The decreased left ventricular ejection fraction in patients using trastuzumab deruxtecan for her2-positive breast cancer: a systematic review and meta-analysis

Breast Cancer (BC) is one of the most common cancers diagnosed in population femmale and it has several subtypes, one of them being theexpressing human epidermal growth factor receptor 2 positive (HER2 +), one of the treatments for HER2+ breast cancer consists of chemotherapy plus trastuzumab deruxtecan. Several clinical trials have shown the effectiveness and safety of trastuzumabe deruxtecano in cancer patients, however, several Adverse Events (AEs) have been described and the decrease in left ventricular ejection has been singled out for more prominent analysis. Objective: We conducted a systematic review and meta-analysis to investigate the cardiovascular effects of Trastuzumab Deruxtecano and whether it can influence the appearance of reduced left ventricular ejection fraction.. METHODS: We performed a systematic search in Embase, PubMed and Cochrane databases for randomized controlled trials (RCTs) showed a decrease in left ventricular ejection fraction in patients using trastuzumab deruxtecan against Her-2-positive breast cancer compared to patients to used another's treatments against this disease. Mean difference (MD) with 95% confidence intervals (CI) were calculated using a random effects model. The heterogeneity was examined in the I2 statistic. P-values > 0.05 were considered statistically significant. The statistical analysis was carried out using R software version 4.2.3. RESULTS: A total of 3 RCTs were included, with a total of 1656 patients evaluated, 928 patients randomized to the use of Trastuzumab Deruxtecan and 728 patients to the use of other treatments according to medical choice, follow-up ranged from 10 to 38 months. There was a visible in the decrease in left ventricular ejection fraction, with a higher incidence in the group that used trastuzumab compared to the placebo group (RR: 5.73%; 95% CI 1.51 - 21.78; I2 33% ; P= 0.010466). Another important point is the discontinuation of treatment due to grade 2 adverse events, classified as reduced LVEF, where a higher incidence is seen in the group that used Trastuzumab Deruxtecan compared to the placebo group (RR 2.11%; 95% CI 1.54 - 2.89; P = 0.000003),7. CONCLUSION: In this meta-analysis, Trastuzumab Deruxtecan showed a relationship with a decrease in left ventricular ejection fraction, displaying the need for more studies to evaluate the cardiotoxicity of trastuzumab and its effects as a whole on the cardiovascular system.

Cardio-protective effects of statins in patients with breast cancer undergoing anthracycline-based chemotherapy: a metaanalysis of randomized controlled trials

BACKGROUND: Contemporary understanding characterizes cardiotoxicity as a reduction in left ventricular ejection fraction (LVEF) by at least 10%, resulting in a final value below 53% in successive assessments. Nevertheless, breast cancer therapy can impact the cardiovascular system through various avenues. Cardiotoxicity is a known side effect of anthracycline chemotherapy, and the effectiveness of concomitant statin use in mitigating this risk is still unclear. PURPOSE: We aimed to evaluate the potential cardioprotective effects of statin exposure during anthracycline treatment. Our hypothesis posited that patients receiving statins during their treatment would experience a lesser decline in left ventricular ejection fraction (LVEF), lower levels of cholesterol and a reduced occurrence of cardiotoxicity compared to those not exposed to statins. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing statin versus placebo in patients undergoing anthracycline therapy. We searched PubMed, Embase and Cochrane for eligible trials. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was examined with I2 statistics. P values of < 0.05 were considered statistically significant. Statistical analysis were performed using R software version 4.2.3. RESULTS: A total of 4 RCTs comprising 580 patients were included, of whom 281 were randomized to statins and 299 to placebo. The follow up period ranged from 2.5 to 24 months, with participant ages varying between 36 to 68.9 in the intervention group and 37.9 to 72 in the control group. Compared with placebo, statins were significantly associated with a higher left ventricular ejection fraction (MD 2.57%; 95% CI 1.05-4.08; p<0.001; I2=0%), reduction in left ventricular systolic end-volume (MD -4.5 mL; 95% CI -7.57 to -1.44; p<0.004; I2=0%) and diastolic end-volume (MD -6.08 mL; 95% CI -11.27 to -0.9; p<0.021; I2=0%), with a low heterogeneity value. Statins also showed important reduction of total cholesterol (MD -46.28 mg/dL; 95% CI -71.3 to -21.25; p<0.001; I2=89%) and LDL-C (MD -39.45 mg/dL; 95% CI -52.27 to -26.64; p<0.001; I2=84%). CONCLUSIONS: In this metaanalysis of RCTs, the use of statins showed a correlation with improved cardiovascular parameters, indicating their effectiveness in minimizing cardiotoxicity in breast cancer patients undergoing anthracycline chemotherapy

[Cardiotoxicity from anti-HER-2 therapies in patients with HER-2 positive breast cancer]. / Cardiotoxicidad por terapias anti-HER-2 en pacientes con cáncer de mama HER-2 positivo.

