedio de edad de mujeres con incontinencia urinaria fue de 51,21 (± 4,74) años. La razón de mujeres con nuliparidad/con paridad fue de 4:15 CONCLUSIÓN 99,33% de las pacientes presentaron incontinencia urinaria. Los resultados entregados en este estudio deben ser considerados como un elemento que contribuya a detectar la magnitud del problema en la población inscrita y tratada en el Instituto Nacional del Cáncer.

BACKGROUND Breast cancer is the type of cancer diagnosed most frequently in women, and the second most common cause of death from cancer in this gender. Within the indications of treatment, they are: surgery, radiotherapy, chemotherapy and endocrine therapy. The last is based on the use of tamoxifen, whose prolonged use can produce side effects such as vaginal dryness, burning, irritation, itching, dysuria, urinary incontinence, among others OBJECTIVE To characterize urinary incontinence in pre-menopausal women with breast cancer treated with tamoxifen for 5 years at the Instituto Nacional del Cáncer MATERIAL AND METHOD Descriptive cross-sectional study. We included women diagnosed with breast cancer enrolled and treated at the Instituto Nacional del Cáncer. The ICIQ -SF questionnaire was applied to the study population to characterize the presence of urinary incontinence. In addition, the proportion between women with urinary incontinence and nulliparity / women with urinary incontinence and parity was calculated RESULTS 93,33% presented urinary incontinence. The average age of women with urinary incontinence was 51,21 (± 4,74) years. The ratio of women with nulliparity / with parity was 4:15 CONCLUSION 99,33% of the patients presented urinary incontinence. The results delivered in this study should be considered as one element that helps to detect the magnitude of this problem in the population registered and treated in the Instituto Nacional del Cáncer. Keywords:

Nuevos avances en el conocimiento de la historia natural de la displasia fibrosa / News advances in the knowledge of natural history of the fibrous dysplasia

La displasia fibrosa (DF) es una enfermedad infrecuente del hueso, no hereditaria, producida por una mutación activadora del gen GNAS, responsable de codificar la unidad a-estimuladora de la proteína G (Gsa). La presentación clínica de la enfermedad es muy variada, pues adopta desde formas asintomáticas hasta otras marcadamente sintomáticas. En los últimos años, el análisis exhaustivo de bases de datos de pacientes con DF ha permitido conocer más sobre su historia natural. En este artículo se revisa la información actualmente disponible sobre algunos aspectos que ayudarán al mejor enfoque clínico del paciente, como son: la utilidad clínica de los marcadores óseos, los factores pronósticos para el desarrollo de fracturas, la DF como condición predisponente para el desarrollo de tumores específicos, nuevas perspectivas sobre la fisiopatología del dolor óseo y nuevas estrategias terapéuticas. Un mayor conocimiento sobre la historia natural de esta enfermedad finalmente redundará en la mejor calidad de vida de los pacientes con DF. (AU)

Fibrous dysplasia (FD) is an infrequent, non-hereditary bone disease caused by a somatic mutation of the GNAS gene, responsible for encoding the a-subunit of the G-protein (Gsa). The clinical presentation of the disease varies greatly, with some patients being asymptomatic and others markedly symptomatic. The exhaustive analysis of the database from patients with FD has allowed to learn more about the natural history of this disease. This article reviews the current information available on the clinical utility of bone markers, the prognostic factors for the occurrence of fractures, the evidence supporting as a predisposing condition for the development of specific tumors, new perspectives on the pathophysiology of bone pain, and emerging therapeutic strategies. A greater understanding of the natural history of this disease will allow to make better medical decisions, which will ultimately contribute to improve FD patients' quality of life. (AU)

Avaliação da adesão ao tratamento com Tamoxifeno por mulheres com câncer de mama / Tamoxifen treatment adherence assessment by women breast cancer / Evalución de adherencia al tratamento com Tamoxifeno em mujeres com cáncer de seno

