Representações culturais do câncer de mama: uma revisão de escopo / Breast cancer cultural representations: a scoping review

Resumo O objetivo deste artigo é mapear a produção científica global sobre representações sociais ou culturais e câncer de mama no campo da saúde coletiva e discutir como esse fenômeno se apresenta na literatura. Foi realizada uma revisão de escopo, tendo como norte a seguinte pergunta: "Como representações culturais ou sociais no contexto do câncer de mama são descritas na produção científica global no âmbito da saúde coletiva?". As buscas foram realizadas em cinco fontes de literatura científica, sendo incluídos 45 estudos. O tratamento analítico seguiu a técnica de análise de conteúdo na modalidade temática. O acervo analisado pode ser tematizado nas seguintes categorias: (1) Comprometimento na imagem corporal e nas interações; (2) Espiritualidade; (3) Perda do controle da vida; (4) Seguir com a vida e (5) Associação a questões étnico-raciais. Apesar dos avanços da biomedicina, observa-se que nas representações do câncer de mama ainda permanecem metáforas associadas ao câncer no século passado. Conclui-se que, dentre outros aspectos, a atenção a mulheres com câncer de mama não pode ser pautada apenas pelas abordagens biomédica e epidemiológica, uma vez que essa doença é atravessada por saberes que competem com essas abordagens.

Abstract This article aims to map the global scientific production on social or cultural representations and breast cancer in Public Health and discuss how it is presented in the literature. We conducted a scoping review guided by the question: "How are cultural or social representations in the context of breast cancer described in the global scientific Public Health production?". We searched for works in five scientific literature sources and included 45 studies. The analytical process followed the content analysis technique in the thematic modality. The analyzed collection can be thematized into the following categories: (1) Compromised body image and interactions, (2) Spirituality, (3) Loss of control over life, (4) Going on with life, and (5) Association with ethnic-racial issues. Despite advances in biomedicine, we observed that representations of breast cancer still have metaphors associated with cancer in the last century. We conclude that, among other aspects, care for women with breast cancer cannot be guided only by biomedical and epidemiological approaches since this disease is traversed by knowledge that competes with these approaches.

Complicaciones por cirugía oncológica mamaria / Complications due to oncological breast surgery

RESUMEN Introducción: Cada año en América Latina, más de 200,000 mujeres son diagnosticadas con cáncer de mama. Como parte del tratamiento de esta enfermedad, la cirugía es uno de los pilares fundamentales. El acto quirúrgico es una experiencia extrema para el paciente y el cirujano, necesaria en esta patología para el tratamiento completo y, como todo acto médico, no está exento de complicaciones. En Paraguay no se cuentan con estadísticas sobre la prevalencia de las complicaciones debidas a cirugías por cáncer de mama, por lo que este trabajo tiene como principal objetivo establecer dicha frecuencia en un hospital de cuarto nivel de complejidad. Materiales y métodos: Estudio retrospectivo, observacional, de corte transversal. Muestreo no probabilístico de casos consecutivos. La selección de sujetos de estudios se realizó de la población de pacientes que fueron sometidos a cirugía por cáncer de mama, en el Hospital de Clínicas en el periodo enero de 2018 a agosto 2022, y que cumplan con los criterios de inclusión y exclusión. Todas las variables han sido extraídas de la ficha clínica y fueron documentadas en el formulario de registro de datos. Se esperaba una frecuencia de 42 % de complicaciones post quirúrgicas utilizando el programa estadístico EPIINFO 7 para un IC de 95% a precisión de 5%, el tamaño mínimo a incluir debía ser de 143 pacientes. Resultados: Se analizaron 203 historias clínicas de pacientes con diagnóstico de cáncer de mama que fueron sometidas a cirugía como parte del tratamiento, correspondientes al periodo comprendido entre enero de 2018 a agosto de 2022. Cumplieron con los criterios de inclusión 201 pacientes. Se registraron un total de 92 pacientes que presentaron alguna complicación relacionada a la cirugía, que corresponden 46 % del total de pacientes en el periodo de tiempo estudiado. De las complicaciones encontradas, 40 desarrollaron seromas, representando el 43% del total de pacientes con complicaciones; 18 pacientes tuvieron infección de la herida operatoria, representando el 20%. 7 pacientes presentaron dehiscencia de la herida operatoria, siendo el 7,5% del total; y 5 desarrollaron un hematoma, siendo el 5,3%. Entre otras complicaciones encontradas, 4 pacientes presentaron linfedema (4,3%), 4 dolor crónico (4,3%), 3 extrusión de prótesis mamaria (3,2 %), 2 de celulitis del miembro superior afecto (2,1%), 2 presentaron necrosis del complejo areola-pezón (2,1%), 1 sufrimiento de piel sin necrosis, 1 sufrimiento del complejo areola-pezón sin necrosis (1% ambos), 1 presentó fistula (1%), 1 disfunción del miembro superior homolateral (1%), y una contractura capsular (1%). Discusión: Se registraron 92 pacientes con una complicación post quirúrgica luego de una cirugía por cáncer de mama; representa así el 46% del total de pacientes estudiados. Esta prevalencia se corresponde con lo publicado en la literatura. En cuanto a las complicaciones encontradas, la más frecuente en nuestra revisión fue el seroma, que se presentó en un 40% de las complicaciones. Las publicaciones describen a esta como una de las complicaciones más frecuentemente relacionadas a la cirugía mamaria, con frecuencias que varían desde 18 al 86% según diversos autores. Conclusión: De 201 pacientes que cumplieron con los criterios de inclusión y exclusión, se registraron un total de 92 pacientes que presentaron alguna complicación relacionada a la cirugía, que corresponden 46 % del total de pacientes en el periodo de tiempo estudiado. La complicación más frecuente fue el seroma. Todos los hallazgos de este estudio se correlacionan con lo encontrado en la literatura.