Background: HER-2 positive (+) breast cancer (BC) accounts for 20-25% of BC, it is more aggressive, and it has a lower survival rate. Since the approval of trastuzumab in 1998, other HER-2-targeted therapies such as pertuzumab and trastuzumab emtansine (TDM1) have been introduced, improving patient survival. However, cardiotoxicity is an adverse effect of these treatments. Objective: To estimate the incidence of cardiotoxicity with trastuzumab, trastuzumab/pertuzumab, and TDM1 in women with HER-2 + BC treated over a 6-year period at the Hospital de Clínicas and the Hospital Departamental de Soriano. Material and methods: Observational, descriptive, and retrospective study which included patients with HER-2 + BC treated with trastuzumab, trastuzumab/pertuzumab, or TDM1. Results: 81 patients were included, with a cardiotoxicity incidence of 23.4%. Cardiotoxicity was determined by a > 10% decrease in left ventricular ejection fraction (LVEF) (57.9%) and a LVEF < 50% evident during treatment (42.1%). Only 1 patient presented symptomatic heart failure. 63.1% of those who discontinued treatment due to cardiotoxicity managed to resume it. No relationship was evident between cardiovascular history or the administration regimen and the development of cardiotoxicity. Conclusion: The study showed a cardiotoxicity incidence similar to the international one. Most did not present cardiac toxicity, and if they did, it was asymptomatic and reversible.

Introducción: el cáncer de mama (CM) HER-2 positivo (+) representa el 20-25% de los CM, es más agresivo y tiene menor sobrevida. Desde la aprobación del trastuzumab en 1998, se han introducido otras terapias dirigidas al HER-2 como pertuzumab y trastuzumab emtansina (TDM1), con lo cual ha mejorado la supervivencia de las pacientes. Sin embargo, la cardiotoxicidad representa un efecto adverso de estos tratamientos. Objetivo: estimar la incidencia de cardiotoxicidad con trastuzumab, trastuzumab/pertuzumab y TDM1 en mujeres con CM HER-2 +, tratadas en un periodo de 6 años en el Hospital de Clínicas y el Hospital Departamental de Soriano. Material y métodos: estudio observacional, descriptivo y retrospectivo que incluyó pacientes con CM HER-2 +, tratadas con trastuzumab, trastuzumab/pertuzumab o TDM1. Resultados: se incluyeron 81 pacientes. La incidencia de cardiotoxicidad fue del 23.4%. La cardiotoxicidad se determinó por una disminución > 10% de la fracción de ejección del venticulo izquierdo (FEVI) (57.9%) y por una FEVI < 50%, evidenciada durante el tratamiento (42.1%). Únicamente una paciente presentó insuficiencia cardiaca sintomática. El 63.1% de quienes suspendieron el tratamiento por cardiotoxicidad logró reanudarlo. No se evidenció una relación entre los antecedentes cardiovasculares ni con el esquema de administración y el desarrollo de cardiotoxicidad. Conclusión: el estudio mostró una incidencia de cardiotoxicidad similar a la internacional. La mayoría no tuvo toxicidad cardiaca y si la hubo fue asintomática y reversible.

Phase angle as a potential tool to evaluate chronic inflammatory state and predict quality of life deterioration in women with breast cancer and obesity: A narrative review.

