Mamografía con contraste: nuestra experiencia / Contrast-enhanced digital mammography: our experience

Resumen La mamografía contrastada (CEDM, contrast-enhanced digital mammography) es una herramienta nueva que ha ido implementándose de forma creciente. Aparece como alternativa a la resonancia magnética (RM), y al igual que esta, tiene como principio el uso de contraste endovenoso para explorar la angiogénesis tumoral. Combina la imagen de mamografía convencional (Mx) con la técnica de sustracción con energía dual poscontraste, lo que resulta en un incremento en la detección de cáncer de mama, en un tiempo corto de estudio y a un bajo costo. Es un método prometedor en casos seleccionados y de fácil lectura, siendo útil principalmente en pacientes con diagnóstico de cáncer de mama para detectar lesiones adicionales y determinar el tamaño tumoral, ayudando en la planificación quirúrgica, así como también en la evaluación de la respuesta a la neoadyuvancia. También en el seguimiento de pacientes operadas, para caracterizar lesiones dudosas en Mx y ecografía, o como alternativa ante contraindicación de la RM. El objetivo de este trabajo es valorar la utilidad de la mamografía contrastada en la práctica diaria y determinar sus principales indicaciones. Repasamos con casos propios las utilidades y características del método.

Abstract Contrast-enhanced digital mammography (CEDM) is an emerging tool that has been increasingly implemented. It appears as an alternative to magnetic resonance imaging (MRI), using intravenous contrast to explore tumor angiogenesis. It combines conventional mammography (Mx) with post-contrast dual energy subtraction technique, resulting in increased detection of breast cancer, in a short study time and at a low cost. It is a promising method in selected cases and easy to read, being useful mainly in patients with breast cancer to detect additional lesions and determine the tumor size, that helps surgical planning, as well as in the evaluation of post-neoadjuvant chemotherapy response in the follow-up of patients treated with surgery, to address inconclusive findings in screening mammogram, or as an alternative when MRI is contraindicated. The purpose of this article is to assess the usefulness of contrasted mammography in daily practice and to determine its main indications. We review with our own cases the applications and characteristics of this method.

Efectos de la mastectomía en los parámetros baropodométricos de pacientes con cáncer de seno / The effect of mastectomy on baropodometric parameters for breast cancer patients / Efeitos da mastectomia nos parâmetros baropodometricos de pacientes com câncer de mama

Objetivo: la mastectomía posterior al cáncer de seno produce diversas alteraciones posturales y biomecánicas en el plano frontal y sagital. Dichos cambios conducen a una cinemática alterada de la columna vertebral, desequilibrio muscular y alteración del soporte del peso del pie. Este estudio pretende describir las alteraciones de la baropodometría después de la mastectomía, con base en análisis baropodométricos de la presión media y la carga estática. Metodología: se realizó un estudio descriptivo correlacional. Las propiedades de carga del pie se identificaron en 17 mujeres mastectomizadas. Se utilizó una placa de presión Ecosanit Foot para medir la carga del pie en posición anatómica y con los pies juntos. Resultados: en el estudio participaron 17 mujeres mastectomizadas con una edad media de 54.16 años. Las pacientes reportaron una presión media significativamente mayor en la posición anatómica del lado dominante mastectomizado en comparación con el lado no dominante mastectomizado (227.2 ± 22.16 vs. 175.6 ± 14.95, p =0.05). No hubo diferencia significativa para la carga estática entre el lado dominante mastectomizado y el lado no dominante mastectomizado en la posición anatómica (52.43±4.069 vs. 49.69 ± 4.094, de forma respectiva). Conclusión: los resultados actuales de nuestro estudio evidenciaron la distribución desequilibrada del peso (vector carga en el pie) en pacientes después de la mastectomía. Por tanto, en este texto se describen las alteraciones posturales, musculares, y el desequilibrio estático y dinámico en pacientes con cáncer de seno.

Objective: mastectomy after breast cancer produces several postural and biomechanical alterations in the frontal and sagittal plane. Such changes lead to disturbed kinematics of the spine, muscle imbalance and altered foot weight bearing. This study aims to describe body balance alterations after mastectomy based on the baropodometric analysis of their mean pressure and static load. Methodology: a descriptive correlational research was carried out. Foot weight-bearing properties were identified in 17 patients who have undergone a mastectomy. An Ecosanit Foot pressure plate was used to measure foot load at anatomical position and keeping the feet together. Results: 17 female patients who had undergo mastectomy with a mean age of 54.16 years took part on the research. Patients who have had a dominant-side mastectomy demonstrated significant greater mean pressure at anatomical position when compared to those patients who have had a non-dominant side mastectomy (227.2 ± 22.16 versus 175.6 ± 14.95, p =0.05). There was no significant difference for static load between the patients who have had a dominant side mastectomy and patients who have had a non dominant side mastectomy at anatomical position (52.43 ± 4.069 versus 49.69 ± 4.094, respectively). Conclusion: the current results of our research showed the unbalanced weight distribution in patients after mastectomy. Consequently, it describes the postural and muscular alterations, and the static and dynamic imbalance in breast cancer patients.