Introduction: Every year in Latin America, more than 200,000 women are diagnosed with breast cancer. As part of the treatment of this disease, surgery is one of the fundamental pillars. The surgical act is an extreme experience for the patient and the surgeon, necessary in this pathology for complete treatment and, like any medical act, it is not exempt from complications. In Paraguay there are no statistics on the prevalence of complications due to surgeries for breast cancer, so the main objective of this work is to establish said frequency in a hospital of fourth level of complexity. Materials and methods: retrospective, observational, cross-sectional study. non-probabilistic sampling of consecutive cases. The selection of study subjects was made from the population of patients who underwent surgery for breast cancer, at the Hospital de Clínicas in the period January 2018 to August 2022, and who met the inclusion and exclusion criteria. All the variables have been extracted from the clinical record and were documented in the data recording form. A frequency of 42% of post-surgical complications was expected using the statistical program EPIINFO 7 for a CI of 95% with a precision of 5%, the minimum size to include had to be 143 patients. Results: 203 medical records of patients diagnosed with breast cancer who underwent surgery as part of the treatment, corresponding to the period from January 2018 to August 2022, were analyzed. 201 patients met the inclusion criteria. A total of 92 patients who presented some complication related to surgery were registered, corresponding to 46% of the total number of patients in the period of time studied. Of the complications found, 40 developed seromas, representing 43% of all patients with complications; 18 patients had surgical wound infection, representing 20%. 7 patients presented dehiscence of the surgical wound, being 7.5% of the total; and 5 developed a hematoma, being 5.3%. Among other complications found, 4 patients presented lymphedema (4.3%), 4 chronic pain (4.3%), 3 extrusion of breast prosthesis (3.2%), 2 cellulitis of the affected upper limb (2.1%), 2 presented necrosis of the nipple-areola complex (2.1%), 1 suffering from skin without necrosis, 1 suffering from the nipple-areola complex without necrosis (1% both), 1 presented fistula (1%), 1 homolateral upper limb dysfunction (1%), and capsular contracture (1%). Discussion: 92 patients with a post-surgical complication after surgery for breast cancer were registered; thus represents 46% of all patients studied. This prevalence corresponds to what has been published in the literature. Regarding the complications found, the most frequent in our review was seroma, which occurred in 40% of the complications. The publications describe this as one of the complications most frequently related to breast surgery, with frequencies ranging from 18 to 86% according to various authors. Conclusion: Of 201 patients who met the inclusion and exclusion criteria, a total of 92 patients who presented some complication related to surgery were registered, corresponding to 46% of the total number of patients in the period of time studied. The most frequent complication was seroma. All the findings of this study correlate with what is found in the literature.