Justificativa e objetivos: A terapia antineoplásica oral apresenta vantagens comparada a outras terapias para o tratamento do câncer, por ser administrada em domicílio, de forma simples e rápida, no entanto, essa terapia aumenta a responsabilidade do paciente em relação ao seu tratamento e a adesão é fundamental para a sua eficácia. Evidenciam-se poucos estudos referente ao acompanhamento farmacoterapêutico na terapia antineoplásica oral, nesses contexto, o presente estudo busca avaliar a adesão ao tratamento com tamoxifeno em mulheres com câncer de mama, antes e após acompanhamento farmacoterapêutico. Métodos: Trata-se de um estudo clínico randomizado e quantitativo. A coleta de dados foi realizada durante seis meses. A randomização aleatória dividiu-se em Grupo Controle e Grupo Acompanhamento, sendo o acompanhamento subdividido: Antes e Após o Acompanhamento. O Grupo acompanhamento recebeu mensalmente intervenções farmacêuticas individuais. A adesão foi avaliada pelo Brief Medication Questionnair e Problemas Relacionados aos Medicamentos quanto Necessidade, Efetividade e Segurança. Resultados: Após acompanhamento farmacêutico observou-se diferença entre os grupos Grupo Acompanhamento e Grupo Controle quanto à prática de atividade física (p=0,043), adesão ao tratamento (p=0,006), redução de efeitos adversos (p=0,003) e doenças associadas (p=0,002). Os Problemas Relacionados a Medicamentos mais frequentes foram de segurança e adesão, para os quais foram realizadas 54 intervenções farmacêuticas. As reações adversas descritas pelas pacientes acometiam principalmente sistema genital e trato gastrintestinal. Conclusão: Evidenciou-se que o acompanhamento farmacoterapêutico contribuiu efetivamente na adesão ao tratamento com tamoxifeno e as intervenções farmacêuticas realizadas contribuíram para prevenção e redução dos problemas associados a farmacoterapia.(AU)

Background and objectives: Oral antineoplastic therapy has advantages compared to other therapies for the treatment of cancer, because it is administered at home, in a simple and fast, however, this therapy increases the responsibility of the patient regarding its treatment and adherence is critical to its effectiveness. There are few studies on pharmacotherapeutic monitoring in oral antineoplastic therapy. In this context, the present study aims to evaluate to adherence with tamoxifen in women with breast cancer, before and after of pharmaceutical care. Methods: It is a randomized and quantitative clinical study. Data collection was performed during six months. Random randomization was divided into Control Group and Monitoring Group. The follow-up was subdivided: Before and After Monitoring. The Monitoring Group received monthly individual pharmaceutical interventions. Adherence was assessed by the Brief Medication Questionnaire and Drug Related Problems as Need, Effectiveness, and Safety. Results: There was a significant difference between the follow-up group and control group regarding physical activity (p = 0.043), adherence to treatment (p = 0.006), reduction of adverse effects (p = 0.003) and associated diseases (p = 0.002). The most frequent drug-related problems were safety and adherence, for which 54 pharmaceutical interventions were performed. The adverse reactions described by the patients mainly affected the genital system and the gastrointestinal tract. Conclusion: It was evidence the pharmaceutical care effectively contributed to the adherence to tamoxifen treatment and the performed pharmaceutical interventions contributed to the prevention and reduction of the problems associated with phamacoterapy.(AU)

Justificación y objetivo: La terapia antineoplásica oral presenta ventajas comparadas a otras terapias para el tratamiento del cáncer, por ser administrada a domicilio, de forma simple y rápida, sin embargo, esta terapia aumenta la responsabilidad del paciente en relación a su tratamiento y la adhesión es fundamental para su eficacia. Se evidencian pocos estudios referentes al seguimiento farmacoterapéutico en la terapia antineoplásica oral, en ese contexto, el presente estudio busca evaluar la adhesión al tratamiento con tamoxifeno en mujeres con cáncer de mama, antes y después de seguimento farmacoterapéutico. Métodos: Se trata de un estudio clínico aleatorizado y cuantitativo. La recolección de datos se realizó durante seis meses. La aleatorización aleatoria se dividió en Grupo Control y Grupo Seguimiento, siendo el acompañamiento subdividido: Antes y Después del Acompañamiento. El Grupo de seguimiento recibió mensualmente intervenciones farmacéuticas individuales. La adhesión fue evaluada por el Brief Medication Questionnair y los problemas relacionados con los medicamentos como la necesidad, la eficacia y la seguridad. Resultados: Después del seguimiento farmacéutico se observó diferencia entre los grupos Grupo Acompañamiento y Grupo Control en cuanto a la práctica de actividad física (p = 0,043), adhesión al tratamiento (p = 0,006), reducción de efectos adversos (p = 0,003) y enfermidades asociadas (p = 0,003) p = 0,002). Los problemas relacionados con los medicamentos más frecuentes fueron de seguridad y adhesión, para los que se realizaron 54 intervenciones farmacéuticas. Las reacciones adversas descritas por las pacientes acometieron principalmente sistema genital y tracto gastrointestinal. Conclusión: Se evidenció que el seguimiento farmacoterapéutico contribuyó efectivamente a la adherencia al tratamiento con tamoxifeno y las intervenciones farmacéuticas realizadas contribuyeron a la prevención y reducción de los problemas asociados con la farmacoterapia.(AU)

