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.

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.

Strategy and Status of Neoadjuvant Therapy for HER2-positive Breast Cancer / 肿瘤防治研究

Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.

Efficacy and safety of tyrosine kinase inhibitors in the treatment of HER2-positive breast cancer：a meta-analysis / 中国药房

OBJECTIVE To evaluate the efficacy and safety of tyrosine kinase inhibitors （TKI） in the treatment of HER2- positive breast cancer in order to provide evidence-based evidence for clinical medication. METHODS Retrieved from CNKI， Wanfang database， VIP， PubMed， Cochrane Library， Embase and Web of Science， randomized controlled trial （RCT） about TKI （trial group） versus drugs excluding TKI （control group） in the treatment of HER2-positive breast cancer were collected from the establishment of the database to April 2023. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4.1 and Stata 17 software. RESULTS Total of 24 RCT studies were included， involving 15 538 HER2-positive breast cancer patients. The meta- analysis results showed that compared with the control group， the progression-free survival （PFS） [HR＝0.91， 95%CI （0.80， 1.02）， P＝0.12]， overall survival （OS） [HR＝0.95， 95%CI （0.89， 1.01）， P＝0.11]， objective response rate （ORR） [OR＝1.21， 95%CI （0.86， 1.69）， P＝0.27]， and pathological complete response rate （pCR） [OR＝1.44， 95%CI （0.91， 2.27）， P＝0.12] had no statistically significant difference in the trial group； among the 3/4 grade ADRs， the trial group had a higher incidence of anemia [OR＝1.77， 95%CI （1.16，2.70）， P＝0.008]， rash [OR＝11.26， 95%CI （7.32，17.31）， P＜0.000 01]， paronychia [OR＝8.67， 95%CI（1.62，46.53）， P＝0.01]， diarrhea [OR＝10.17， 95%CI（5.03，20.58）， P＜0.000 01]， oral mucositis inflammation [OR＝ 9.34， 95%CI （3.13， 27.83）， P＜0.000 1]， elevated aspartate aminotransferase [OR＝2.09， 95%CI （1.13，3.84）， P＝0.02]， and hypokalemia [OR＝2.37， 95%CI （1.31，4.30）， P＝0.005] than that of the control group. Subgroup analysis results showed that compared with the placebo group， TKI could improve OS and ORR （P＜0.05）， while compared with trastuzumab， TKI had no advantage in PFS， OS， ORR， and pCR， and TKI combined with trastuzumab could significantly improve PFS， OS， ORR， and pCR compared with the trastuzumab group （P＜ 0.05）. Sensitivity analysis suggested that the results were relatively robust and the risk of publication bias was low. CONCLUSIONS Compared with trastuzumab， TKI has no advantages in PFS， OS， ORR and pCR in the treatment of HER2- positive breast cancer， but TKI combined with trastuzumab can significantly improve PFS， OS， ORR and pCR； TKI can increase the risk of grade 3/4 anemia， rash， paronychia， diarrhea， oral mucositis， elevated aspartate aminotransferase， and hypokalemia.

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.

Effects and mechanism of aucubin on malignant biological behavior of breast cancer cells / 中国药房

OBJECTIVE To investigate the effects of aucubin （Auc） on the malignant biological behavior of breast cancer cells by regulating cyclin-dependent kinase 1（CDK1）/cyclin B1（CCNB1）/Polo-like kinase 1 （PLK1） signaling pathway. METHODS Human breast cancer cells MCF-7 were divided into control group， Auc low-， medium- and high-concentration groups （AUC-L， AUC-M， AUC-H groups， 20， 40 and 80 μmol/L Auc）， Auc-H+pcDNA-NC group （80 μmol/L Auc+transfected pcDNA- NC plasmid）， and Auc-H+pcDNA-CDK1 group （80 μmol/L Auc+transfected pcDNA-CDK1 plasmid）. Cell proliferation， clonal formation， invasion and migration abilities， apoptosis and cycle distribution， and the expressions of related proteins of apoptosis， epithelial-mesenchymal transformation （EMT） and CDK1/CCNB1/PLK1 signaling pathway were detected in each group. The transplanted tumor model of BALB/c nude mice was established by subcutaneous inoculation of MCF-7 cell suspension， and the mice were divided into control group and Auc group （12 mice in each group）. The tumor volume， mass and the expressions of related proteins of CDK1/CCNB1/PLK1 signaling pathway in tumor tissues were detected. RESULTS Compared with control group， the number of clonal formation， proliferation rate， cell invasion number， scar healing rate， G1/G0 phase and S phase cell proportions， and the expressions of B cell lymphoma-2 （Bcl-2）， N-cadherin， fibronectin， CDK1， CCNB1 and PLK1 were decreased significantly （P＜0.05）. The apoptotic rate， G2/M phase cell proportion and the expressions of Bcl-2 associated X protein and E-cadherin were significantly increased， in a dose-dependent manner （P＜0.05）. Compared with the Auc-H+pcDNA-NC group， there was no statistical significance in the above indexes in the Auc-H group （P＞0.05）， while the above indexes in the Auc-H+ pcDNA-CDK1 group were significantly reversed （P＜0.05）. Compared with the control group， the tumor volume and mass， and the expressions of CDK1， CCNB1 and PLK1 in tumor tissue of Auc group were significantly decreased （P＜0.05）. CONCLUSIONS Auc can inhibit the proliferation， invasion and migration of breast cancer cells， induce cell cycle arrest， and inhibit the progression of EMT， which may be related to inhibiting the activation of the CDK1/CCNB1/PLK1 signaling pathway.