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.

Algoritmo para la selección de colgajos perforantes perimamarios en reconstrucción inmediata poscirugía conservadora / Algorithm to select chest wall perforator flaps in immediate conservative breast surgery reconstruction

RESUMEN Antecedentes: los colgajos perforantes perimamarios son de gran utilidad en la reconstrucción mamaria inmediata en cirugía conservadora. Objetivo: describir los resultados del empleo de un algoritmo sobre colgajos perforantes perimamarios en la reconstrucción mamaria inmediata después de cirugía conservadora por cáncer de mama. Material y métodos: se llevó a cabo un estudio retrospectivo descriptivo. Se revisaron las historias clínicas de las pacientes operadas entre enero de 2020 y diciembre de 2022 por carcinoma de mama con cirugía conservadora y que requirieron reconstrucción con colgajos perimamarios. Las indicaciones incluyeron déficit de volumen, defecto de contorno y asimetría. Se evaluó el pedículo vascular del colgajo mediante Doppler color en todos los casos, lo que permitió seguir un algoritmo para la selección de la mejor opción de colgajo. Resultados: se realizaron 20 colgajos en 19 pacientes. Promedio de edad: 52 años ± 11 (rango 30-76). No existieron complicaciones intraoperatorias. Una paciente requirió reoperación por compresión del pedículo vascular del colgajo por hematoma, con la pérdida parcial, y otro colgajo sufrió epidermólisis superficial. No hubo pérdidas totales de ningún colgajo. Todas recibieron radioterapia posoperatoria y no experimentaron pérdida de volumen ni retracciones. Con un promedio de seguimiento de 15 meses, las pacientes valoraron los resultados a 6 meses como excelente en 7, bueno en 11 y regular en 2. Conclusión: la selección de colgajos perforantes locales para corregir defectos mamarios después de cirugía conservadora, mediante el examen con Doppler color preoperatorio para la identificación del pedículo vascular y un algoritmo específico, permitió obtener resultados estéticos satisfactorios sin requerir elementos aloplásticos ni revisiones posteriores.

ABSTRACT Background: Chest wall perforator flaps are a good option for immediate breast reconstruction after conservative surgery. Objective: The aim of this study was to describe the clinical results of an algorithm for using chest wall perforator flaps for breast reconstruction after breast-conserving surgery for breast cancer. Material and methods: We conducted a descriptive and retrospective study. The information was retrieved from the medical records of the patients diagnosed with breast cancer who underwent breast-conserving surgery and required reconstruction using chest wall perforator flaps between January 2020 and March 2022. The indications included volume deficit, contour defect and asymmetry. The vascular pedicle of the flap was evaluated by color Doppler ultrasound in all cases, which allowed us to follow an algorithm for selecting the best flap option. Results: Twenty flaps were made in 19 patients. Mean age: 52 years ± 11 (range 30-76). There were no intraoperative complications. One patient required reoperation due to a hematoma with compression of the vascular pedicle of the flap with partial flap loss, and another flap presented superficial epidermolysis. There were no cases of complete flap loss. All the patients underwent postoperative radiation therapy without loss of volume or retractions. Mean follow-up was 15 months. At 6 months, patients rated the results as excellent, good, and fair in 7, 11, and 2 cases, respectively. Conclusion: The selection of local perforator flaps to correct breast defects after conservative surgery, using preoperative color Doppler ultrasound to identify the vascular pedicle and a specific algorithm, allowed us to obtain satisfactory aesthetic results without the need for alloplastic elements or subsequent revisions.