The interaction between lifestyle--defined more specifically in health care as the personal exposome--and its implications on obesity and breast cancer development highlights the critical role of body composition and inflammation in these patients. There is clear evidence that the personal and internal exposome triggers biochemical, inflammatory, and metabolic reprogramming, which might favor ectopic lipid accumulation within the body, such as muscles. Additionally, the presence of excessive adipose tissue exacerbates these alterations in the internal exposome, resulting in cell damage and modifying body composition. Understanding the nexus between these lifestyle-induced exposome modifications, such as inflammation, and the resultant changes in body composition is crucial to assess the association with breast cancer progression and treatment responses. Various techniques can be used to evaluate body composition; one of those most used currently is bioelectrical impedance analysis. This analysis provides parameters, including phase angle (PhA), by which cellular health and metabolic activity can be assessed. In addition, PhA is a potential indicator of nutritional status and disease prognosis, as it has been linked to survival and quality of life in patients with cancer. Therefore, PhA might be used in daily oncology practice to implement an accurate nutritional intervention, reducing side effects and complications of oncology management, and improving quality of life during treatment and survival, even in patients with breast cancer with obesity or overweight. The aim of this review is to analyze the existing information on the current application of PhA in patients with breast cancer and its potential use as a tool to assess inflammatory response, identify malnutrition, and predict the deterioration of quality of life so that it could be proposed as an early indicator for nutritional interventions in this group of patients.

Hereditary breast cancer next-generation sequencing panel evaluation in the south region of Brazil: A novel BRCA2 candidate pathogenic variant is reported.

BACKGROUND: In this article, we delineate a loosely selected cohort comprising patients with a history of early-onset breast cancer and/or a familial occurrence of cancer. The aim of this study was to gain insights into the presence of breast cancer-related gene variants in a population from a micro-region in southern Brazil, specifically the Metropolitan Region of Curitiba. This area exhibits a highly genetically mixed population, mirroring the general characteristics of the Brazilian people. METHODS: Comprehensive next-generation sequencing (NGS) multigene panel testing was conducted on 12 patients from the region, utilizing three different library preparation methods. RESULTS: Two pathogenic variants and one candidate pathogenic variant were identified: BRCA2 c.8878C>T, p.Gln2960Ter; CHEK2 c.1100del, p.Thr367Metfs15, and BRCA2 c.3482dup, p.Asp1161Glufs3. CONCLUSION: BRCA2 c.3482dup, a novel candidate pathogenic variant, previously unpublished, is reported. The prevalence of pathogenic variants in this small cohort is similar to that described in the literature. All different library preparation methods were equally proficient in enabling the detection of these variants.

Annonaceae acetogenins: A potential treatment for gynecological and breast cancer.

Breast and gynecological cancers are major health concerns due to their increasing incidence rates, and in some cases, their low survival probability. In recent years, multiple compounds of natural origin have been analyzed as alternative treatments for this disease. For instance, Acetogenins are plant secondary metabolites from the Annonaceae family, and its potential anticancer activity has been reported against a wide range of cancer cells both in vitro and in vivo. Several studies have demonstrated promising results of Acetogenins' antitumor capacity, given their selective activity of cellular inhibition at low concentrations. This review outlines the origin, structure, and antineoplastic activities in vitro and in vivo of Acetogenins from Annonaceae against breast cancer and gynecological cancers reported to date. Here, we also provide a systematic summary of the activity and possible mechanisms of action of Acetogenins against these types of cancer and provide references for developing future therapies based on Acetogenins and nanotechnologies.

Weakly-supervised deep learning models enable HER2-low prediction from H &E stained slides.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a new subtype of tumor, for which novel antibody-drug conjugates have shown beneficial effects. Assessment of HER2 requires several immunohistochemistry tests with an additional in situ hybridization test if a case is classified as HER2 2+. Therefore, novel cost-effective methods to speed up the HER2 assessment are highly desirable. METHODS: We used a self-supervised attention-based weakly supervised method to predict HER2-low directly from 1437 histopathological images from 1351 breast cancer patients. We built six distinct models to explore the ability of classifiers to distinguish between the HER2-negative, HER2-low, and HER2-high classes in different scenarios. The attention-based model was used to comprehend the decision-making process aimed at relevant tissue regions. RESULTS: Our results indicate that the effectiveness of classification models hinges on the consistency and dependability of assay-based tests for HER2, as the outcomes from these tests are utilized as the baseline truth for training our models. Through the use of explainable AI, we reveal histologic patterns associated with the HER2 subtypes. CONCLUSION: Our findings offer a demonstration of how deep learning technologies can be applied to identify HER2 subgroup statuses, potentially enriching the toolkit available for clinical decision-making in oncology.

A New Mixture Model With Cure Rate Applied to Breast Cancer Data.

