Assessment of the safety and efficacy of combination chemotherapy and PD-1/PD-L1 inhibitor treatment of breast cancer: A meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#As the efficacy of programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors combined with chemotherapy in curing breast cancer is still controversial, this meta-analysis compares the efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy alone in the treatment of breast cancer, which provides guidance for the clinical treatment.@*METHODS@#Relevant studies published as of April 2022 in the various databases including EMBASE, PubMed, and Cochrane Library were selected. Randomized controlled trials (RCTs) in which control patients underwent chemotherapy alone and experimental group patients underwent combination chemotherapy and PD-1/PD-L1 inhibitor treatment were included in this investigation. Investigations without complete information, researches from which information could not be extracted, duplicate articles, animal studies, review articles, and systematic reviews were excluded. STATA 15.1 was employed for all statistical analyses.@*RESULTS@#In total, eight eligible studies were identified, revealing that combination chemotherapy and PD-1/PD-L1 inhibitor treatment was linked to significant increases in progression-free survival (PFS) relative to chemotherapy alone (hazard ratio [HR] = 0.83, 95% confidence interval [CI]: 0.70-0.99, P = 0.032) but not overall survival (HR = 0.92, 95% CI: 0.80-1.06, P = 0.273). Pooled adverse event rates were also increased within the group of combination treatment relative to the chemotherapy group (risk ratio [RR] = 1.08, 95% CI: 1.03-1.14, P = 0.002). Specifically, nausea rates were lesser within the group of combination treatment relative to the group of chemotherapy (RR = 0.48, 95% CI: 0.25-0.92, P = 0.026). Subgroup analyses indicated that the PFS of patients who underwent combination atezolizumab or pembrolizumab and chemotherapy treatment were substantially longer than those of patients who underwent chemotherapy alone (HR = 0.79, 95% CI: 0.69-0.89, P ≤0.001; HR = 0.79, 95% CI: 0.67-0.92, P = 0.002).@*CONCLUSIONS@#The pooled results suggest that combination chemotherapy and PD-1/PD-L1 inhibitor treatment approaches help prolong PFS in breast cancer patients, but have no statistically significant effect on overall survival (OS). Additionally, combination therapy can significantly improve complete response rate (CRR) compared with chemotherapy alone. However, combination therapy was associated with greater rates of adverse events.

A real-world study of the effects of endocrine therapy on liver function in breast cancer / 中华外科杂志

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

Development in the last 20 years of anti-HER2 targeted therapy for breast cancer / 中华外科杂志

Since trastuzumab was listed and approved for breast cancer in 2002, China has entered a new epoch of targeted therapy. Over the past 20 years, anti-human epidermal growth factor receptor 2 (HER2) targeted therapy for breast cancer in China has experienced the era of single-target, tyrosine kinase inhibitors, double-target and anti-HER2 plus antibody-drug conjugate. Advancement in the anti-HER2 targeted therapy is continuously changing the treatment mode of patients with HER2 positive status and even HER2 low expression, significantly improved their prognosis. In the past 20 years, Chinese scholars have participated in international clinical researches, completed a series of registration studies of imported drugs, developed new drugs with proprietary intellectual property rights, enriched the evidence of clinical research on HER2-targeted therapy, and formed a treatment system with both international standards and Chinese characteristics. In particular, the formulation of the Chinese Society of Clinical Oncology Breast Cancer Guidelines and the Chinese expert consensus on anti-HER2 targeted treatment in breast cancer are the concentrated embodiments of Chinese wisdom.

Chinese expert consensus of albumin-bound paclitaxel in the treatment of breast cancer / 中华肿瘤杂志

Breast cancer is the most common malignant tumor of women, which seriously threatens women's health. Albumin-bound paclitaxel is the basic chemotherapy drug for breast cancer treatment. We can promote reasonable clinical medication and improve patients' quality of life by standardizing chemotherapy plans, rationally optimizing treatment strategy and managing adverse reactions of albumin-bound paclitaxel. In order to standardize the clinical application of albumin-bound paclitaxel in breast cancer, Chinese Medical Doctor Association Oncologist Branch Breast Cancer Group and International Medical Exchange Branch of China Anti-Cancer Association consulted guidelines and the latest evidence-based evidences and formulated Chinese expert consensus of albumin-bound paclitaxel in the treatment of breast cancer to provide reference for clinical diagnosis and treatment of breast cancer. The consensus mainly introduces the clinical application strategies and evidence-based evidences of albumin-bound paclitaxel in advanced therapy, neoadjuvant therapy and adjuvant therapy of breast cancer. Among them, the regimens containing albumin-bound paclitaxel are the better recommended regimens for preoperative neoadjuvant and advanced rescue therapy of breast cancer. However, there is little evidence in adjuvant therapy, so it is recommended to use albumin-bound paclitaxel cautiously. We also invited breast cancer clinical experts to vote on some controversial issues, including but not limited to the usage and dosage of albumin-bound paclitaxel, combined medication and management of peripheral neuropathy, and formed consensus recommendations for the reference of breast cancer clinical workers.