ABCG2 polymorphism and rivaroxaban pharmacokinetics in healthy individuals after a single dose

Rivaroxaban is a direct factor Xa inhibitor. Its interindividual variability is large and may be connected to the occurrence of adverse drug reactions or drug inefficacy. Pharmacogenetics studies concentrating on the reasons underlying rivaroxaban's inadequate response could help explain the differences in treatment results and medication safety profiles. Against this background, this study evaluated whether polymorphisms in the gene encoding the ABCG2 transporter modify the pharmacokinetic characteristics of rivaroxaban. A total of 117 healthy volunteers participated in two bioequivalence experiments with a single oral dose of 20 mg rivaroxaban, with one group fasting and the other being fed. Ultra-high-performance liquid chromatography coupled with mass spectrometry was employed to determine the plasma concentrations of rivaroxaban, and the WinNonlin program was used to calculate the pharmacokinetics parameters. In the fasting group, the rivaroxaban pharmacokinetic parameters of Vd (508.27 vs 334.45 vs 275.59 L) and t1/2 (41.04 vs 16.43 vs 15.47 h) were significantly higher in ABCG2 421 A/A genotype carriers than in ABCG2 421 C/C and 421 C/A genotype carriers (P<0.05). The mean values of Cmax (145.81 vs 176.27 vs 190.19 ng/mL), AUC0-t (1193.81 vs 1374.69 vs 1570.77 ng/mL·h), and Cl (11.82 vs 14.50 vs 13.01 mL/h) for these groups were lower, but this difference was not statistically significant (P>0.05). These findings suggested that the ABCG2 421 A/A genotype may impact rivaroxaban parameters after a single dose in healthy subjects. This finding must be validated before it is applied in clinical practice.

PKMYT1 Promotes Epithelial-Mesenchymal Transition Process in Triple-Negative Breast Cancer by Activating Notch Signaling

ABSTRACT Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks receptors for targeted therapy. Deeper insight into the molecular mechanisms regulating TNBC metastasis is urgently needed. The epithelial-mesenchymal transition process facilitates the metastasis of neighboring epithelial tumor cells. Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, is upregulated in BC, and its high expression predicts poor prognosis in BC patients. Notch signaling activation is a pathognomonic feature of TNBC. PKMYT1 has been found to induce EMT in non-small cell lung cancer by activating Notch signaling. However, whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling remains unknown. Objectives: The objective of this study was to investigate whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling. Methods: Fifty cases of surgically resected BC samples (tumor and adjacent non-tumor tissue samples) were collected from patients diagnosed with BC. We measured the expression of PKMYT1 in clinical samples with real-time quantitative polymerase chain reaction (RT-qPCR). For in vitro analysis, RT-qPCR and Western blotting were conducted to evaluate PKMYT1 expression in TNBC cells. Then, the viability, migration, and invasion of TNBC cells were detected by cell counting kit-8 assays, wound healing assays, and Transwell assays. The EMT event was examined by evaluating the levels of EMT-associated proteins. For in vivo analysis, xenograft models in nude mice were established to explore PKMYT1 roles. E-cadherin and Ki67 expression in xenograft models were estimated by immunohistochemistry staining. Hematoxylin and eosin staining was performed to assess tumor metastasis. The underlying mechanisms by which PKMYT1 affected the malignant phenotypes of TNBC cells were explored by Western blotting measuring the pathway-associated proteins. Results: PKMYT1 was upregulated in BC tissues and cells, and its knockdown prevented cell proliferation, migration, invasion, and EMT event in TNBC. Mechanistically, Notch signaling was inactivated by PKMYT1 depletion, and Notch activation abolished the PKMYT1 silencing-induced inhibition in the malignant phenotypes of TNBC cells. For in vivo analysis, PKMYT1 knockdown inhibited tumorigenesis and metastasis of TNBC. Conclusion: PKMYT1 promotes EMT, proliferation, migration, and invasion of TNBC cells and facilitates tumor growth and metastasis by activating Notch signaling.

The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

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.

Brain Mechanisms of Chemotherapy-Related Cognitive Impairment in Breast Cancer Treated with Acupuncture：Based on Resting-State Functional Magnetic Resonance Imaging / 中医杂志