The characteristics of bone disseminated cells of 4T1 / 药学学报

Based on bone metastasis potential of mouse breast cancer 4T1 cells, the bone disseminated breast tumor cells 4T1 (B-4T1) were acquired through the screening of 6-mercaptopurine. The characteristics of B-4T1 were studied by morphological observation, proliferation assay, expression of epithelial and mesenchymal cell markers detection, transcriptome sequencing, and tumor formation experiments. The results showed that B-4T1 was round and spindle-shaped than primary 4T1 cells, and its proliferation rate was reduced, as well as epithelial cell adhesion molecule (EpCAM) and E-cadherin expression. The transcript level of N-cadherin was increased in the B-4T1, but not vimentin, indicating that B-4T1 had partial epithelial mesenchymal transition. Besides, B-4T1 had higher fatty acid metabolism and better tumor formation capacity. This study lays the experimental foundation for the basic study of metastasis in breast cancer. All animal experiments in this paper were conducted in accordance with the standards of the Animal Ethics Committee of China Pharmaceutical University.

Construction of a column-line graph for predicting the probability of survival in early-stage elderly HER2-positive breast cancer based on the SEER database / 中国临床药理学与治疗学

AIM: To construct column-line plots to predict survival in elderly patients with early-stage HER2-positive breast cancer using the Surveillance, Epidemiology and End Results (SEER) database. METHODS: 5 220 (based on the era of single-targeted therapy) and 1 176 (based on the era of dual-targeted therapy) patients screened in the SEER database were randomized into a training group and an internal validation group. COX proportional risk regression was used to screen survival-related predictors and build a column-line graphical model, and the accuracy and utility of the model were tested using the consistency index (C-index), calibration curves, and time-dependent ROC curves. Patients receiving chemotherapy and non-chemotherapy were statistically paired using two-group propensity score matching, and subgroup analyses were performed on the screened variables. RESULTS: The single-targeted therapy era line graph was constructed from seven variables: age, marital status, T-stage, N-stage, surgery, chemotherapy, and radiotherapy. The dual-targeted therapy era line graph was constructed from five variables: age, AJCC staging, surgery, chemotherapy, and radiotherapy. The results of the subgroup analysis showed that older HER2-positive breast cancer patients who received chemotherapy had better OS. CONCLUSION: Based on the SEER database, an accurate column-line graph predicting survival in elderly patients with early-stage HER2-positive breast cancer was established and validated. This study suggests that chemotherapy increases survival benefit in elderly patients.

Effect of quercetin's anti-breast cancer depending on presence of estrogen receptor via down-regulating long non-coding RNA MALAT-1 and its mechanism / 中国药理学通报

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

Down-regulation of METTL5 inhibits proliferation, migration and invasion of triple-negative breast cancer cells through Wnt/6-catenin signaling pathway / 中国药理学通报

Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

Clinical application and progression of monoclonal antibodies targeting HER2 extracellular domain Ⅳ in breast cancer / 中国药房

Human epidermal growth factor receptor 2 （HER2）-positive breast cancer is aggressive and prone to metastasis，and the applications of HER2 agents have improved the prognosis of patients with HER2-positive breast cancer. Among the marketed HER2 agents，macromolecular monoclonal antibodies that target the extracellular domain Ⅳ of HER2 were the cornerstone drugs of HER2-positive breast cancer，including trastuzumab，inetetamab，and margetuximab. Trastuzumab is available for the full-line treatment of breast cancer with sufficient proof of evidence-based medicine，sufficient practical experience and controllable safety. Inetetamab and trastuzumab have similar efficacy and controllable safety in HER2-positive metastatic breast cancer and neoadjuvant/ adjuvant therapy. Margetuximab focuses on patients carrying the CD16A-158F allele，and is an option of posterior line treatment for advanced breast cancer. It is necessary to select the most suitable drugs clinically according to the specific condition of the patient.

Characteristics of STAT Family Association with Breast Cancer and Intervention Effect of Traditional Chinese Medicine / 中国实验方剂学杂志