Oenothein B inhibits proliferation and migration of breast cancer cells by regulating P53 / 中国中药杂志

The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.

Use of artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer

:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)

Hormone therapy in the treatment of breast cancer and main outcomes in sexuality

Hormone-dependent breast cancer has growth factors that respond positively to the hormones estrogen and progesterone. Thus, adjuvant endocrine therapy causes decreased or undetectable serum levels of these hormones. However, this treatment can have side effects that compromise the sexual health of patients, such as dyspareunia, vaginal dryness and decreased libido. In this scenario, the objective of this work was to document the main outcomes in sexuality in women after treatment for hormonepositive breast cancer. Thus, this is an integrative literature review, in which the following databases were used: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS and Scientific Electronic Library Online (SCIELO), using the descriptors: "sexuality", "antineoplastic agents, hormonal" and "breast neoplasms", joined by the Boolean operator "AND". Full articles published in the last 5 years (2017-2022) were included; written in Portuguese or English. Articles dealing with non-hormone-dependent or metastatic breast cancer, or with patients younger than 18 years, or articles that did not answer the research question were excluded. In total, 26 articles were identified, of which 7 comprised the final sample of this review. A total of 3,850 women participated in the included studies. The main sexual dysfunctions found were: dyspareunia, hot flashes, decreased libido, vaginal dryness, breast tenderness, self-image concerns and hair loss. The symptom vaginal dryness was the most prevalent, mentioned in 71.4% of the articles included. In view of the adverse effects listed in this review, there is a need to carry out more studies on this topic, since the diagnosis of this comorbidity brings clinical, psychological, emotional, sociocultural and economic outcomes for the patient. Thus, a multidisciplinary team must assertively address these complaints to improve the overall quality of life of these women (AU)

Supervivencia de pacientes con cáncer de mama y cirugía conservadora / Survival in Patients with Breast Cancer and Conservative Surgery

Introducción: En la actualidad la cirugía conservadora, más que una opción en el tratamiento quirúrgico del cáncer de mama, es la técnica quirúrgica de elección. Objetivo: Caracterizar la supervivencia de los pacientes con cáncer de mama operados con cirugía conservadora. Métodos: Se realizó un estudio multicéntrico, retrospectivo descriptivo de corte longitudinal, en el Hospital Universitario Clínico Quirúrgico "Arnaldo Milián Castro" y el oncológico "Celestino Hernández Robau", ambos de la ciudad de Santa Clara provincia Villa Clara, en el período comprendido desde enero del 2011 hasta diciembre del 2020. Resultados: La supervivencia global de los pacientes con cáncer de mama y cirugía conservadora en aquellos que presentaron eventos (fallecidos) fue mayor en los portadores de carcinoma ductal infiltrante con 9,3 años. En el caso del estadio tumoral predominó la supervivencia en aquellos pacientes que estaban en estadios Ia y IIa con 9,8 y 9,1 años, respectivamente. Según la inmunohistoquímica, el subtipo molecular con mejor supervivencia global fue el Luminal B con 9,2 años. En cuanto al tratamiento definitivo aplicado presentaron mayor supervivencia global aquellos pacientes que recibieron esquemas de quimioterapia+ radioterapia+ hormono terapia y quimioterapia+ radioterapia con 9,4 y 8,8 años, respectivamente. Conclusiones: Existe una mayor supervivencia global en aquellos pacientes con carcinoma ductal infiltrantes (NOS), estadios tumorales Ia y IIa, con subtipo molecular Luminal B según inmunohistoquímica y con tratamientos definitivos de quimioterapia+ radioterapia+ hormonoterapia(AU)

Introduction: Nowadays, conservative surgery, rather than an option for the surgical treatment of breast cancer, is the surgical technique of choice. Objective: To characterize the survival of patients with breast cancer operated on with conservative surgery. Methods: A multicenter, retrospective, descriptive and longitudinal study was carried out at Hospital Universitario Clínico Quirúrgico "Arnaldo Milián Castro" and "Celestino Hernández Robau" oncologic hospital, both in the city of Santa Clara, Villa Clara Province, in the period from January 2011 to December 2020. Results: The overall survival of patients with breast cancer and conservative surgery in those who presented events (died) was higher in those with infiltrating ductal carcinoma, accounting for 9.3 years. In the case of tumor stage, survival was predominant in those patients with stages IA and IIA, accounting for 9.8 and 9.1 years, respectively. Concerning immunohistochemistry, the molecular subtype with the best overall survival was Luminal B, accounting for 9.2 years. Regarding the applied definitive treatment, those patients who received chemotherapy-radiotherapy-hormone therapy and chemotherapy-radiotherapy schemes presented better overall survival, accounting for 9.4 and 8.8 years, respectively. Conclusions: Overall survival is higher in patients with infiltrating ductal carcinoma (not otherwise specified), tumor stages IA and IIA, molecular subtype Luminal B according to immunohistochemistry, and definitive treatments with chemotherapy, radiotherapy, hormone therapy scheme(AU)