ObjectiveTo investigate the mechanism of acupuncture in the treatment of chemotherapy-related cognitive impairment （CRCI） of breast cancer based on resting-state functional magnetic resonance imaging （rs-fMRI）. MethodTwenty-five patients with CRCI of breast cancer were included and treated with the acupuncture based on the method of regulating qi and blood， nourishing mind and benefiting intelligence； the selected acupoints included Zusanli （ST 36， bilateral）， Xuehai （SP 10， bilateral）， Tanzhong （CV 17）， Zhongwan （CV 12）， Qihai （CV 6）， Baihui （GV 20）， Fengfu （GV 16， bilateral）， Xinshu （BL 15， bilateral）， Tongli （HT 5， bilateral）， Zhaohai （KI 6， bilateral）， Yixi （BL 45， bilateral） twice a week， each time interval of 2-3 days， for 8 weeks. The scores of Montreal Cognitive Assessment （MoCA）， Mini-mental State Examination （MMSE）， European Cancer Research and Treatment Organization Quality of Life Questionnaire （EORTC QLQ-C30） were compared before and after acupuncture， and the effectiveness were evaluated by MoCA scale. The patients received rs-fMRI before and after treatment， and used low-frequency oscillation amplitude and functional connectivity （FC） analysis to extract the mean zALFF values of regions of interest such as bilateral anterior cingulate gyrus， bilateral hippocampus， bilateral amygdala， bilateral temporal pole middle temporal gyrus， and bilateral temporal pole supramarginal gyrus for comparison， and used the brain regions with statistically significant differences in the pre- and post-treatment zALFF values as the seed points for the seed-point-based FC Analysis. Correlation analyses were performed between the imaging metrics and the clinical scales. ResultsTwenty-four patients with CRCI of breast cancer completed treatment and follow-up. The zALFF values of the left hippocampus， left amygdala， and left temporal pole temporal gyrus in patients' rs-fMRI decreased after treatment （P＜0.05 or P＜0.01）， and left temporal pole temporal gyrus and right posterior cerebellar lobe FC were elevated （t = -5.169）， and MoCA scale total scores and visuospatial and executive， naming， and delayed recall cognitive scores， MMSE scale total scores， and EORTC QLQ-C30 scale mood scores were significantly higher （P＜0.05 or P＜0.01）. The total effective rate of MoCA was 58.33%. The difference in zALFF values of the left temporal pole middle temporal gyrus before and after treatment was negatively correlated with the MoCA total score （r= -0.499， P = 0.015）， as well as the difference in abstract function （r = -0.498， P = 0.016）. ConclusionThe acupuncture method of regulating qi and blood， nourishing mind and benefiting intelligence can improve the cognitive function of breast cancer patients with CRCI， and its mechanism may be related to improving the functional activities of hippocampus， amygdala and temporal lobe， as well as the functional connections of left temporal pole-temporal middle gyrus and right posterior cerebellar lobe.

Advances in Endoscopic Techniques for Surgical Management of Breast Cancer： A Comprehensive Review / 中山大学学报(医学科学版)

With the improvement in quality of life and the development of medical science and technology， people's requirements for postoperative beauty are correspondingly improved. On the premise of ensuring safety and feasibility， the advantages of endoscopic small incisions are used to treat breast diseases. With the vigorous promotion of scholars all over the world， endoscopic treatment of breast cancer has changed from concept to reality. This article will briefly describe the development history of endoscopic treatment of breast cancer， introduce the indications obtained by experts from all over the world through practice， as well as the surgical methods of endoscopic treatment of breast cancer that have evolved based on traditional breast cancer surgery， and discuss the controversy and prospect of endoscopic treatment of breast cancer.