Objetivo: A mastectomia após câncer de mama produz diversas alterações posturais e biomecânicas nos planos frontal e sagital. Tais mudanças levam a alteração da cinemática da coluna, desequilíbrio muscular e alteração do suporte de peso do pé. Este estudo tem como objetivo descrever as alterações baropodométricas após mastectomia, com base em análises baropodométricas de pressão média e carga estática. Metodologia: foi realizado estudo correlacional descritivo. Propriedades de carga nos pés foram identificadas em 17 mulheres mastectomizadas. Uma placa de pressão Ecosanit Foot foi usada para medir a carga do pé em posição anatômica e com os pés juntos. Resultados: participaram do estudo 17 mulheres mastectomizadas com idade média de 54,16 anos. Os pacientes relataram uma pressão média significativamente maior na posição anatômica do lado mastectomizado dominante em comparação ao lado mastectomizado não dominante (227,2 ± 22,16 vs. 175,6 ± 14,95, p =0,05). Não houve diferença significativa para a carga estática entre o lado mastectomizado dominante e o lado mastectomizado não dominante na posição anatômica (52,43 ± 4,069 vs. 49,69 ± 4,094, respectivamente). Conclusão: Os resultados atuais do nosso estudo mostraram distribuição de peso desequilibrada (carga vetorial no pé) em pacientes após mastectomia. Portanto, este texto descreve alterações posturais, musculares e desequilíbrio estático e dinâmico em pacientes com câncer de mama.

Tendência da taxa de mortalidade por câncer de mama em mulheres com 20 anos ou mais no Brasil, 2005-2019 / Trend in breast cancer mortality rate among women aged 20 years or older in Brazil, 2005-2019

Resumo O objetivo é analisar a tendência da taxa de mortalidade por câncer de mama e sua correlação com o status de desenvolvimento socioeconômico no Brasil. Estudo ecológico de séries temporais realizado nos 26 estados, Distrito Federal e regiões do Brasil. As fontes de dados foram o Sistema de Informação sobre Mortalidade (número de óbitos), o Instituto Brasileiro de Geografia e Estatística (população residente) e o estudo da Carga Global de Doenças (socio-demographic index - SDI). Foram usados dados de 2005 a 2019. A tendência foi analisada pelos modelos de regressão de Prais-Winsten. A relação entre a taxa de mortalidade e o SDI foi analisada pelo coeficiente de correlação de Spearman. No período do estudo ocorrerem 207.683 óbitos por câncer de mama. A taxa padronizada de mortalidade média foi de 19,95 óbitos por 100.000 mulheres no Brasil. O Brasil e todas as regiões apresentaram tendência crescente da mortalidade. Do total de estados, 22 apresentaram tendência crescente. Verificou-se relação positiva entre a taxa de mortalidade e o SDI. A taxa de mortalidade padronizada por câncer de mama apresentou tendência crescente no Brasil, em todas as regiões e na maioria das unidades da federação. Verificou-se associação direta entre mortalidade e SDI, indicando maior magnitude em regiões mais desenvolvidas.

Abstract The aim is to analyze the trend in breast cancer mortality rates and its correlation with the socioeconomic development status in Brazil. It involved an ecological time series study carried out in the 26 units of the federation, Federal District and regions of Brazil. Data sources included the Mortality Information System (number of deaths), the Brazilian Institute of Geography and Statistics (resident population) and the study of the Global Burden of Disease (Socio-demographic Index - SDI). Data from 2005 to 2019 were used. The trend was analyzed using Prais-Winsten regression models. The relationship between the mortality rate and the SDI was analyzed using Spearman's correlation coefficient. During the study period, 207,683 deaths from breast cancer occurred. The average standardized mortality rate was 19.95 deaths per 100,000 women in Brazil. All the regions of Brazil showed an increasing trend in mortality. Of the total federative units, 22 showed an increasing trend. There was a positive relationship between the mortality rate and the SDI. The standardized mortality rate for breast cancer showed an increasing trend in Brazil, in all regions and in most states. There was a direct association between mortality and SDI, indicating a greater magnitude in more developed regions.

Occupational exposure to pesticides deregulates systemic cortisol levels in women with breast cancer and correlates with poor prognosis features

Pesticides have been pointed out as hormone disruptors and may significantly affect the prognosis of hormone-dependent diseases such as breast cancer (BC). Here, we investigated the impact of occupational pesticide exposure on systemic cortisol levels in female rural workers diagnosed with BC. Occupational exposure was assessed by interviews with a standardized questionnaire. Plasma samples (112 from pesticide-exposed women and 77 from unexposed women) were collected in the afternoon, outside the physiological cortisol peak, and analyzed by a chemiluminescent paramagnetic immunoassay for the quantitative determination of cortisol levels in serum and plasma. The results from both groups were categorized according to patients' clinicopathological and exposure data. BC pesticide-exposed women presented higher levels of cortisol than the unexposed. Higher cortisol levels were also detected in the exposed group with more aggressive disease (triple-negative BC), with tumors over 2 cm, with lymph node metastases, and with high risk of disease recurrence and death. These findings demonstrated that there is an association between pesticide exposure and BC that affected cortisol levels and correlated to poor disease prognosis.

Aporte espiritual/religioso pela enfermagem no tratamento do câncer de mama: revisão integrativa / Spiritual/religious support for nursing in the treatment of breast cancer: integrative review / Apoyo espiritual/religioso de la enfermería en el tratamiento del cáncer de mama: revisión integrativa

Objetivo: analisar na literatura científica a importância da abordagem espiritual/religiosa pela equipe de enfermagem no tratamento do câncer de mama. Método: revisão integrativa, realizada na BDENF, LILACS e SCOPUS. Resultados: foram selecionados seis estudos, evidenciou-se que a abordagem espiritual/religiosa pelos profissionais de enfermagem auxilia para o enfrentamento positivo do câncer de mama. Assim, emergiu a categoria.: Abordagem espiritual/religiosa na assistência de enfermagem e suas repercussões positivas para o enfrentamento do câncer de mama. Conclusão: a categoria da enfermagem integra a rede de apoio social para o alívio do sofrimento, por meio do aporte espiritual/religioso, auxiliando para a minimização de sentimentos negativos associados ao diagnóstico e aos eventos adversos dos tratamentos, sendo importante incluir discussões acerca desta temática na formação de nível técnico e graduação em enfermagem.