We introduce a new modelling for long-term survival models, assuming that the number of competing causes follows a mixture of Poisson and the Birnbaum-Saunders distribution. In this context, we present some statistical properties of our model and demonstrate that the promotion time model emerges as a limiting case. We delve into detailed discussions of specific models within this class. Notably, we examine the expected number of competing causes, which depends on covariates. This allows for direct modeling of the cure rate as a function of covariates. We present an Expectation-Maximization (EM) algorithm for parameter estimation, to discuss the estimation via maximum likelihood (ML) and provide insights into parameter inference for this model. Additionally, we outline sufficient conditions for ensuring the consistency and asymptotic normal distribution of ML estimators. To evaluate the performance of our estimation method, we conduct a Monte Carlo simulation to provide asymptotic properties and a power study of LR test by contrasting our methodology against the promotion time model. To demonstrate the practical applicability of our model, we apply it to a real medical dataset from a population-based study of incidence of breast cancer in São Paulo, Brazil. Our results illustrate that the proposed model can outperform traditional approaches in terms of model fitting, highlighting its potential utility in real-world scenarios.

The Expression Profiles of lncRNAs Are Associated with Neoadjuvant Chemotherapy Resistance in Locally Advanced, Luminal B-Type Breast Cancer.

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.

[Neuroendocrine expression markers in triple-negative, luminal-A, luminal-B and HER2neu breast cancer]. / Expresión de marcadores neuroendócrinos en cáncer de mama triple-negativo, luminal-A, luminal-B y HER2neu.

Background: Primary breast tumors with neuroendocrine (NE) differentiation are a heterogeneous tumor group with diversity of biological behavior, with poorly defined prevalence and prognosis. Objective: To evaluate the chromogranin, synaptophysin, CD56, INSM1 markers expression prevalence and the association between NE differentiation and tumor molecular type. Material and methods: Observational, cross-sectional study which included 110 breast tissue samples with primary invasive carcinoma. Immunohistochemistry was performed for chromogranin, synaptophysin, CD56 and INMS1 markers. NE differentiation was considered with 10-90% positive cells, and NE tumor with > 90% positive cells. Results: 26.3% showed neuroendocrine differentiation. Out of these, 48.2% were luminal-A type, 24.1% luminal-B, 11.5% HER2neu, 17.2% triple-negative; 1.8% were NE tumors. Tumors were marker positive, and out of these to chromogranin in 24.5%, synaptophysin in 28.2%, CD56 in 2.7%, INSM1 in 16.4%. Synaptophysin was expressed in 17.3% luminal-A type, 6.4% luminal-B, 0.9% HER2neu, 3.6% triple-negative. NE differentiation showed association with synaptophysin expression (r = 0.586, p = 0.0001). Conclusion: The NE differentiation prevalence was 26.3% in primary invasive breast cancers, with luminal-A molecular type predominance.

Introducción: los tumores primarios de mama con diferenciación neuroendócrina (NEBC por sus siglas en inglés) son un grupo heterogéneo de tumores con diversidad de comportamiento biológico, con prevalencia y pronóstico poco definido. Objetivo: evaluar la prevalencia de la expresión los marcadores cromogranina, sinaptofisina, CD56, INSM1 y la asociación entre la diferenciación neuroendócrina y el tipo molecular del tumor. Material y métodos: estudio observacional, transversal que incluyó 110 muestras de tejido mamario con carcinoma invasor primario. Se realizó inmunohistoquímica para los marcadores cromogranina, sinaptofisina, CD56 y INMS1. La presencia 10-90% de células positivas se consideró diferenciación neuroendócrina y tumor neuroendócrino con > 90% de células positivas. Resultados: el 26.3% mostró diferenciación neuroendócrina. De estos, 48.2% fueron tipo luminal-A, 24.1% luminal-B, 11.5% HER2neu y 17.2% triple-negativo; 1.8% resultaron tumores neuroendócrinos. Los tumores presentaron marcadores positivos y de estos, 24.5% fueron a cromogranina, 28.2% a sinaptofisina, 2.7% a CD56 y 16.4% a INSM1. La sinaptofisina se expresó en 17.3% del tipo luminal-A, 6.4% luminal-B, 0.9% HER2neu, 3.6% triple-negativo. La diferenciación neuroendócrina mostró asociación con la expresión de sinaptofisina (r = 0.586, p = 0.0001). Conclusión: la prevalencia de la diferenciación neuroendócrina fue del 26.3% en los cánceres invasores primarios de mama, con predominio en el tipo molecular luminal-A.