Efeitos adversos locorregionais da terapêutica oncológica em mulheres com câncer de mama avançado: revisão integrativa / Efectos adversos locorregionales de la terapia oncológica en mujeres con cáncer de mama avanzado: una revisión integradora / Locoregional adverse effects of cancer therapy in women with advanced breast cancer: an integrative review

RESUMO Objetivo: identificar os efeitos adversos locorregionais da administração da terapêutica oncológica endovenosa em mulheres com câncer de mama avançado. Metodo: revisão integrativa da literatura, que utilizou as bases de dados PubMed/MEDLINE, CINAHL, LILACS e EMBASE, sem recorte temporal, além de busca reversa dos artigos selecionados, atualizada até maio de 2022 A população contemplou mulheres com câncer de mama avançado submetidas à intervenção com terapêutica oncológica endovenosa com quimioterapia ou hormonioterapia ou anticorpo monoclonal, e o desfecho avaliou efeitos adversos locorregionais Resultados: identificaram-se 2.789 estudos, e a amostra final foi composta por 8 ensaios clínicos e 1 estudo observacional retrospectivo, sendo todos estudos internacionais e publicados no período de 1986 a 2018. Predominantemente, as pacientes tinham câncer de mama em estádio IV, idade de 50 anos ou mais e múltiplas metástases. Os efeitos adversos locorregionais foram: flebite, ulceração e/ou necrose, dor, eritema e reação no local da injeção não especificada. Os estudos não trazem detalhamento do tipo de cateter venoso, osmolaridade dos fármacos e cuidados preventivos para diminuição desses efeitos adversos. Conclusão: as evidências desses artigos mostraram que os efeitos adversos locorregionais estão presentes em estudos de eficácia dos fármacos oncológicos em mulheres com câncer de mama avançado. No entanto, destaca-se que a segurança da administração dos fármacos oncológicos não se apresenta elucidada nessa revisão, indicando necessidade de estudos de acompanhamento dos efeitos adversos.

RESUMEN Objetivo: identificación de los efectos adversos locorregionales de la administración de la terapia oncológica intravenosa en mujeres con cáncer de mama avanzado. Método: revisión bibliográfica integradora, que utilizó las bases de datos PubMed/MEDLINE, CINAHL, LILACS y EMBASE, sin corte de tiempo, además de una búsqueda inversa de los artículos seleccionados, actualizada hasta mayo de 2022 La población incluyó mujeres con cáncer de mama avanzado, sometidas a intervención con terapia oncológica endovenosa con quimioterapia u hormonoterapia o anticuerpo monoclonal y el resultado evaluó los efectos adversos locorregionales Resultados: se identificaron 2.789 estudios y la muestra final se compuso de ocho ensayos clínicos, un estudio observacional retrospectivo, todos estudios internacionales, publicados desde 1986 hasta 2018. Predominantemente, las pacientes tenían cáncer de mama en estadio IV, edad de 50 años o más y metástasis múltiples. Los efectos adversos locorregionales fueron flebitis, ulceración y/o necrosis, dolor, eritema y reacción en el lugar de la inyección no especificada. Los estudios no detallan el tipo de catéter venoso, la osmolaridad de los fármacos y los cuidados preventivos para reducir estos efectos adversos. Conclusión: las pruebas de estos artículos mostraron que los efectos adversos locorregionales están presentes en los estudios de eficacia de los fármacos oncológicos en mujeres con cáncer de mama avanzado. Sin embargo, cabe destacar que la seguridad de la administración de los fármacos contra el cáncer no se dilucida en esta revisión, lo que indica la necesidad de realizar estudios de seguimiento sobre los efectos adversos.

ABSTRACT Objective: to identify the locoregional adverse effects of administering intravenous oncologic therapy in women with advanced breast cancer. Method: this was an integrative literature review using the PubMed/MEDLINE, CINAHL, LILACS, and EMBASE databases, without a time cut, in addition to a reverse search of the selected articles updated until May 2022. The population included women with advanced breast cancer undergoing intervention with intravenous oncologic therapy with chemotherapy, hormone therapy, or monoclonal antibody, and the outcome assessed locoregional adverse effects. Results: 2,789 studies were identified, and the final sample consisted of 8 clinical trials and 1 retrospective observational study, all of which were international studies published from 1986 to 2018. Predominantly, patients with stage IV breast cancer, were aged 50 years or older, and had multiple metastases. Locoregional adverse effects were phlebitis, ulceration and/or necrosis, pain, erythema, and unspecified injection site reaction. The studies did not detail the type of venous catheter, the osmolarity of the drugs, and preventive care to reduce these adverse effects. Conclusion: the evidence from these articles showed that locoregional adverse effects are present in efficacy research of oncologic drugs in women with advanced breast cancer. Nonetheless, the safety of administering cancer drugs is not elucidated in this review, indicating the need for follow-up studies of adverse effects.