Objective: to analyze in the scientific literature the importance of the spiritual/religious approach by the nursing team in the treatment of breast cancer. Method: integrative review, carried out in BDENF, LILACS and SCOPUS. Results: six studies were selected, showing that the spiritual/religious approach by nursing professionals helps to cope positively with breast cancer. Thus, the following category emerged: Spiritual/religious approach in nursing care and its positive repercussions for coping with breast cancer. Conclusion: the nursing category is part of the social support network for relieving suffering, through spiritual/religious support, helping to minimize negative feelings associated with the diagnosis and adverse treatment events, and it is important to include discussions on this topic in technical and undergraduate nursing training.

Objetivos:analizar la importancia del abordaje espiritual/religioso por el equipo de enfermería en el tratamiento del cáncer de mama en la literatura científica. Método: revisión integradora, realizada en BDENF, LILACS y SCOPUS. Resultados: fueron seleccionados seis estudios que demuestran que el abordaje espiritual/religioso por profesionales de enfermería ayuda a enfrentar positivamente el cáncer de mama. Surgió la siguiente categoría: Enfoque espiritual/religioso en los cuidados de enfermería y sus repercusiones positivas para el afrontamiento del cáncer de mama. Conclusión: la categoría de enfermería forma parte de la red de apoyo social para aliviar el sufrimiento, a través del apoyo espiritual/religioso, ayudando a minimizar los sentimientos negativos asociados al diagnóstico y a los eventos adversos de los tratamientos, siendo importante incluir discusiones sobre este tema en la formación técnica y de pregrado de enfermería.

Neuroendocrine breast carcinoma

ABSTRACT Neuroendocrine breast cancer (NEBC) is a rare and heterogeneous entity. It most commonly presents a luminal phenotype and a worse prognosis. When diagnosed in an advanced stage, metastasis from another neuroendocrine tumor should be excluded. This case features a premenopausal woman with an oligometastatic breast large cell neuroendocrine carcinoma, estrogen receptor (ER) positive, and human epidermal growth factor receptor 2 (HER2) negative. Since the patient was very symptomatic at the presentation of the disease, chemotherapy was started. Complete radiological response of the metastatic disease was achieved, and the patient was then submitted to radical breast surgery and bilateral oophorectomy. She subsequently underwent radiation therapy. Since then and to date, she has been under endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i), with no evidence of malignant disease. Evidence to guide the choice of treatment for these tumors is currently scarce. In cases with oligometastatic disease, radical treatment should be considered. Given that this entity is rare, its reporting should be encouraged.

Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities

Background Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted 0protein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. Results We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV- MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. Conclusions As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.

Cost-utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in the second-line treatment for HER2-positive metastatic breast cancer / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan（T-DXd） versus trastuzumab emtansine （T-DM1） in the second-line treatment of HER2-positive metastatic breast cancer， and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast03， a partitioned survival model was constructed， with a cycle of 3 weeks as the simulation of patients’ lifetime. The incremental cost-effectiveness ratio （ICER） was calculated by using quality-adjusted life years （QALY） as output indicators， and sensitivity analysis was used to verify the robustness of the basic analysis results； the cost-effectiveness of the second-line treatment for HER2-positive metastatic breast cancer was compared between T-DXd and T-DM1. RESULTS Under the premise of taking 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay threshold （257 094 yuan/QALY）， the T-DXd group also needed to pay more cost compared with T-DM1 group while obtaining incremental utility （0.69 QALYs）， and the ICER value was 1 850 478.40 yuan/QALY. The results of univariate sensitivity analysis showed that progression-free survival state utility value， T-DXd price， cost discount rate were factors that had a great influence on ICER value， but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis， when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY， the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China’s per capita GDP as the WTP threshold， compared with T-DM1， T-DXd is not cost-effective in the second-line treatment of HER2-positive metastatic breast cancer.

Experience of LIN Yi in Disease-Syndrome-Syptom Differentiation and Treatment of Breast Cancer in Consolidation Phase / 中医杂志

This article summarized the clinical experience of Professor LIN Yi in applying the idea of disease-syndrome-syptom combination to the differentiation and treatment of breast cancer in consolidation phase. It is believed that the fundamental pathogenesis of breast cancer in consolidation phase is deficiency of healthy qi， so the treatment should emphasize on reinforcing healthy qi as the main and eliminating pathogen as the supplement. Commonly， Sijunzi Decoction （四君子汤）， Shenling Baizhu Powder （参苓白术散）， and Liuwei Dihuang Decoction （六味地黄汤） are used as the basic formula to strengthen the spleen and kidney to reinforce healthy qi， and Baihua Sheshe Cao （Scleromitrion diffusum ［Willd.］ R.J.Wang）， Yiyiren （Coix lacryma-jobi L.）， and ezhu （Curcuma aromatica Salisb.） are used to eliminate cancer toxin. It is also believed that the biological characteristics of different molecular subtypes of breast cancer are of great significance to the syndrome differentiation and treatment in traditional Chinese medicine， therefore， the formulas used in clinical practice are often selected taking into considerations of molecular subtypes of breast cancer. For those with positive sex hormone receptor， the most important thing is to replenish the congenital and benefit kidney essence， with modified Baihua Qiqi Decoction （白花芪杞汤）； for those with negative sex hormone receptor， the first step is to strengthen spleen and replenish kidneys， and it is especially important to strengthen the spleen with Baihua Qiling Decoction （白花芪苓汤）. At the same time， it is suggested that the primary and the secondary symptoms of patients should be differentiated， and the diseases and symptoms， as well as the modern medical laboratory indicators should be combined to give suitable medication.