[BIRADS 0 patient reclassification in a first-level of care unit]. / Reclasificación de pacientes BIRADS 0 en una unidad de primer nivel de atención.

Background: In Mexico and the world, breast cancer is the cancer type with the highest incidence and mortality for women. Its incidence has increased due to a higher life expectancy and a higher exposure to risk factors. Screening is done by mammography using the BIRADS (Breast Imaging Reporting and Data System) system, the standard for mammography screening report which classifies lesions assigning recommendations for patient follow-up. The system goes from 0 (not conclusive) to 6 (demonstrated malignancy), being of interest for this study the BIRADS 0 category. Objective: To describe patients classified as BIRADS 0 by mammography and their reclassification in a first-level hospital during 2021. Material and methods: Retrospective, descriptive, cross-sectional, observational study. Women over 40 years with a BIRADS 0 result were studied. The following databases were used: Institutional Cancer Registry, Family Medicine Information System, Electronic Clinical File, and the mammography and patient list from preventive medicine. Results: Reclassification by ultrasound (US) was achieved in 100% of patients, in all of the BIRADS US categories. In 3.8% of BIRADS 0 patients, ductal adenocarcinoma was found and confirmed by histological testing. Conclusion: All of the reassessed lesions with US were adequately reclassified.

Introducción: en México y el mundo, el cáncer de mama causa la mayor mortalidad por cáncer en mujeres. Su incidencia ha incrementado por una mayor esperanza de vida y exposición a factores de riesgo. El tamizaje de esta enfermedad se hace mediante mastografía, y para la estratificación de las lesiones se utiliza el sistema BIRADS (Breast Imaging Reporting and Data System), que estandariza el informe, categoriza las lesiones según el grado de sospecha y asigna recomendaciones a seguir. Dicho sistema va desde 0 (no concluyente) hasta 6 (lesión con malignidad demostrada) y es de interés para este estudio la categoría 0. Objetivo: describir la reclasificación de pacientes con reporte BIRADS 0 por mastografía durante 2021 en una unidad de primer nivel de atención. Material y métodos: estudio retrospectivo, descriptivo, transversal, observacional. Se estudiaron mujeres mayores de 40 años con resultado BIRADS 0. Se utilizaron las siguientes bases de datos: Registro Institucional de Cáncer, Sistema de Información de Medicina Familiar, Expediente Clínico Electrónico y lista nominal de mastografías y censo de pacientes sospechosos de medicina preventiva. Resultados: la reclasificación con ultrasonido (US) se logró en el 100% de pacientes, en todas las categorías de BIRADS US. En el 3.8% se confirmó carcinoma ductal por histología en las pacientes inicialmente categorizadas como BIRADS 0. Conclusiones: la totalidad de lesiones reevaluadas con US fueron reclasificadas satisfactoriamente.

Land- and water-based aerobic exercise program on health-related outcomes in breast cancer survivors (WaterMama): study protocol for a randomized clinical trial.

BACKGROUND: Breast cancer is a prevalent form of cancer among women worldwide, often accompanied by physical and psychological side effects due to the disease and the treatment's aggressiveness. Regular physical exercise has emerged as a non-pharmacological approach to improve the quality of life of breast cancer survivors. We herein report the protocol of the WaterMama Study, which aims to evaluate the effects of land- or water-based aerobic exercise programs, compared to a health education program, on cancer-related fatigue and other health-related outcomes in breast cancer survivors. METHODS: The WaterMama trial is a randomized, single-blinded, three-arm, parallel, superiority trial. We aim to recruit 48 women ≥ 18 years of age who have completed primary treatment for stage I-III breast cancer. Participants are randomly allocated in a 1:1:1 ratio to 12-week interventions of aerobic exercise training programs either in the aquatic or land environment (two weekly 45-min sessions) plus health education (a weekly 45-min session), or an active-control group receiving health education alone (a weekly 45-min session). The primary outcome is cancer-related fatigue, and the secondary outcomes include cardiorespiratory fitness, muscular performance, muscle morphology, functional capacity, mental health, cognitive function, pain, and quality of life. Outcomes assessments are conducted before and after the 12-week intervention period. The analysis plan will employ an intention-to-treat approach and per protocol criteria. DISCUSSION: Our conceptual hypothesis is that both aerobic exercise programs will positively impact primary and secondary outcomes compared to the health education group alone. Additionally, due to its multi-component nature, we expect the aquatic exercise program promote more significant effects than the land exercise program on cancer-related fatigue, muscular outcomes, and pain. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov NCT05520515. Registered on August 26, 2022. https://clinicaltrials.gov/ct2/show/NCT05520515.