Nipple-sparing Mastectomy with Immediate Implant-based Reconstruction for Patients with Pure Ductal Carcinoma in Situ / Mastectomia preservadora demamilo com reconstrução imediata baseada em implante para pacientes com carcinoma ductal puro in situ

Abstract Objective The presence of an extensive intraductal component is associated to an increasing risk of relapse in the nipple-areola complex. The aim of the present study was to evaluate the outcomes of patients diagnosed with ductal carcinoma in situ (DCIS) who underwent nipple-sparing mastectomy (NSM) with immediate breast reconstruction using silicone implants. Methods We retrospectively analyzed the postoperative complications and oncological safety of 67 breast cancer patients diagnosed with pure DCIS who underwent NSM with immediate breast reconstruction using silicone implants between 2004 and 2018. Results Among the 127 NSM procedures performed, 2 hematomas (1.5%) and 1 partial nipple necrosis (0.7%) were observed. After a mean follow-up of 60months, the local recurrence rate was of 8.9%, the disease-free survival rate was of 90%, and 1 of the patients died. Conclusion Despite the local recurrence rate, we showed that NSM with immediate breast reconstruction using silicone implants is a feasible surgical approach, with a low rate of complications and high survival rates for patients with a diagnosis of pure DCIS when breast-conserving surgery is not an option.

Resumo Objetivo A presença de componente intraductal extenso é associada ao risco aumentado de recorrência no complexo aréolo-mamilar. O objetivo deste estudo foi avaliar os resultados de pacientes diagnosticados com carcinoma ductal in situ (CDIS)submetidas a adenomastectomia (nipple-sparing mastectomy, NSM, em inglês) com reconstrução mamária imediata utilizando prótese de silicone. Métodos Restrospectivamente, foramanalisadas as complicações pós-operatórias e a segurança oncológica de 67 pacientes com câncer de mama diagnosticadas com CDIS puro, e submetidas a NSM com reconstrução mamária imediata utilizando prótese de silicone, entre 2004 e 2018. Resultados Entre os 127 procedimentos realizados, 2 hematomas (1,5%) e 1 necrose parcial de mamilo (0,7%) foram observados. Após um período médio de 60 meses de seguimento, a taxa de recorrência local foi de 8,9%, a sobrevida livre de doença, de 90%, e apenas 1 paciente foi a óbito. Conclusão Apesar da taxa de recorrência local, demostrou-se que NSM com reconstrução mamária imediata comprótese de silicone é umprocedimento viável, combaixa taxa de complicação e alta sobrevida para pacientes com diagnóstico de CDIS puro quando a cirurgia conservadora da mama não é uma opção.

Anestesia total intravenosa en la cirugía oncológica de mama / Total intravenous anesthesia in oncologist breast surgery

Introducción: El cáncer es la principal causa de muerte. Cada año se diagnostican millones de mujeres con cáncer de mama que necesitan tratamiento quirúrgico, para lo cual la anestesia total intravenosa parece ser una excelente opción. Objetivo: Describir los resultados de la aplicación de la anestesia total intravenosa en las pacientes a las que se les efectuó cirugía oncológica de mama. Métodos: Se realizó un estudio observacional, descriptivo, longitudinal, prospectivo, en el Servicio de Anestesiología del Hospital General Docente "Abel Santamaría Cuadrado" en el período comprendido entre enero de 2013 y enero de 2015. Se estudió una población accesible de 111 pacientes seleccionados mediante criterios de inclusión y exclusión. Para el análisis estadístico se utilizaron distribuciones de frecuencias, cálculo de medidas de tendencia central y de dispersión. Algunas de las variables fueron tensión arterial, frecuencia cardíaca, saturación de oxígeno, complicaciones, tiempo de recuperación, nivel de sedación, respuesta analgésica. Resultados: Se logró gran estabilidad hemodinámica en más del 95 por ciento de las pacientes. Se detectó superficialidad anestésica en 1,80 por ciento de los casos. El 92,80 por ciento de los casos se recuperaron entre 10 y 20 min. Se presentó sedación adecuada en 106 pacientes. Las principales complicaciones fueron las náuseas y los vómitos en 9,01 por ciento. Existió una adecuada respuesta analgésica en 93,69 por ciento de los casos. Conclusiones: La aplicación de la anestesia total intravenosa para cirugía oncológica de mama arrojó resultados muy satisfactorios como método anestésico(AU)

Introduction: Cancer is the leading cause of death worldwide. Every year millions of women are diagnosed with breast cancer and they need surgical treatment, for which total intravenous anesthesia seems to be an excellent option. Objective: Describe the results of the application of total intravenous anesthesia in patients undergoing oncological breast surgery. Methods: An observational, descriptive, longitudinal, prospective study was conducted in the Anesthesiology Service of "Abel Santamaría Cuadrado" Hospital in the period between January 2013 and January 2015. An accessible population of 111 patients selected using inclusion and exclusion criteria was studied. For the statistical analysis, frequency distributions, calculation of measures of central tendency and dispersion were used. Some of the variables were blood pressure, heart rate, oxygen saturation, complications, recovery time, level of sedation, analgesic response. Results: High hemodynamic stability was achieved in more than 95 percent of the patients. Anesthetic superficiality was detected in 1.80 percent of cases. 92.80 percent of the cases recovered after 10 to 20 minutes. Adequate sedation was present in 106 patients. The main complications were nausea and vomiting in 9.01 percent There was an adequate analgesic response in 93.69 percent of the cases. Conclusions: The application of total intravenous anesthesia for oncological breast surgery yielded very satisfactory results as an anesthetic method(AU)