Caracterización de los resultados de biopsia por trucut en pacientes con BI-RADS 4 y 5 sin criterio quirúrgico

Introducción: La biopsia percutánea se ha convertido, en nuestros días, en el método diagnóstico más utilizado para la evaluación de las lesiones de mama sospechosas de malignidad. Objetivo: Caracterizar los resultados de biopsia por trucut en pacientes con categorías BI-RADS 4 y 5 sin criterio quirúrgico. Materiales y métodos: Se realizó un estudio observacional, descriptivo y transversal de 70 pacientes que presentaron lesión sospechosa de malignidad por ultrasonografía y que requirieron la realización de biopsia por aguja gruesa de la imagen reportada, entre enero de 2019 y diciembre de 2020. Se realizaron en la Consulta de Intervencionismo Mamario del Departamento de Imagenología del Hospital Universitario Clínico Quirúrgico Comandante Faustino Pérez Hernández, de Matanzas. Se analizaron las variables edad, categoría BI-RADS, resultado histopatológico, tamaño tumoral y complicaciones. Resultados: El grupo etario predominante fue el de 70-79 años (27,1). Se clasificaron 48 pacientes con categoría BI-RADS 5, para un 68,6 %. El carcinoma ductal infiltrante resulto ser el tipo histológico predominante, con 40 pacientes, representando el 57,1 % del total. Se obtuvo una media de 28,91 mm de diámetro de las lesiones biopsiadas. Todas las muestras resultaron útiles, aun en diámetros transversales inferiores a 2 cm. En la serie, las complicaciones reportadas fueron escasas. Conclusiones: La biopsia realizada con aguja gruesa bajo guía ecográfica con técnica de manos libres, es un método confiable para el diagnóstico de cáncer de mama, seguro y sin complicaciones graves. Se confirma que la categoría BI-RADS 5 coincide con diagnóstico histopatológico de cáncer mamario.

Introduction: Percutaneous biopsy has become, nowadays, the most used diagnostic method to evaluate breast lesions suspected of malignancy. Objective: To characterize the Tru-cut biopsy results in patients with BI-RADS 4 and 5 categories without surgical criteria. Materials and methods: An observational, descriptive and cross-sectional study was carried out between January 2019 and December 2020 on 70 patients who presented who presented a lesion suspicious of malignancy by ultrasonography and required a thick-needle biopsy of the reported image. They were performed at the Breast Intervention Clinic of the Imaging Department of the Clinical Surgical University Hospital Comandante Faustino Pérez Hernández, from Matanzas. The variables age, BI-RADS category, histopathological result, tumor size and complications were analyzed. Results: The predominant age group was the 70-79 years-old one (27.1). 48 patients were classified with BI-RADS 5 category, for 68.6%. Infiltrating ductal carcinoma resulted the predominant histological type, with 40 patients representing 57.1% of the total. An average diameter of 28.91 mm was obtained from the biopsied lesions. All samples were useful, even in transverse diameters less than 2cm. In the series, few complications were reported. Conclusion: Biopsy performed with thick needle under ultrasound guidance with free-hands technique, is a reliable method for breast cancer diagnosis, safe and without serious complications. It is confirmed that BI-RADS 5 category coincides with breast cancer pathological diagnosis.

Tendencias de la mortalidad femenina por cáncer de mama en Argentina, 2005-2020 / Female breast cancer mortality trends in Argentina, 2005-2020

Introducción: El cáncer de mama es una causa de muerte evitable en las mujeres de hasta 74 años de edad. Sin embargo, es el cáncer más frecuente y la primera causa de muerte por tumores en esa población. Objetivo: Analizar las tendencias de la mortalidad por cáncer de mama en las mujeres de Argentina entre 2005 y 2020, considerando el grupo de edad y la región geográfica. Método: Estudio cuantitativo y descriptivo con perspectiva sociodemográfica. Se calcularon tasas específicas de mortalidad a partir de datos oficiales y se aplicaron modelos de regresión joinpoint para evaluar su tendencia temporal. Resultados: La tasa de mortalidad ajustada por cáncer de mama disminuyó significativamente (PPCA: −1,5%; IC95%: −1,3% a −0,7%); sin embargo, aumentó en las mujeres de 25 a 34 años (PPCA: 2,3%; IC95%: 1,4% a 3,2%). El descenso registrado se trasladó mayormente a las regiones Centro, Cuyo y Noroeste, mientras que las tasas de mortalidad de las regiones Noreste y Patagónica no variaron significativamente. Conclusiones: No obstante los progresos documentados, se evidencian desafíos para reducir la mortalidad por cáncer de mama en las poblaciones más jóvenes. Asimismo, persisten las desigualdades regionales, lo que destaca la importancia de adaptar las acciones a las necesidades del territorio.