Correlation Analysis of Myelosuppression after Chemotherapy for Triple-Negative Breast Cancer and Its Prognosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether severe myelosuppression after chemotherapy is associated with prognosis in patients with breast cancer. MethodsTriple negative breast cancer （TNBC） patients who received chemotherapy at the Second Affiliated Hospital of Nanchang University from May 2， 2013 to May 2， 2018 were divided into a control group （no/mild myelosuppression） and a case group （severe myelosuppression）. In this study， 251 patients with TNBC met the inclusion and exclusion criteria， including 125 patients in the control group （20 patients with grade 0 myelosuppression， 43 patients with grade I myelosuppression， 62 patients with grade Ⅱ myelosuppression）， 126 patients in the case group （114 patients with grade Ⅲ myelosuppression， 12 patients with grade Ⅳ myelosuppression）. The general clinicopathological data of the patients in the two groups， including age， pathological type of tumor， tumor T stage， tumor N stage， tumor Nottingham grade， intravascular cancer thrombus， were analyzed using the χ2 test. The disease-free survival （DFS） and overall survival （OS） of the two groups were analyzed using the Kaplan-Meier method. A Cox proportional hazards regression model with multiple factors was used to analyze the impact of post-chemotherapy severe myelosuppression on disease-free survival （DFS） and overall survival （OS） in patients with TNBC. ResultsThe differences in general clinicopathologic data between the two groups of patients were not statistically significant （all P＞0.05）. The 5-year disease-free survival （DFS） rate was significantly lower in the control group compared with the case group （75.2% vs. 85.7%， P=0.027）. However， there was no statistically significant difference in the 5-year overall survival （OS） rate between the two groups （88.8% vs. 95.2%， P=0.057）. The analysis of the multifactorial Cox proportional hazards regression model revealed that post-chemotherapy severe myelosuppression was an independent protective factor for disease-free survival （DFS） （HR=0.332， 95% CI： 0.173-0.638， P=0.001） and overall survival （OS） （HR=0.193， 95% CI： 0.062-0.602， P=0.005） in TNBC patients. ConclusionOur results show that TNBC patients with severe myelosuppression after chemotherapy have longer disease-free survival （DFS） than those with no/mild myelosuppression， and overall survival （OS） also tend to be prolonged compared with those with no/mild myelosuppression， and severe myelosuppression after chemotherapy can be used as an independent predictor of a good prognosis in breast cancer.

Research on the role of resveratrol against breast cancer / 中国药房

Breast cancer （BC） ranks first in the incidence rate of female malignant tumor， the notable features of which include high invasive behavior， high malignant degree and poor prognosis. Resveratrol， a plant antioxidant， has been identified as a potential therapeutic agent for the occurrence and progress of BC. This article explores the mechanism of resveratrol intervention in BC by evaluating several in vitro and in vivo studies. It was found that resveratrol can weaken the proliferation and survival ability of BC cells， suppress their growth， metastasis， and invasion， and reverse their resistance to adriamycin by promoting cell apoptosis， regulating autophagy， inhibiting glycolysis and regulating the tumor microenvironment， expressions of matrix metalloproteinases， epithelial-mesenchymal transition and drug-resistant proteins， etc. The limited number of clinical trial studies on resveratrol， mainly focusing on prevention effect of it on breast cancer， may be one of the reasons that affect the comprehensive evaluation of the anti-cancer efficacy of resveratrol.

Research on the role of resveratrol against breast cancer / 中国药房

Breast cancer （BC） ranks first in the incidence rate of female malignant tumor， the notable features of which include high invasive behavior， high malignant degree and poor prognosis. Resveratrol， a plant antioxidant， has been identified as a potential therapeutic agent for the occurrence and progress of BC. This article explores the mechanism of resveratrol intervention in BC by evaluating several in vitro and in vivo studies. It was found that resveratrol can weaken the proliferation and survival ability of BC cells， suppress their growth， metastasis， and invasion， and reverse their resistance to adriamycin by promoting cell apoptosis， regulating autophagy， inhibiting glycolysis and regulating the tumor microenvironment， expressions of matrix metalloproteinases， epithelial-mesenchymal transition and drug-resistant proteins， etc. The limited number of clinical trial studies on resveratrol， mainly focusing on prevention effect of it on breast cancer， may be one of the reasons that affect the comprehensive evaluation of the anti-cancer efficacy of resveratrol.

miR-378a-3p Targets NUAK2 to Inhibit Proliferation, Migration, and Invasion of Breast Cancer Cells / 肿瘤防治研究