As the pace of society increases and lifestyles change， the incidence and mortality rates of breast cancer continue to rise. Targeted therapies are now promising in the treatment of breast cancer， and a variety of protein targets have been identified to play an important role in the development of breast cancer. Among them， signal transducer and activator of transcription （STAT） proteins constitute a crucial group that serves as important targets for transducing cellular transcriptional information， which can regulate downstream cell proliferation， apoptosis， cell migration， invasion， angiogenic factors， etc. and then affect the progression of breast cancer. The STAT family is closely associated with the inflammatory response to tumors and plays a landmark role in tumor development as well as in diagnosis and prognosis. The "inflammation-cancer" transformation refers to the process in which the inflammatory microenvironment caused by uncontrolled inflammation promotes normal cells to become cancerous. According to the theory of Chinese medicine， "heat toxicity" in "cancer toxicity" corresponds to inflammation， which is closely related to tumor development. As a major link associated with the inflammatory response， the STAT family has a promising role in the development and treatment of a variety of tumors， but its relevance to breast cancer remains inadequately explored. Chinese medicine has been shown to have good efficacy in the prevention and treatment of breast cancer， and some current studies have shown that the active ingredients and compounds of Chinese medicine have certain intervention effects on breast cancer-related STAT proteins， but there has not been a systematic review. In order to better sort out and summarize the studies on the effects of Chinese herbal medicines based on the STAT family interventions in breast cancer， this paper reviewed the studies on Chinese herbal medicines acting on the STAT family in recent years， aiming to provide new ideas for clinical applications in breast cancer and to provide thoughts for the development of STAT protein-based drugs.

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.

Particularités en imagerie du cancer du sein de la femme jeune de moins de 35 ans / Particularities of breast cancer imaging in young women under 35 years of age

Objectif: Le cancer du sein chez la femme jeune est rare etprésente des caractéristiques épidémiologiques, diagnostiques et pronostiques propres. L'objectif de notre étude est d'évaluerles caractéristiques radiologiques (mammographiques, échographiqueset par résonnancemagnétique IRM du cancer du sein chez la femme jeune Algérienne, de moins de 35 ans. Matériels etméthodes: Etude prospective, descriptiveau sein du service d'imagerie médicale du Centre Pierre et Marie Curie,d'Algerincluant 204patientes âgées de moins 35ans, étalée sur 3 ans allantentre janvier 2015et janvier 2017,chez lesquelles undiagnostic de cancer du sein a été porté,Elles ont toutes bénéficiésd'une mammographie numérique, d'une échographie et d'une IRM mammaireet d'unprélèvement percutané.Résultats:La fréquence du cancer du sein chez la femme jeune de moins de 35 ans était de 10,6%. L'âge moyen était de 30.9 ans. L'autopalpation d'un nodule était prédominante (87.2%). La densité mammaire était de type c et d dans 67.7%. Contrairement à l'idée établie, la mammographie avait permis souvent le diagnostic de ces tumeurs. A la mammographie, la répartition des cas selon le stade BI-RADS révèle que plus de la moitié (53.9%) était classée BI-RADS 5 ; 35.5 % des cas classés en BIRADS 4, 7.2% classés en BI-RADS 3 et un faible pourcentage (3.6 %) en BI-RADS 0. Pour l'échographie, la répartition des cas selon les stades BI-RADS révèle que plus de la moitié était classée ACR5, ce qui représente 64 %, 32.7 % classée en ACR4 et 3.3% en ACR3.A l'IRM, 71.1 % des cas ont été classés en ACR 5, 28.4% en ACR4 et 0.5 des cas en ACR 3. Le type histologique était de type carcinome canalaire infiltrant de grade III et II selon Scarff-Bloom et Richardson (SBR) dans 96.11% descas.Conclusion: L'expression radiologique est souvent non spécifique et évocatrice d'une lésion suspecte néanmoins nous avons constaté une plus grande fréquence de tumeurs d'allure bénigne en mammographie par rapport à l'échographie mammaire et à l'IRM mammaire. L'IRM mammaire reste donc utile dans la caractérisation lésionnelle et le bilan d'extension

Objective: Breast cancer in young women is rare and has its own epidemiological, diagnostic and prognostic features. The aim of our study was to evaluate the radiological (mammographic, ultrasonographic and MRI) characteristics of breast cancer iMaterials and methods: Prospective, descriptive study in the medical imaging department of the CPMC in Algiers, including 204 patients under 35 years of age, over a 3-year period from January 2017 to January 2020, diagnosed with breast cancer. They all underwent digital mammography, ultrasound and MRI of the breast and percutaneous sampling.Results: The incidence of breast cancer in young women under 35 was 10.6%. The mean age was 30.9 years. Autopalpation of a nodule was predominant (87.2%). Breast density was type c and d in 67.7%. Contrary to popular belief, these tumorswere often diagnosed by mammography. On mammography, the distribution of cases according to BIRADS stage revealed that over half (53.9%) were classified as BIRADS 5; 35.5% of cases classified as BIRADS 4, 7.2% classified as BIRADS 3 and a small percentage (3.6%) as BIRADS 0.On ultrasonography, the distribution of cases according to BIRADS staging revealed that over half were classified as ACR5, representing 64%, 32.7% as ACR4 and 3.3% as ACR3. On MRI, 71.1% of cases were classified as ACR 5, 28.4% as ACR4 and 0.5 of cases as ACR 3. Histological type was infiltrating ductal carcinoma grade III and II according to Scarff-Bloom and Richardson (SBR) in 96.11% of cases.Conclusion: Radiological expression is often non-specific and suggestive of a suspicious lesion. Nevertheless, we found a greater frequency of benign tumorsin mammography than in breast ultrasound and breast MRI. Breast MRI therefore remains useful for lesion characterization and extension assessmenn young Algerian women under 35 years of age.