A Research Protocol for a Phase II Single-Arm Clinical Trial Assessing the Feasibility and Efficacy of Neoadjuvant Anastrozole in Patients With Luminal Breast Cancer and Low Proliferative Index: The ANNE Trial.

INTRODUCTION: Neoadjuvant endocrine therapy (NET) is recommended for the treatment of invasive breast cancer (BC), particularly luminal subtypes, in locally advanced stages. Previous randomized studies have demonstrated the benefits of aromatase inhibitors in this context. However, NET is typically reserved for elderly or frail patients who may not tolerate neoadjuvant chemotherapy. Identifying non-responsive patients early and extending treatment for responsive ones would be ideal, yet optimal strategies are awaited. AIMS: This non-randomized phase 2 clinical trial aims to assess NET feasibility and efficacy in postmenopausal stage II and III luminal BC patients, identifying predictive therapeutic response biomarkers. Efficacy will be gauged by patients with Ki67 ≤ 10% after 4 weeks and Preoperative Endocrine Prognostic Index (PEPI) scores 0 post-surgery. Study feasibility will be determined by participation acceptance rate (recruitment rate ≥50%) and inclusion rate (>2 patients/month). METHODS: Postmenopausal women with luminal, HER2-tumors in stages II and III undergo neoadjuvant anastrozole treatment, evaluating continuing NET or receiving chemotherapy through early Ki67 analysis after 2 to 4 weeks. The study assesses NET extension for up to 10 months, using serial follow-ups with standardized breast ultrasound and clinical criteria-based NET suspension. Clinical and pathological responses will be measured overall and in the luminal tumor A subgroup. Toxicity, health-related quality of life, and circulating biomarkers predicting early NET response will also be evaluated.

Postmenopausal women treated for breast cancer with insulin resistance: clinical, analytical, cross-sectional.

This study aims to investigate the potential association between serum levels of cytokines, HSP60, HSP70 and IR (HOMA-IR) in postmenopausal women. We conducted a cross-sectional study involving 381 postmenopausal women, including 94 with a breast cancer diagnosis and 278 without. We analyzed anthropometric and laboratory measurements. Immunoassays were used to measure cytokines (TNF-α, IL-10, and IL-6) as well as heat shock proteins (HSP) 60 and 70 in the serum using the ELISA technique. Women diagnosed with breast cancer showed higher levels of HOMA-IR, IL-6, TNF, and HSP60, and lower levels of IL-10 and HSP70 compared to women without cancer. An association was found between HSP70 and HOMA-IR only in women with breast cancer (ß = 0.22, p = .030; without cancer: ß = 0.04, p = .404), regardless of age, waist circumference, smoking, and physical activity. No associations were observed between cytokines, HSP60, and HOMA-IR in both groups of women. HSP70 is positively associated with IR in women diagnosed with breast cancer.

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Upregulated Nuclear Expression of Soluble Epoxide Hydrolase Predicts Poor Outcome in Breast Cancer Patients: Importance of the Digital Pathology Approach.

Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10-3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan-Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804-6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC.

Prevention of chemotherapy-related bone loss with doxorubicin-loaded solid lipid nanoparticles.

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model.Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy.Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals.Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.

[Box: see text].

Reliability of dynamic and isometric upper muscle strength testing in breast cancer survivors.