Background: Breast cancer is a preventable cause of death among women up to 74 years of age. However, it is the most common cause of cancer death among this population. Objective: To analyze female breast cancer mortality trends in Argentina between 2005 and 2020, taking into account age groups and geographical regions. Method: Quantitative and descriptive study carried out from a socio-demographic perspective. Specific mortality rates were calculated based on official data, and joinpoint regression models were applied to evaluate time trends in mortality. Results: The adjusted mortality rate attributed to breast cancer decreased significantly (AAPC: −1,5%; CI95%: −1,3% to −0,7%); however, it increased among women aged 25-34 (AAPC: 2,3%; CI95%: 1,4% to 3,2%). Besides, the decreasing of mortality took place mainly in Central, Cuyo and Northwest regions meanwhile the mortality rates from Northeast and Patagonia regions didnt vary significantly. Conclusions: Although progress has been made, there are still some challenges regarding the reduction of breast cancer mortality in young women. In addition, regional disparities remain, highlighting the importance to adapt actions to territorial needs.

Differential Effect of ITE on the Aryl Hydrocarbon Receptor Signaling in Breast Cancer Tissue: A Histopathological Study / Efecto Diferencial de ITE en la Señalización del Receptor de Hidrocarburo de Arilo en Tejido de Cáncer de Mama: Un Estudio Histopatológico

SUMMARY: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in various types of cancers including breast cancer. However, the role of AhR with its endogenous ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the progression of breast cancer remains poorly understood. We aimed to investigate cell proliferation and migration states in breast cancer after activating AhR with the endogenous ligand ITE. Breast cancer tissue was evaluated by cell lines, immunohistochemistry, reverse transcription-polymerase chain reaction, cell proliferation, flow cytometry, migration assays and western blot techniques. We found that AhR was widely expressed in breast cancer tissues and metastasis lymph node tissues, but not in normal tissues. The expression AhR was independent between the age, grades and TNM classifications for breast cancer tissues. ITE treatment significantly induced the activation of AhR in a time-dependent manner in both MCF-7 and T47D breast cancer cell lines. Meanwhile, ITE did not affect the cell migration but significantly suppressed the cell proliferation in estrogen receptor positive (ER+) MCF-7 andT47D cells, which probably attribute to the induction of cell cycle arrest in G1 phase and shortened S phase. Further mechanism study showed that ERK1/2 and AKT signaling were required for the activation of AhR in MCF-7 cells. These data suggest that AhR is a potential new target for treating patients with breast cancer. ITE may be more potentially used for therapeutic intervention for breast cancer with the kind of ER(+).

El receptor de hidrocarburo de arilo (AhR) es un factor de transcripción activado por ligando que se expresa en gran medida en varios tipos de cáncer, incluido el cáncer de mama. Sin embargo, el papel de AhR con su ligando endógeno 2- (1'H-indol-3'-carbonil)-tiazol-4-ácido carboxílico metil éster (ITE) en la progresión del cáncer de mama sigue siendo poco conocido. Nuestro objetivo fue investigar la proliferación celular y los estados de migración en el cáncer de mama después de activar AhR con el ligando endógeno ITE. El tejido de cáncer de mama se evaluó mediante líneas celulares, inmunohistoquímica, reacción en cadena de la polimerasa con transcriptasa inversa, proliferación celular, citometría de flujo, ensayos de migración y técnicas de transferencia Western. Descubrimos que AhR se expresó ampliamente en tejidos de cáncer de mama y en linfonodos con metástasis, pero no en tejidos normales. La expresión AhR fue independiente entre la edad, grados y clasificaciones TNM para tejidos de cáncer de mama. El tratamiento con ITE indujo significativamente la activación de AhR de manera dependiente del tiempo en las líneas celulares de cancer de mama MCF-7 y T47D. Mientras tanto, ITE no afectó la migración celular, pero suprimió significativamente la proliferación celular en células MCF-7 y T47D con receptor de estrógeno positivo (ER+), lo que probablemente se atribuye a la inducción de la detención del ciclo celular en la fase G1 y la fase S acortada. Un estudio adicional del mecanismo mostró que las señales de ERK1/2 y AKT eran necesarias para la activación de AhR en las células MCF-7. Estos datos sugieren que AhR es un nuevo objetivo potencial para el tratamiento de pacientes con cáncer de mama. ITE puede ser utilizado más potencialmente en la intervención terapéutica para el cáncer de mama con el tipo de ER (+).

Alternativas de reconstrucción mamaria inmediata

La mastectomía total por cáncer de mama produce una deformidad importante en las pacientes, con alteraciones severas de su autoestima, imagen corporal, sexualidad, y calidad de vida en general. El gold estándar en los países desarrollados es la reconstrucción mamaria inmediata y, actualmente existen pocas contraindicaciones absolutas para realizar alguna técnica de reconstrucción. Este artículo se describen las opciones reconstructivas (colgajos e implantes), tiempos de reconstrucción, ventajas y desventajas de ambas técnicas, potenciales complicaciones, y se propone un algoritmo de tratamiento. La elección de la técnica de reconstrucción debería ser decidida entre la paciente y su cirujano/a, considerando características físicas, factores relacionados con la enfermedad y tratamiento oncológico, y preferencias de las pacientes.

Total mastectomy for breast cancer treatment can be a cause of deformity and distress for patients, with severe impairment of self-esteem, body image, sexuality, and quality of life. In developing countries, immediate breast reconstruction is the gold standard, and there are only a few absolut contraindications for some technique of breast reconstruction. This article describes reconstructive options (flaps and allo-plastic material), reconstructive timing, pros and cons of both techniques, potential complications, and an algorithm of treatment is proposed. Choice of the reconstructive technique should be decided by the patient and her surgeon, considering physical characteristics, factors related with the disease and oncologic treatments, and patients' preferences.