Objective To explore the mechanism of microRNA-378a-3p (miR-378a-3p) affecting the development of breast cancer (BC) cells. Methods The expression of miR-378a-3p in BC cells based on the Cancer Genome Atlas Program database was analyzed. The starBase, miRDB, and miRWalk databases were used to predict the target genes of miR-378a-3p. Double-luciferase reporter experiments were performed to verify the targeted regulation of miR-378a-3p on NUAK family kinase 2 (NUAK2). Real-time fluorescence quantitative PCR and Western blot analyses were used to detect the expression of miR-378a-3p and NUAK2 mRNA and protein in BC cells. Cell proliferation ability was detected through cell-proliferation experiments. Cell scratch assay and invasion assay were used to detect the migration and invasion abilities of cells, respectively. Apoptosis and cell-cycle experiments were conducted to detect cell apoptosis rate and cell cycle distribution. Results The expression of miR-378a-3p was significantly downregulated in BC cells, and miR-378a-3p overexpression inhibited the proliferation, migration, and invasion of BC cells. miR-378a-3p directly targeted NUAK2 and inhibited the mRNA and protein expression of NUAK2. Conclusion miR-378a-3p inhibits the proliferation, migration, and invasion of BC cells by targeting NUAK2.

Visualization Analysis of Research Hotspots of Breast Cancer Microenvironment Based on CiteSpace and VOSviewer / 肿瘤防治研究

Objective To explore the status of knowledge graph-based research into breast cancer microenvironment and to predict future research hotspots. Methods The literature related to breast cancer microenvironment in recent 20 years was retrieved from CNKI and Web of Science Core Collection database and analyzed with CiteSpace and VOSviewer. Results A total of 825 Chinese articles and 16,221 English articles were retrieved. Visual analysis showed that research focus has gradually shifted from cellular research to molecular research and drug innovation. Cancer stem cells, PD-1, PD-L1, immune checkpoint inhibitors, and nanoparticles are the main subjects of interest in research on breast cancer microenvironment, and the United States has the largest number of studies on breast cancer microenvironment, followed by China and Italy. Conclusion Current research mainly focuses on tumor stemness, immunotherapy, and nanodelivery. Owing to deepening research in this field, the targeting of the breast cancer microenvironment for the prevention of tumor development and metastasis and improvement of tumor prognosis has emerged as a new research direction.

Association between endometrial cancer and breast cancer: a bidirectional Mendelian randomization study / 预防医学

Objective@#To examine the causal relationship between endometrial cancer and breast cancer using bidirectional two-sample Mendelian randomization (MR) approach.@*Methods@#Genetic association data of endometrial cancer were collected through a meta analysis, including 54 884 participants and 9 464 330 single nucleotide polymorphisms (SNPs), and genetic association data of breast cancer were collected through the Breast Cancer Society Consortium, with 228 951 participants and 10 680 257 SNPs. A forward MR analysis was performed using the inverse variance weighted (IVW) method with 8 endometrial cancer-associated SNPs as instrumental variables and breast cancer as the study outcome, and a reverse MR analysis was performed with 112 breast cancer-associated SNPs as instrumental variables and endometrial cancer as the study outcome. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out.@*Results@#Forward MR analysis results showed that patients with genetically predicted endometrial cancer had an increased risk of breast cancer compared to those without endometrial cancer (OR=1.083, 95%CI: 1.037-1.132). Reverse MR analysis showed that patients with genetically predicted breast cancer had an increased risk of endometrial cancer compared to those without breast cancer (OR=1.070, 95%CI: 1.010-1.134). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results.@*Conclusion@#There are bidirectional causal relationship between endometrial cancer and breast cancer.

Effects of Lentivirus-Mediated CIB1 Silencing on Biological Behavior of Breast Cancer Cells / 肿瘤防治研究

Objective To investigate the effects of calcium and integrin-binding protein 1 (CIB1) on the cell proliferation, invasion, apoptosis, and migration of triple-negative breast cancer cells and its possible mechanism. Methods MDA-MB-231 and MDA-MB-468 cells were divided into CIB1-knockdown(infected with CRISPR/Cas9 lentivirus) and negative-control groups. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays were performed to detect cell proliferation. Cell apoptosis was determined through flow cytometry. Scratch and Transwell experiments were conducted to measure the migration and invasion abilities of cells. The mRNA and protein expression levels of β-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK-3β), and c-myc were detected via real-time quantitative polymerase chain reaction and Western blot. Results Compared with the negative-control group, the CIB1-knockdown group showed decreased cell proliferation, invasion, and migration (P<0.05) and increased cell apoptosis (P<0.05). The mRNA and protein expressions of β-catenin, APC, and c-myc decreased (P<0.05), and that of GSK-3β increased (P<0.05). Conclusion CIB1 knockdown can inhibit cell proliferation, invasion, and migration and promote the apoptosis of breast cancer cells. Its mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway.