Breast cancer is the most common cancer in women worldwide, and its treatment usually involves a combination of many medical procedures, including surgery, chemotherapy, radiotherapy, and hormonal therapy. One of the detrimental effects on physical function is reduced upper limb muscle strength. This study aimed to evaluate upper body strength intra-day and inter-day (test-retest) reliability using the handgrip strength test (HGS) and the bilateral isometric bench press (BIBP) and the test-retest reliability of the one repetition maximum on the bench press (BP-1RM) in breast cancer survivors (BCS). Thirty-two (52.94 ± 8.99 yrs) BCS participated in this study. The muscle strength tests were performed in two different moments, three to seven days apart. Intraclass coefficient correlation (ICC) and coefficient of variation (CV) were used to assess the reliability. Standard error of measurement (SEM), typical error of measurement (TEM), and minimally detectable change (MDC) analyses were performed. The Bland-Altman analysis was used to assess the agreement between test-retest. We found a reliability that can be described as "high" to "very high" (ICC ≥ 0.88; CV ≤ 10%) for intra-day and test-retest. SEM% and MDC% were lower than 5% and 11%, respectively, for all intra-day testing. SEM% and TEM% ranged from 3% to 11%, and MDC% ranged from 9% to 23% in the test-retest reliability. The agreement demonstrated a systematic bias ranging from 2.3% to 6.0% for all testing, and a lower systematic bias may be presented in the non-treated side assessed by HGS and BIBP. HGS, BIBP, and BP-1RM assessments are reliable for measuring upper-body muscle strength in BCS.

Mortality of Young Women due to Breast Cancer in Low, Middle and High-Income Countries: Systematic Literature Review and Meta-Analysis.

OBJECTIVE: To identify the difference in breast cancer mortality rates among young women according to countries' economic classification. METHODS: A systematic literature review included retrospective studies on breast cancer mortality rates in women aged 20 to 49 years. Databases used were PubMed, Web of Science, Scopus, and Virtual Health Library, with articles selected in English, Portuguese, and Spanish. The study selection and analysis were conducted by two pairs of researchers. Data from 54 countries were extracted, including 39 high-income, 12 upper-middle-income, and 3 lower-middle-income countries. A meta-analysis was performed with the quantitative data from two studies. RESULTS: Six articles met the inclusion criteria. Four were analyzed descriptively due to data diversity, and two were included in the meta-analysis. The pooled mortality rate for high-income countries was 10.2 per 100,000 women (95% CI: 9.8-10.6), while for upper-middle-income countries, it was 15.5 per 100,000 women (95% CI: 14.9-16.1). Lower-middle-income countries had a pooled mortality rate of 20.3 per 100,000 women (95% CI: 19.5-21.1). The decrease in mortality rates in high-income countries was statistically significant (p<0.05). CONCLUSION: Mortality rates for breast cancer among young women have decreased significantly in high-income countries but have increased in lower-income countries. This disparity underscores the impact of insufficient investment in preventive measures, health promotion, early diagnosis, and treatment on young women's mortality in lower-income countries.

Quality of life in patients treated with breast cancer surgery and adjuvant systemic therapy and/or adjuvant radiotherapy in Uruguay.

INTRODUCTION: Breast cancer (BC) and its treatment can impair patient quality of life (QoL), and those undergoing more aggressive treatments may be more severely impacted. Objective: Assess the level of perception of the QoL of patients treated for BC at the Hospital de Clínicas and the Departmental Hospital of Soriano. MATERIALS AND METHODS: A questionnaire for cancer patients (EORTC, QLQ-C30) and one specific for BC (EORTC QLQ-BR23) were used. RESULTS: A total of 158 patients who had completed chemotherapy treatment at least one year prior to the evaluation were enrolled. The average age was 61 years old. QLQC QUESTIONNAIRE: The global QoL score (GQOL) was high: 70.9. Patients undergoing breast-conservation surgery (BCS) had better scores in physical and emotional functioning (p < 0.005) and presented less frequently with: pain, constipation, and financial difficulties (p < 0.005). Those undergoing sentinel lymph node biopsy (SLNB) had higher scores for GQOL and for physical, role, and social functioning scales (p < 0.001) and had less fatigue, pain, insomnia, and financial difficulties (p < 0.005). QUESTIONNAIRE QLQBR: Sexual functioning and sexual enjoyment scales were relatively low. Patients undergoing BCS had better scores on the functional scales: body image and future outlook; and fewer breast symptoms (p < 0.005). Those undergoing SLNB also had better scores on the functional scales for body image and future outlook future and presented less frequently with symptoms (p < 0.005). CONCLUSION: Uruguayan BC patients experience high values on the GQOL scale; those undergoing BCS and SLNB had better scores on most functional and problem/symptom scales. Patients undergoing BCS had better scores in physical and emotional functioning and presented less frequently with pain, constipation, and financial difficulties. With respect to the type of axillary surgery received, patients who underwent SLNB had higher scores on the GQOL scale and on the physical, role, and social functional scales. The implementation of intervention strategies aimed at improving the quality of life, and the physical and emotional care of patients is recommended.