Programmed cell death protein 1 is a marker for neoadjuvant chemotherapy response in triple-negative breast cancer

SUMMARY OBJECTIVE: Tumor-infiltrating lymphocytes are detectable in up to 75% of triple-negative breast cancer. The composition of these infiltrates may influence prognosis and is not known regarding regulatory or effector lymphocytes. The objectives of this study were to describe and quantify the composition of the tumor-infiltrating lymphocytes before and after chemotherapy (neoadjuvant chemotherapy) and to evaluate their association with complete pathological response and overall survival. METHODS: This was a retrospective observational study. Clinical and pathological data from 38 triple-negative breast cancer patients treated with neoadjuvant chemotherapy at the University Hospital (HUCFF/UFRJ), between November 2004 and November 2018, were analyzed. The Stromal tumor-infiltrating lymphocytes (Stromal tumor-infiltrating lymphocytes) have been identified on hematoxylin and eosin-stained sections according to the guidelines of the "International tumor-infiltrating lymphocytes Working Group." Immunohistochemistry studies were performed to identify T-cell subsets (i.e., CD3, CD4, CD8, and FOXP3) and T-cell exhaustion (i.e., programmed cell death protein 1). RESULTS: Statistically significant changes in stromal tumor-infiltrating lymphocyte categories were observed before and post-neoadjuvant chemotherapy, with 32% of intermediate cases becoming high. The correlation between pre-neoadjuvant chemotherapy stromal tumor-infiltrating lymphocytes and pathological response, pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy, and stromal tumor-infiltrating lymphocytes and overall survival was not statistically significant. However, we noticed an increase of cells that favor the antitumor activity (i.e., CD3, CD8, and CD8/FOXP3 ratio) and decreased levels of cells inhibiting tumor activities (i.e., FOXP3 and programmed cell death protein 1) post-neoadjuvant chemotherapy. Importantly, programmed cell death protein 1 expression pre-neoadjuvant chemotherapy showed an association with pathological response. CONCLUSION: In this study, we observed that chemotherapy significantly increases stromal tumor-infiltrating lymphocytes, CD8 T cells, as well as CD8/FoxP3 ratio. Most importantly, programmed cell death protein 1 expression before neoadjuvant chemotherapy positively correlates with pathological response suggesting the use of programmed cell death protein 1 as a prognostic marker before neoadjuvant chemotherapy.

Aplicativo para tratamento do linfedema de membros superiores / Upper limb lymphedema treatment application

Introdução: O linfedema secundário se desenvolve comumente devido a um trauma no sistema linfático, podendo ocorrer após cirurgia de câncer. O aplicativo móvel é um meio de atualização técnico-científica de fácil acesso e de baixo custo que pode auxiliar o profissional de saúde a proporcionar o melhor tratamento para o paciente. O objetivo desse estudo foi construir um aplicativo para tratamento de linfedema de membros superiores. Método: A construção do aplicativo ocorreu em quatro etapas: (1) Concepção, envolvendo a identificação das necessidades do desenvolvimento do aplicativo; (2) Elaboração do conteúdo, incluindo a revisão integrativa da literatura nas principais bases de dados; (3) Construção, consistindo na estruturação do banco de dados e desenvolvimento do software; e (4) Transição, compreendendo a realização de testes de funcionalidade. Resultados: O aplicativo desenvolvido (Linfedema APP) é composto por 31 telas, 4 figuras e 3 vídeos. Ele foi registrado no Instituto Nacional da Propriedade Industrial (INPI) do Ministério do Desenvolvimento, Indústria e Comércio Exterior e está disponível gratuitamente na Google Play Store. Conclusão: Após a revisão integrativa da literatura nas principais bases de dados, foi desenvolvido o aplicativo "Linfedema APP", o qual se constitui em ferramenta prática para qualificar, direcionar e guiar o fisioterapeuta na realização dos exercícios nas pacientes pós- mastectomizados com linfedema em membros superiores.

Introduction: Secondary lymphedema commonly develops due to trauma to the lymphatic system, and may occur after cancer surgery. The mobile application is an easily accessible and low-cost means of technical-scientific updating that can help the health professional to provide the best treatment for the patient. Thus, the objective of this study was to build an application for the treatment and prevention of upper limb lymphedema. Methods: The construction of the application took place in four stages: (1) Conception, involving the identification of application development needs; Content development, including an integrative literature review in the main databases; (3) Construction, consisting of structuring the database and developing the software; and (4) Transition, comprising carrying out functionality tests. Results: The developed application (Linfedema APP) consists of 31 screens, 4 figures and 3 videos. It was registered at the National Institute of Industrial Property (INPI) of the Ministry of Development, Industry and Foreign Trade, and is available for free on the Google Play Store. Conclusion: After an integrative review of the literature in the main databases, the "Lymphedema APP" application was developed, which constitutes a practical tool to qualify, direct and guide the physiotherapist in performing the exercises in post-mastectomized patients with lymphedema in the upper limbs.