Folic Acid-Modified Liposome Quercetin Induces Apoptosis of Triple-Negative Breast Cancer Cells via Mitochondrial Apoptosis Mediated by JAK2/STAT3 Signaling Pathway / 肿瘤防治研究

Objective To investigate the effect of folic acid–modified liposome quercetin (FLQ) on the proliferation and apoptosis of triple negative breast cancer (TNBC) cells and explore its underlying mechanism. Methods CCK-8 was used to detect the effect of FLQ on TNBC cell viability. Colony formation assay was conducted to detect the effect of FLQ on TNBC cell proliferation. Flow cytometry was performed to detect the effect of FLQ on TNBC cell apoptosis, the levels of intracellular ROS, and mitochondrial membrane potential. Western blot analysis was conducted to detect the expression levels of JAK2/STAT3 signaling pathway-related and apoptosis-related proteins. Results FLQ inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells (P=0.023, P<0.001). It promoted mitochondrial membrane potential collapse and increased the intracellular ROS levels of MDA-MB-231 cells (P=0.003, P=0.034); inhibited the phosphorylation levels of JAK2 and STAT3; upregulated the expression levels of the proapoptotic proteins Bax, Bak, cytochrome C, and Cleaved-Caspase-3 (P<0.001, P<0.001); and downregulated the expression levels of the antiapoptotic proteins Bcl2 and Bcl-xL (P=0.037, 0.028). Conclusion FLQ inhibits the proliferation and induces the apoptosis of MDA-MB-231 cells. These effects may be related to the activation of the mitochondrial apoptosis pathway through the inhibition of the JAK2/STAT3 signaling pathway.

Clinical Significance of FOXP3 Expression in BRCA1/2-Mutant Breast Cancer / 肿瘤防治研究

Objective To investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer. Methods A total of 48 BRCA mutation carriers (16 with BRCA1 and 32 with BRCA2) and 78 age-matched non-carriers were included in this study. Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues. The FOXP3 RNA expression in 39 BRCA1, 36 BRCA2, and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombination deficiency scores were evaluated to validate the immunohistochemistry results. Results The FOXP3 positive rate was 43.8% (7/16) in BRCA1 mutation carriers, 59.4% (19/32) in BRCA2 mutation carriers, and 9.0% (7/78) in non-carriers. The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers (P=0.002; P<0.001). TCGA-BRCA results showed that the FOXP3 RNA level in BRCA1/2 mutant breast cancer was significantly higher than that in non-carriers (P=0.02, P=0.004). The FOXP3 RNA level was positively correlated with the homologous recombination deficiency score (Spearman R=0.30, P<2.2e-16). Conclusion Patients with BRCA1/2 mutant breast cancers have higher FOXP3 expression than non-carriers, and may be more sensitive to immunotherapy.

Causal Association Between Omega-3 Fatty Acids and Risk of Breast Cancer: A Mendelian Randomization Study / 肿瘤防治研究

Objective To explore the causal relationship between Omega-3 fatty acids and the risk of breast cancer via Mendelian randomization analysis. Methods Analysis was conducted on data from genome-wide association studies (GWASs) on Omega-3 fatty acids and breast cancer. The selected instrumental variables (IVs) comprised genetic loci associated with Omega-3 fatty acids. Various Mendelian randomization analysis methods, including inverse-variance weighted (IVW) method, MR–Egger regression analysis, weighted median, simple models, and weighted models, were used to evaluate the causal relationship between Omega-3 fatty acids and the risk of breast cancer. Results A total of 47 single-nucleotide polymorphisms strongly associated with Omega-3 fatty acids were selected as IVs. The analysis methods, including IVW method, revealed no causal relationship between Omega-3 fatty acids and the risk of breast cancer (P>0.05). Analysis methods, such as MR-Egger regression analysis, did not detect significant gene-level pleiotropy (P=0.319), which indicates the high sensitivity and robustness of analysis results. Conclusion The findings of this study suggest the absence of a causal relationship between Omega-3 fatty acids and the risk of breast cancer.