Uso de testosterona en mujeres: un comentario sobre el consenso global sobre el uso de la terapia de testosterona para mujeres / Global consensus position statement on the use of testosterone therapy for women

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)

There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)

Immunohistochemical assessment of symptomatic postmenopausal endometrial polyps in tamoxifen users and nonusers: a case control study

ABSTRACT BACKGROUND: Endometrial polyps are common in postmenopausal women, and the effect of tamoxifen use (a risk factor for endometrial polyps) on their pathogenesis is unclear. OBJECTIVES: To evaluate the expression of hormone receptors and markers for proliferation/apoptosis (Ki-67 and Bcl-2) in endometrial polyps in postmenopausal users and nonusers of tamoxifen. DESIGN AND SETTING: Cross-sectional analytical study in a tertiary-level academic hospital. METHODS: 46 women (14 tamoxifen users and 32 nonusers) with postmenopausal bleeding underwent hysteroscopic resection of endometrial polyps. Polyp samples were immunohistochemically assessed for detection of Ki-67, Bcl-2 and estrogen and progesterone receptors. RESULTS: Analysis on the glandular component of the polyps revealed progesterone receptor expression in the polyps of 96.9% of the nonusers of tamoxifen, and 92.3% of the tamoxifen users (P = 0.499). All polyps in nonusers and 92.3% of those in users were also positive for estrogen receptors (P = 0.295). Ki-67 was expressed in 75% of the polyps in the tamoxifen users and 82.8% of those in the nonusers. All endometrial polyps expressed Bcl-2. CONCLUSIONS: The immunohistochemical analysis on endometrial polyps demonstrated that, although tamoxifen is considered to be a risk factor for endometrial polyps, there were no significant differences in the expression of hormone receptors between users and nonusers of tamoxifen. There were no between-group differences in Ki-67 and Bcl-2 expression, and all patients displayed inhibition of apoptosis by Bcl-2, thus supporting the theory that polyps develop due to inhibition of apoptosis, and not through cell proliferation.

Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status / 한국유방암학회지

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer.METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis.RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188).CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Adherencia a hormonoterapia en pacientes con carcinoma ductal in situ de mama / Adherence to hormonal therapy in patients with ductal carcinoma in situ of the breast

Introducción Las pacientes con Carcinoma Ductal in Situ de mama (cdis) tienen mayor riesgo de desarrollar carcinoma invasor. Aquellas con receptores hormonales positivos se beneficiarían con hormonoterapia. El largo período de tratamiento y los efectos adversos asociados al mismo hacen dificultosa la adherencia. Objetivos El objetivo del presente trabajo es analizar la adherencia a la hormonoterapia en pacientes operadas por Carcinoma Ductal in Situ en el Hospital Universitario Austral. Material y método Es un estudio observacional, analítico, de corte transversal. Se incluyeron pacientes con diagnóstico de Carcinoma Ductal in Situ que fueron intervenidas quirúrgicamente en el Hospital Universitario Austral en el período comprendido entre el 24 de julio de 2000 y el 5 de julio de 2017. Los datos fueron recopilados a través de una encuesta. Resultados Se obtuvieron 100 encuestas. La adherencia fue del 82%. La misma no se modificó según edad, conocimiento de riesgos y beneficios del tratamiento, tipo y número de cirugías, radioterapia y número de consultas. Las reacciones adversas a la medicación fueron la causa más frecuente de abandono al tratamiento. Conclusiones El tratamiento multidisciplinario podría asegurar un óptimo nivel de adherencia

Introduction Patients with Ductal Carcinoma in Situ of the breast (dcis) have a higher risk of developing invasive carcinoma. Those with hormone receptor-positive would benefit from hormonal therapy. The long period of treatment and the associated adverse events make adherence difficult. Objectives The aim of this study is to analyze the adherence of hormonal therapy in operated patients with Ductal Carcinoma in Situ at Hospital Universitario Austral. Materials and method It is an observational, analytical and cross-sectional study. Patients diagnosed with Ductal Carcinoma in Situ who underwent surgery at Hospital Universitario Austral in the period between 07/24/2000 and 07/05/2017 were included. The data was collected through a survey. Results 100 surveys were obtained. The adherence was 82%. It was not modified according to age, knowledge of risks and benefits of the treatment, type and number of surgeries, radiotherapy and number of consultations. Adverse events were the most frequent cause of discontinue of treatment. Conclusions Multidisciplinary treatment could ensure an optimal level of adherence

Thick “Swiss Cheese” Appearance of Uterine Endometrium in Postmenopausal Women with Different Gynecologic Conditions

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

Prediction of Late Breast Cancer-Specific Mortality in Recurrence-Free Breast Cancer Survivors Treated for Five Years with Tamoxifen / 한국유방암학회지

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