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BACKGROUND: Tumor budding (TB) is a dynamic process associated with the epithelial-mesenchymal transition and a well-established prognostic biomarker for colorectal cancer. As part of the tumor microenvironment, tumor buds demonstrate increased cell motility and invasiveness. Current evidence demonstrates that high levels of TB correlate with disease progression and worst outcomes across different solid tumors. Our work aims to demonstrate the clinical applicability of TB analysis and its utility as a prognostic factor for patients with early breast cancer (EBC). METHODS: Retrospective, single-center, observational study, enrolling patients with EBC diagnosed in a Portuguese hospital between 2014 and 2015. TB classification was performed according to the International Tumor Budding Conference 2016 guidelines. RESULTS: A statistically significant relation was found between higher TB score and aggressive clinicopathological features (angiolymphatic/perineural invasion-p < 0.001; tumor size-p = 0.012; nuclear grading-p < 0.001; and Ki-67 index-p = 0.011), higher number of relapses (p < 0.001), and short disease-free survival (DFS) (p < 0.001). CONCLUSION: We demonstrate that high TB correlates with shorter DFS and aggressive clinicopathological features used in daily practice to decide on the benefit of chemotherapy for EBC. TB represents a needed prognostic biomarker for EBC, comprising a new factor to be considered in the adjuvant decision-making process by identifying patients at a high risk of relapse and with higher benefit on treatment intensification. Clinical trials incorporating TB are needed to validate its prognostic impact.
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INTRODUCCIÓN: Ceftarolina fosamil es un nuevo antibiótico de última generación del subgrupo de las cefalosporinas. Es el primer beta-lactámico comercializado que presenta actividad frente a Staphylococcus aureus resistente a la meticilina (SARM). El objetivo del presente estudio es determinar los valores in vitro de la concentración mínima inhibitoria (CMI) y de la concentración mínima bactericida (CMB) de ceftarolina frente a cepas de S. aureus, tanto sensible a la meticilina (SASM) como resistente. MATERIAL Y MÉTODOS: Se realizó un estudio multicéntrico en el que participaron 4 hospitales representativos de la geografía española. Mediante el método de microdilución en caldo se determinaron los valores de CMI y CMB de la ceftarolina frente a cepas de S. aureus (SARM y SASM). RESULTADOS: Se analizaron un total de 266 cepas de S. aureus (95 SARM y 171 SASM). En las 266 cepas analizadas, todos los valores de CMI se encontraron dentro de la categoría de sensible (valor ≤ 1 μg/ml), no detectándose ninguna cepa intermedia ni ni resistente. Las CMI50 y CMI90 para SAMR fueron de 0,25 y 0,5 μg/ml, respectivamente, con un rango de 0,125 a 1 μg/ml. Las CMI50 y CMI90 para SASM fueron de 0,125 y 0,25 μg/ml, con un rango de 0,125 a 0,5 μg/ml. Las CMB50 y CMB90 para SAMR fueron de 0,5 y 1 μg/ml, respectivamente, con un rango de 0,125 a 1 μg/ml. Las CMB50 y CMB90 para SASM fueron de 0,25 y 0,25 μg/ml, con un rango de 0,125 a 0,5 μg/ml. CONCLUSIÓN: Ceftarolina muestra una excelente actividad in vitro frente a S.aureus, incluyendo cepas SARM, por lo que podría presentarse como una alternativa prometedora en el tratamiento de infecciones causadas por esta bacteria
INTRODUCTION: Ceftaroline fosamil is a new-generation antimicrobial agent of cephalosporins subgroup. It is the first commercially available beta-lactam antibiotic that exhibits activity against methicillin-resistantStaphylococcus aureus (MRSA). The aim of this study is to determine the in vitro Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of ceftar oline against S. aureus strains (including MRSA). MATERIAL AND METHODS: A multicenter study involving four hospitals representative of the Spanish geography was performed. MIC and MBC values against both the methicillin-resistant and sensitive strains of S. aureus (MRSA and methicillin-sensitive S. aureus [MSSA]) were determined using a broth microdilution method. RESULTS: A total of 266 S. aureus strains were analyzed (95 MRSA and 171 MSSA). Ceftaroline bacterial sensitivity showed a mean MIC of 0.227 μg/ml (SD=0.146; range, 0.06 to 1μg/ml). All MIC values of the 266 strains tested belonged to the sensitive category (value ≤1μg/ml). Intermediate or resistant strains were not detected. MIC50 and MIC90 values for MRSA were 0.25 and 0.5μg/ml, respectively (range = 0.125-1 μg/ml). MSSA strains showed MIC50 and MIC90 values of 0.125 and 0.25 μg/ml, respectively (range = 0.125-0.5 μg/ml). MBC50 and MBC90 values for MRSA were 0.5 and 1μg/ml, respectively (range = 0.125-1μg/ml). MSSA strains showed MBC50 and MBC90 values of 0.25 and 0.25 μg/ml, respectively (range = 0.125-0.5 μg/ml). CONCLUSIÓN: Ceftaroline shows excellent in vitro activity against S.aureus, including MRSA strains. Therefore, this antibiotic may be a promising alternative for the treatment of infections caused by this bacterium
Subject(s)
Humans , Staphylococcus aureus/pathogenicity , Staphylococcal Infections/drug therapy , Anti-Bacterial Agents/pharmacokinetics , Microbial Sensitivity Tests/methods , Drug Resistance, MicrobialABSTRACT
INTRODUCTION: Ceftaroline fosamil is a new-generation antimicrobial agent of cephalosporins subgroup. It is the first commercially available beta-lactam antibiotic that exhibits activity against methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study is to determine the in vitro Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of ceftaroline against S.aureus strains (including MRSA). MATERIAL AND METHODS: A multicenter study involving four hospitals representative of the Spanish geography was performed. MIC and MBC values against both the methicillin-resistant and sensitive strains of S.aureus (MRSA and methicillin-sensitive S.aureus [MSSA]) were determined using a broth microdilution method. RESULTS: A total of 266 S.aureus strains were analyzed (95 MRSA and 171 MSSA). Ceftaroline bacterial sensitivity showed a mean MIC of 0.227 µg/ml (SD=0.146; range, 0.06 to 1 µg/ml). All MIC values of the 266 strains tested belonged to the sensitive category (value ≤ 1 µg/ml). Intermediate or resistant strains were not detected. MIC50 and MIC90 values for MRSA were 0.25 and 0.5 µg/ml, respectively (range=0.125-1 µg/ml). MSSA strains showed MIC50 and MIC90 values of 0.125 and 0.25 µg/ml, respectively (range=0.125-0.5 µg/ml). MBC50 and MBC90 values for MRSA were 0.5 and 1 µg/ml, respectively (range=0.125-1 µg/ml). MSSA strains showed MBC50 and MBC90 values of 0.25 and 0.25 µg/ml, respectively (range=0.125-0.5 µg/ml). CONCLUSION: Ceftaroline shows excellent in vitro activity against S.aureus, including MRSA strains. Therefore, this antibiotic may be a promising alternative for the treatment of infections caused by this bacterium.