Subclinical Systolic Dysfunction during Chemotherapy for Breast Cancer

Abstract Background Cardiotoxicity is the main complication related to cancer therapy. Studies indicate that global longitudinal strain is an early detector of subclinical dysfunction of the left ventricle, preceding the decline in ejection fraction (EF). However, the reproducibility of such methodology has not been tested outside specialized centers. Objectives To assess the frequency of subclinical cardiotoxicity and to compare global longitudinal strain and EF measurements during the clinical course of patients undergoing chemotherapy for breast cancer. Methods This was an observational prospective study of 78 adult women who underwent serial echocardiograms (baseline and 1, 3, and 6 months after the beginning of chemotherapy), to evaluate biplane and 3D EF and global longitudinal strain. Cardiotoxicity and subclinical dysfunction were defined according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. Statistical significance was set at p < 0.05. Results The mean age of the patients was 50.1 ± 11.48 years. The frequency of subclinical cardiotoxicity (defined by global longitudinal strain) was 14.9% after 30 days of chemotherapy, 16.7% after 3 months, and 19.7% after 6 months, compared to 4.5%, 3%, and 6.6%, respectively, when clinical cardiotoxicity was determined according to EF. The group that developed subclinical cardiotoxicity by 30 days (group A) had a higher frequency of clinical cardiotoxicity at 3 months (p=0.028) and a lower mean biplane EF after 30 days (p= 0.036) than the group that showed no evidence of subclinical cardiotoxicity (group B). Conclusion Subclinical cardiotoxicity was frequent and began early, being associated with a drop in EF during the clinical course.

An injectable hydrogel/staple fiber composite for sustained release of CA4P and doxorubicin for combined chemotherapy of xenografted breast tumor in mice / 南方医科大学学报

OBJECTIVE@#To prepare an injectable hydrogel/staple fiber composite loaded with combretastain A-4 disodium phosphate (CA4P) and doxorubicin (DOX) and evaluate its antitumor efficacy via intratumoral injection.@*METHODS@#DOX-loaded PELA staple fibers (FDOX) were prepared using electro-spinning and cryo-cutting, and the drug distribution on the surface of the fibers was observed using a fluorescence microscope, and the encapsulation efficiency and loading capacity of FDOX were determined with a fluorospectro photometer. The fibers were then dispersed in CA4P-loaded PLGA-PEG-PLGA tri-block polymer solution at room temperature to obtain the hydrogel/staple fiber composite (GCA4P/FDOX). The thermo-sensitivity of this composite was determined by a test tube inverting method. An ultraviolet spectrophotometer and a fluorospectrophotometer were used to detect the release profile of CA4P and DOX, respectively. We observed in vivo gel formation of the composite after subcutaneous injection in mice. The in vitro cytotoxicity of GCA4P/FDOX composite in MCF-7 and 4T1 cells was assessed using cell Counting Kit-8 (CCK-8) reagent. In a mouse model bearing breast tumor 4T1 cell xenograft, we evaluated the antitumor efficacy of the composite by monitoring tumor growth within 30 days after intratumoral injection of the composite. HE staining, immunohistochemistry for Ki67 and immunofluorescence (TUNEL) assay were used for pathological examination of the tumor tissues 21 days after the treatments.@*RESULTS@#The average length of FDOX was 4.0±1.3 μm, and its drug loading capacity was (2.69±0.35)% with an encapsulation efficiency of (89.70±0.12)%. DOX was well distributed on the surface of the fibers. When the temperature increased to 37 ℃, the composite rapidly solidified to form a gel in vitro. Drug release behavior test showed that CA4P was completely released from the composite in 5 days and 87% of DOX was released in 30 days. After subcutaneous injection, the composite solidified rapidly without degradation at 24 h after injection. After incubation with GCA4P/FDOX for 72 h, only 30.6% of MCF-7 cells and 28.9% of 4T1 cells were viable. In the tumor-bearing mice, the tumor volume was 771.9±76.9 mm3 in GCA4P/FDOX treatment group at 30 days. Pathological examination revealed obvious necrosis of the tumor tissues and tumor cell apoptosis induced by intratumoral injection of G4A4P/FDOX.@*CONCLUSION@#As an efficient dual drug delivery system, this hydrogel/staple fiber composite provides a new strategy for local combined chemotherapy of solid tumors.

A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system Xc-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.