Aspectos clínicoepidemiológicos de pacientes con cáncer de mama del Policlínico 28 de septiembre / Clinical-Epidemiological Aspects of Patients with Breast Cancer and from the Policlínico 28 de Septiembre of Santiago de Cuba

Introducción: El cáncer de mama es considerado como un serio problema de salud pública por la alta prevalencia tanto en países desarrollados como en desarrollo. Son escasos los estudios clínico-epidemiológicos actualizados en el área de salud del Policlínico 28 de septiembre relacionados con dicha entidad clínica. Objetivo: Caracterizar desde el punto de vista clínico y epidemiológico a pacientes con cáncer de mama del área de salud perteneciente al Policlínico 28 de septiembre. Métodos: Estudio descriptivo en una serie de 35 mujeres mayores de 30 años con diagnóstico confirmado de cáncer de mama. Las variables estudiadas comprendieron edad, antecedentes familiares de cáncer de mama, factores de riesgo generales y hormonales, signos y síntomas clínicos, resultados de estudio ecográfico y diagnóstico histopatológico. Se utilizó el porcentaje como medida de resumen. Resultados: El 42,8 por ciento de la muestra objeto de estudio estuvo comprendido en el grupo de edad de 40-49 años. El 65,7 por ciento del total de mujeres tenía antecedentes familiares de cáncer de mama. La menarquía precoz (54,2 por ciento) y la nuliparidad (48,5 por ciento) representaron los factores de riesgo de mayor incidencia. El 57,1 por ciento de las lesiones diagnosticadas correspondieron a carcinomas en estadío I y IIa. Conclusiones: El cáncer de mama constituye un serio problema de salud en mujeres mayores de 30 años pertenecientes al Policlínico 28 de septiembre del municipio Santiago de Cuba(AU)

Introduction: Breast cancer is considered a serious public health concern due to its high prevalence in both developed and developing countries. There are few updated clinical-epidemiological studies carried out in the health area of the Policlínico Docente 28 de Septiembre related to this clinical entity. Objective: To characterize, from the clinical and epidemiological point of view, the patients with breast cancer and from the health area belonging to the Policlínico Docente 28 de Septiembre. Methods: A descriptive study was carried out with a series of 35 women aged more than 30 years and with a confirmed diagnosis of breast cancer. The variables studied included age, family history of breast cancer, general and hormonal risk factors, clinical signs and symptoms, ultrasound findings and histopathological diagnosis. Percentage was used as summary measure. Results: 42.8 percent of the study sample was in the age group 40-49 years old. Of the total number of women, 65.7 percent had a family history of breast cancer. Early menarche (54.2 percent) and nulliparity (48.5 percent) represented the risk factors with the highest incidence. 57.1 percent of the diagnosed lesions corresponded to stage I and IIA carcinomas. Conclusions: Breast cancer is a serious health problem in women older than 30 years and belonging to the Policlínico Docente 28 de Septiembre, of Santiago de Cuba Municipality(AU)

Repercusión de la pandemia COVID-19 en el diagnóstico y tratamiento del cáncer de mama en pacientes asistidas en la Unidad de Mastología del Hospital de Clínicas

Introducción: la crisis sanitaria por COVID-19 impactó en la atención de diversas patologías, entre ellas, el cáncer. Con el fin de disminuir el riesgo de contraer SARS-CoV-2 se redujo el número de consultas, lo que determinó un aumento en la tasa de morbilidad y mortalidad para otras patologías, lo que se ha denominado la "segunda pandemia". Objetivo: describir la actividad asistencial de la Unidad de Mastología (UM) en el período marzo 2020 - marzo 2022 y compararla con la del período marzo 2019 - marzo 2021. Objetivo: describir la actividad asistencial de la Unidad de Mastología (UM) en el período marzo 2020 - marzo 2022 y compararla con la del período marzo 2019 - marzo 2021. Material y método: estudio observacional retrospectivo que incluyó a pacientes asistidas por cáncer de mama (CM) en el período marzo 2019 - marzo 2022. Resultados: durante el año previo a la pandemia se asistieron 30 nuevas pacientes. En cuanto al tiempo entre el diagnóstico anatomopatológico y el primer tratamiento, en 73,3% fue ≤ 2 meses, 16,6% > 2 meses y ≤ 4 meses y en 10% fue > 4 meses. Durante la pandemia se asistieron 50 pacientes nuevas, lo que se traduce en un descenso de 16,6%. En cuanto al tiempo entre el diagnóstico anatomopatológico y el primer tratamiento: en 41% fue ≤ 2 meses, 33% > 2 meses y ≤ 4 meses y en 25% fue > 4 meses. Conclusiones: si bien se logró mantener la actividad asistencial y dar continuidad a la mayoría de los tratamientos, durante la pandemia COVID-19 se redujo el número de pacientes derivadas al servicio en aproximadamente 16,6% y se produjo un aumento en el tiempo transcurrido entre el diagnóstico y el primer tratamiento.

Introduction: the COVID-19 health crisis had a significant impact on the management of various pathologies, including cancer. To reduce the risk of contracting SARS-CoV-2, the number of consultations was reduced, leading to increased morbidity and mortality rates for other pathologies, which has been referred to as the "second pandemic." Objective: The aim of this study is to describe the clinical activity of the Breast Unit (BU) during the period March 2020-2022 and compare it with the activity during the period March 2019-2021. Objective: the aim of this study is to describe the clinical activity of the Breast Unit (BU) during the period March 2020-2022 and compare it with the activity during the period March 2019-2021. Method: retrospective observational study including patients attending the BU during the period March 2019-2022. Results: in the year before the pandemic, 30 new patients were assisted. Regarding the time between anatomopathological diagnosis and the initiation of the first treatment: in 73.3% of cases, it was ≤ 2 months, 16.6% > 2 months and ≤ 4 months, and in 10%, it was > 4 months. During the pandemic, 50 new patients were assisted, representing a decrease of approximately 16.6% in the number of new patients attended. Regarding the time between anatomopathological diagnosis and the initiation of the first treatment: in 41% of cases, it was ≤ 2 months, 33% > 2 months and ≤ 4 months, and in 25%, it was > 4 months. Conclusion: although the BU managed to maintain its clinical activity and continuity of most treatments during the COVID pandemic, there was a reduction in the number of patients referred to the service by approximately 16.6% and an increase in the time elapsed between diagnosis and the initiation of the first treatment.