Religiosidade e Esperança no Enfrentamento do Câncer de Mama: Mulheres em Quimioterapia / Religiosity and Hope in Coping with Breast Cancer: Women in Chemotherapy / Religiosidad y Esperanza en el Cáncer de Mama: Mujeres en Quimioterapia

Introdução: O câncer de mama tem-se destacado como a neoplasia de maior incidência na Região Sudeste do Brasil. Na quimioterapia, que é a modalidade terapêutica mais utilizada para essa doença, os pacientes oncológicos podem apresentar diversas reações, assim, na tentativa de minimizar esses efeitos, buscam por estratégias não farmacológicas. Destacam-se duas estratégias de enfrentamento, a esperança e a religiosidade, as quais têm promovido resultados positivos e benéficos para pacientes em tratamento oncológico. Objetivo: Avaliar os níveis de religiosidade e esperança e analisar as relações presentes em mulheres com câncer de mama submetidas à quimioterapia. Método: Pesquisa quantitativa, com a aplicação de questionário sociodemográfico, da escala de esperança de Herth (EEH) e da escala de religiosidade da Universidade Duke (DUREL). Resultados: Participaram desta pesquisa 41 mulheres, com idade média de 53,61±11,8 anos. O escore mediano obtido na EEH foi de 39 (±9) e a variação foi de 32 a 48 pontos. O escore mediano da religiosidade organizacional foi de 5 (±2) e a variação obtida de 1 a 6 pontos. O escore mediano da religiosidade intrínseca foi de 15 (±1) e a variação obtida de 9 a 15 pontos. Na amostra da pesquisa, podem-se identificar o alto escore e a homogeneidade nas respostas. Conclusão: A esperança e a religiosidade de pacientes com câncer de mama não apresentaram correlação positiva entre si. No entanto, foram encontrados altos níveis de esperança e de religiosidade nas pacientes entrevistadas, o que demonstra a busca por terapêuticas não farmacológicas para o enfrentamento da doença

Introduction: Breast cancer stands out as the highest incident cancer in Brazil's Southeastern region. Cancer patients in chemotherapy, the most common therapeutic modality for this disease, have several reactions and to minimize these effects, they seek for non-pharmacological strategies. Hope and religiosity are two coping strategies often utilized because they have been promoting positive and beneficial results for patients undergoing cancer treatment. Objective: To assess the levels of religiosity and hope and analyze the current relationships of women with breast cancer submitted to chemotherapy. Method: Quantitative research, with the application of a sociodemographic questionnaire, the Herth hope scale (HHS) and the Duke University religion index (DUREL). Results: 41 women participated of this study, with mean age of 53.61±11.8 years. The median score obtained in the HHS was 39 (±9) and the variation was from 32 to 48 points. The median score of organizational religiosity was 5 (±2) and the variation obtained was 1 to 6 points. The median intrinsic religiosity score was 15 (±1) and the variation obtained was 9 to 15 points. In the study sample, it is possible to identify high score and homogeneity of the responses. Conclusion: Hope and religiosity of patients with breast cancer did not show a positive correlation. However, high levels of hope and religiosity were found in the patients interviewed, which demonstrates the search for non-pharmacological therapies to cope with the disease

Introducción: El cáncer de mama se ha destacado como la neoplasia con mayor incidencia en la Región Sudeste de Brasil. En la quimioterapia, que es la modalidad terapéutica más utilizada para esta enfermedad, los pacientes con cáncer pueden presentar varias reacciones, por lo que en un intento por minimizar estos efectos, buscan estrategias no farmacológicas. Destacan dos estrategias de afrontamiento, la esperanza y la religiosidad, que han promovido resultados positivos y beneficiosos para los pacientes sometidos a tratamiento oncológico. Objetivo: Evaluar los niveles de religiosidad y esperanza y analizar las relaciones actuales, en mujeres con cáncer de mama sometidas a quimioterapia. Método: Investigación cuantitativa, con la aplicación de un cuestionario sociodemográfico, la escala de esperanza de Herth (HHS) y la escala de religiosidad de la Universidad Duke (DUREL). Resultados: En esta investigación participaron 41 mujeres, con una edad media de 53,61±11,8 años. La mediana de la puntuación obtenida en la EHSS fue de 39 (±9) y el rango fue de 32 a 48 puntos. La puntuación media de la Religiosidad Organizativa fue de 5 (±2) y la variación obtenida fue de 1 a 6 puntos. La puntuación media de la Religiosidad Intrínseca fue de 15 (±1) y la variación obtenida fue de 9 a 15 puntos. En la muestra de la investigación se puede identificar una alta puntuación y homogeneidad en las respuestas. Conclusión: La esperanza y la religiosidad de las pacientes con cáncer de mama no mostraron una correlación positiva entre ellas. Sin embargo, se encontraron altos niveles de esperanza y religiosidad en los pacientes entrevistados, lo que demuestra la búsqueda de terapias no farmacológicas para afrontar la enfermedad

Clinical-Epidemiological Profile and Health-Related Quality of Life of Women with Breast Cancer During Chemotherapy Treatment: Observational Study / Perfil Clínico-Epidemiológico e Qualidade de Vida Relacionada à Saúde de Mulheres com Câncer de Mama durante Tratamento Quimioterápico: Estudo Observacionall / Perfil Clínico-Epidemiológico y Calidad de Vida Relacionada con la Salud de Mujeres con Cáncer de Mama en Tratamiento Quimioterápico: Estudio Observaciona

Introduction: Breast cancer may affect different profiles of women worldwide. In addition, chemotherapy to treat breast neoplasms directly affects health-related quality of life. Objective: To describe the clinical-epidemiological profile and to compare the general and specific health-related quality of life of women with breast cancer during chemotherapy. Method: In an observational and prospective study, 140 women with breast cancer in northeastern Brazil were evaluated in the intermediate cycle and at the end of chemotherapy. Quality of life was assessed using a general instrument (EORTC-QLQ-C30) and a specific module (EORTC-QLQ-BR23). Data were compared with a paired non-parametric test, with a significance level of 5%. Results: Regarding the clinical-epidemiological profile, the median age was 50 years, 82.9% were black or mixed-race, and 95% lived in Sergipe, Brazil. In addition, 50.7% had no occupation, the median family income was one minimum wage, as well as the median of education was eight years of study and only 40.7% have completed high school. Considering the data from the C30 and BR23 questionnaires, it was observed that most items and scales worsened at the end of chemotherapy when compared to the intermediate cycle. Among the items and scales with significant differences, most had moderate or high effect sizes. Conclusion: It is possible to conclude that the clinical-epidemiological profile was unfavorable and chemotherapy reduced several aspects of the health-related quality of life of women with breast cancer

Introdução: O câncer de mama pode acometer diferentes perfis de mulheres ao redor do mundo. Além disso, a quimioterapia para tratar neoplasias mamárias afeta diretamente a qualidade de vida relacionada à saúde. Objetivo: Descrever o perfil clínico-epidemiológico e comparar a qualidade de vida relacionada à saúde geral e específica de mulheres com câncer de mama durante a quimioterapia. Método: Estudo observacional e prospectivo com 140 mulheres com câncer de mama no Nordeste do Brasil avaliadas no ciclo intermediário e ao final da quimioterapia. A qualidade de vida foi avaliada por um instrumento geral (EORTC-QLQ-C30) e um módulo específico (EORTC-QLQ-BR23). Os dados foram comparados com teste não paramétrico pareado, com nível de significância de 5%. Resultados: Em relação ao perfil clínico-epidemiológico, a mediana da idade foi de 50 anos, 82,9% eram pretas ou pardas e 95% moravam em Sergipe, Brasil. Além disso, 50,7% não possuíam ocupação, a mediana da renda familiar foi de um salário-mínimo, bem como a mediana da escolaridade foi de oito anos de estudo, e somente 40,7% tinham ensino médio completo. Considerando os dados dos questionários C30 e BR23, observou-se que a maior parte dos itens e escalas piorou ao final da quimioterapia quando comparados ao ciclo intermediário. Entre os itens e escalas com diferenças significativas, a maioria apresentou tamanho de efeito moderado ou alto. Conclusão: É possível concluir que o perfil clínico-epidemiológico foi desfavorável, e a quimioterapia reduziu diversos aspectos da qualidade de vida relacionada à saúde de mulheres com câncer de mama

Introducción: El cáncer de mama puede afectar a diferentes perfiles de mujeres en todo el mundo. Además, la quimioterapia para tratar las neoplasias de mama afecta directamente la calidad de vida relacionada con la salud. Objetivo: Describir el perfil clínico-epidemiológico y comparar la calidad de vida relacionada con la salud general y específica de mujeres con cáncer de mama durante quimioterapia. Método: Estudio observacional y prospectivo con 140 mujeres con cáncer de mama en el Noreste de Brasil evaluadas en la mitad del ciclo y al final de la quimioterapia. La calidad de vida se evaluó mediante un instrumento general (EORTC-QLQ-C30) y un módulo específico (EORTC-QLQ-BR23). Los datos se compararon con una prueba pareada no paramétrica, con un nivel de significación del 5%. Resultados: En cuanto al perfil clínico-epidemiológico, la mediana de edad fue de 50 años, el 82,9% eran negros o mestizos y el 95% vivían en Sergipe, Brasil. Además, el 50,7 % no tenía ocupación, la renta familiar mediana era de un salario mínimo, así como el nivel educativo medio era de ocho años de estudio y solo el 40,7 % tenían la secundaria completa. Considerando los datos de los cuestionarios C30 y BR23, se observó que la mayoría de los ítems y escalas empeoró al final de la quimioterapia en comparación con el ciclo intermedio. Entre los ítems y escalas con diferencias significativas, la mayoría tuvo tamaños del efecto moderados o altos. Conclusión: Es posible concluir que el perfil clínico-epidemiológico fue desfavorable y la quimioterapia redujo varios aspectos de la calidad de vida relacionada con la salud de las mujeres con cáncer de mama

Cold thinking on ten hot issues in the treatment of early breast cancer / 中华外科杂志

With the development of new strategies like target therapy and immunotherapy, early breast cancer treatment has become more standardized, and the interval of disease free survival has been extended. Although guidelines and expert consensus have provided supports for clinical decision making, there are still some controversial issues in clinical practice, attributing to different treatment concepts, product indications and accessibility. These controversial issues would eventually affect the treatment of early breast cancer. This year in 2021, the approval of new indications of drugs like abemaciclib and the popularity of dual anti-human epidermal growth factor receptor 2 targeted drugs have promoted the change of treatment modalities for different types of early breast cancer. To this end, ten hot topics of early breast cancer are summarized according to their different molecular typing and treatment stages for discussion.