Introdução: a crise sanitária causada pela COVID-19 impactou o atendimento de diversas patologias, inclusive o câncer. Para diminuir o risco de contrair SARS-CoV-2, reduziu-se o número de consultas, o que determinou um aumento da taxa de morbimortalidade por outras patologias, o que tem sido chamado de "segunda pandemia". Objetivo: descrever a atividade assistencial da Unidade de Mastologia (UM) no período março de 2020 - março de 2022 e compará-la com a do período março de 2019 - março de 2020. Material e método: estudo observacional retrospectivo que incluiu pacientes atendidos pelo CM no período março de 2019 - março de 2022. Resultados: no ano anterior à pandemia foram atendidos 30 novos pacientes. Em relação ao tempo entre o diagnóstico patológico e o primeiro tratamento: em 73,3% foi ≤2 meses, 16,6% >2 meses e ≤4 meses e em 10% foi >4 meses. Durante a pandemia, foram atendidos 50 novos pacientes, o que se traduz em uma queda de 16,6%no número de novos pacientes atendidos. Quanto ao tempo entre o diagnóstico patológico e o primeiro tratamento: em 41% foi ≤2 meses, 33% >2 meses e ≤4 meses e em 25% foi >4 meses. Conclusão: embora tenha conseguido manter a atividade assistencial e dar continuidade à maioria dos tratamentos, durante a pandemia de COVID-19 o número de pacientes encaminhados para o Serviço diminuiu cerca de 16,6% e houve um aumento do tempo decorrido entre o diagnóstico e o primeiro tratamento.

Menopausia quirúrgica en pacientes con mutación BRCA, el papel de la terapia hormonal / Surgical Menopause in Patients with BRCA Mutation, the Role of Hormone Therapy

Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

GATA Binding Protein 3 (GATA-3) expression evaluation as prognostic factor in breast cancer and its relationship with other immunemarkers

Introduction: Breast cancer is the most frequent cancer in which the mortality rate could be decreased by proper management. The GATA3 transcription factor is one of the most frequently mutated genes in breast cancer. Materials and Methods: We studied the immunohistochemical (IHC) expression of estrogen and progesterone receptor, human epidermal growth factor receptor 2, and GATA-3 in 166 radical/partial mastectomy specimens having different histologic grades and stages of breast carcinoma. All samples were obtained from the pathology department of Sina hospital in Tehran-Iran from 2010 to 2016. Results: There was a direct relationship between the luminal subtype carcinoma and higher GATA-3 expression (P-value: 0.001) and between triple-negative carcinoma and lower GATA-3 expression (P-value: 0.001). Moreover, there was a direct relationship between the metastasis rate and the tumor's grade with GATA-3 staining (P-value: 0.000 and 0.001, respectively). Conclusion: GATA-3 expression is related to the histopathologic and prognostic factors. GATA3 can be introduced as an important predictor in breast cancer patients.

Role of CD44 as cancer stem cell marker in triple-negative breast cancer and its association with histological grade and angiogenesis

Introduction: Cancer stem cells (CSC) within the tumors play a central role in tumorigenesis. It is, thus, of utmost importance to identify these cells to develop effective cancer therapy. Triple-Negative Breast Cancer (TNBC) is an aggressive molecular subtype of breast cancer associated with poor patient outcomes. The role of CD44 immunohistochemistry (IHC) as a putative CSC in breast carcinomas, particularly of the TNBC-subtype is ambiguous, with equivocal results. Aims and Objectives: The present study aims to assess the role of CSC in breast carcinoma by immunohistochemical analysis of CD44 expression in TNBC. The association of TNBC expressing CSC with histological grade as well as with angiogenesis (using CD34 IHC) has been studied. Materials and Methods: Biopsy samples from 58 patients with infiltrating ductal carcinoma, NST were studied. The histology of the tumor was sub-classified into grades 1–3. Based on immunohistochemical analysis (ER, PR, HER2/Neu), the cases were divided into TNBC and NTNBC groups. The tissue sections were also subjected to analysis for CD44 to identify the CSC-phenotype and CD34 to evaluate angiogenesis, to determine the microvascular density (MVD). Results: Out of the 58 cases in the study, 28 were TNBC and 30 were NTNBC. CSC phenotype (CD44 positive) was expressed significantly higher in the TNBC (78%) versus the NTNBC (53%) (p-value 0.043). The MVD estimated using CD34 IHC was lower in the TNBC group in our study, though the difference was not statistically significant. A larger proportion of cases in TNBC showed a higher histological grade (35%) in comparison to NTNBC (27%). However, statistically, it was not significant. Conclusion: Our study demonstrated that CD44 as a CSC marker is seen significantly more in the TNBC category of invasive ductal carcinomas. Further large-scale studies, to confirm these findings, will be of potential therapeutic and prognostic value.