Bioactive constituents of animal-derived traditional Chinese medicinal materials for breast cancer: opportunities and challenges / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Breast cancer is globally the most common invasive cancer in women and remains one of the leading causes of cancer-related deaths. Surgery, radiotherapy, chemotherapy, immunotherapy, and endocrine therapy are currently the main treatments for this cancer type. However, some breast cancer patients are prone to drug resistance related to chemotherapy or immunotherapy, resulting in limited treatment efficacy. Consequently, traditional Chinese medicinal materials (TCMMs) as natural products have become an attractive source of novel drugs. In this review, we summarized the current knowledge on the active components of animal-derived TCMMs, including Ophiocordycepssinensis-derived cordycepin, the aqueous and ethanolic extracts of O.sinensis, norcantharidin (NCTD), Chansu, bee venom, deer antlers, Ostreagigas, and scorpion venom, with reference to marked anti-breast cancer effects due to regulating cell cycle arrest, proliferation, apoptosis, metastasis, and drug resistance. In future studies, the underlying mechanisms for the antitumor effects of these components need to be further investigated by utilizing multi-omics technologies. Furthermore, large-scale clinical trials are necessary to validate the efficacy of bioactive constituents alone or in combination with chemotherapeutic drugs for breast cancer treatment.

Huangqi Sijunzi decoction for treating cancer-related fatigue in breast cancer patients: a randomized trial and network pharmacology study / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy of Huangqi Sijunzi decoction (HQSJZD) for treating cancer-related fatigue (CRF) of spleen and stomach Qi deficiency type after chemotherapy in patients with breast cancer.@*METHODS@#A total of 94 breast cancer patients who developed CRF of spleen and stomach Qi deficiency type after chemotherapy were randomized into chemotherapy group (n=47) and traditional Chinese medicine (TCM) + chemotherapy group (n=47). The patients in chemotherapy group received the AC or EC regimen and non-drug interventions including psychological counseling, and those in TCM + chemotherapy group received oral administration of HQSJZD in addition to chemotherapy for 21 days as a treatment cycle, after which improvement of fatigue was assessed using Modified Piper Fatigue Scale. The active ingredients and targets of HQSJZD were screened using the TCM System Pharmacology Analysis Platform (TCMSP); the CRF- and breast cancer-related disease targets were retrieved based on data from the GeneCards, NCBI gene and OMIM databases to construct the component-target network and the protein-protein interaction (PPI) network. GO functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes KEGG pathway enrichment analysis of the target genes were performed to construct the component-disease-pathway-target biological network. The binding strength of the major drug ingredients and CRF key targets were predicted using AutoDock software.@*RESULTS@#The scores for somatic fatigue, emotional fatigue and cognitive fatigue, along with the overall fatigue score, showed more significant improvements in TCM+chemotherapy group than in chemotherapy group (P < 0.001), and the response rate reached 89.4% in the combined treatment group. We identified 250 targets for HQSJZD, 2653 CRF-related genes, 15 329 breast cancer-related genes and 161 prescription-disease intersected targets, from which topological analysis identified 66 potential key targets. GO and KEGG enrichment analyses predicted multiple pathways related with the disease. Molecular docking results suggested that the core ingredients of HQSJZD showed high affinities to the key targets AKT1, CASP3, IL6, JUN and VEGFA, among which AKT1 might be the most important target for HQSJZD to treat CRF.@*CONCLUSION@#HQSJZD can obviously improve CRF symptoms in breast cancer patients possibly by regulating multiple signaling pathways including PI3K-Akt through AKT1.

Expert consensus on the management of adverse events of CDK4/6 inhibitors in breast cancer / 中华肿瘤杂志

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors are anti-tumor agents for the treatment of hormone receptor-positive breast cancer. Palbociclib, abemaciclib and dalpiciclib have been approved for the treatment of breast cancer in China. Common adverse effects of CDK4/6 inhibitors include bone marrow suppression, gastrointestinal toxicities, liver dysfunction, and skin or subcutaneous tissue adverse reactions (AEs). The Breast Cancer Expert Group of Chinese Society of Clinical Oncology (CSCO) summarized the incidence, clinical manifestations, and grading of the AEs. This expert consensus reports measures of AE management on the basis of experience of clinical practice and the latest advances worldwide, aiming to guide clinical practice by the way of managing AE and help to choose the best treatment regimen.