Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

The RabGEF ALS2 is a hypoxia inducible target associated with the acquisition of aggressive traits in tumor cells.

Tumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia. Specifically, hypoxia augmented ALS2 mRNA and protein levels, and these events involved HIF-1α-dependent transcription, as shown by RNAi, pharmacological inhibition, chromatin immunoprecipitation and bioinformatics analyses, which identified a functional HIF-1α-binding site in the proximal promoter region of ALS2. Moreover, ALS2 and Rab5 activity were elevated both in a model of endogenous HIF-1α stabilization (renal cell carcinoma) and by following expression of stable non-hydroxylatable HIF-1α. Strikingly, ALS2 upregulation in hypoxia was required for Rab5 activation, tumor cell migration and invasion, as well as experimental metastasis in C57BL/6 mice. Finally, immunohistochemical analyses in patient biopsies with renal cell carcinoma showed that elevated HIF-1α correlates with increased ALS2 expression. Hence, this study identifies ALS2 as a novel hypoxia-inducible gene associated with tumor progression and metastasis.

Enseñanzas de desastres naturales y pandemias pueden ayudarnos a afrontar la nueva realidad / Lessons from natural disasters and pandemics can help us face the new reality

Ante los eventos de gran magnitud, la incertidumbre se apodera de las personas y afecta su salud mental a corto, mediano y largo plazo. Tras analizar fenómenos anteriores que han 'sacudido' al mundo, investigadores de Colombia, Chile y España profundizan en el tema y sugieren algunas intervenciones.

In the face of large-scale events, uncertainty takes hold of people and affects their mental health in the short, medium and long term. After analyzing previous phenomena that have 'shaken' the world, researchers from Colombia, Chile and Spain delve into the subject and suggest some interventions.

En busca de una radioterapia más efectiva contra el cáncer / In search of more effective radiotherapy against cancer

Aunque la respuesta varía mucho de un paciente a otro, una de las alternativas idóneas para el tratamiento del cáncer es la radioterapia. Un proyecto colombiano, apoyado por otros países, busca respuestas al porqué de esa variabilidad y cómo optimizar su uso.

Although the response varies greatly from one patient to another, one of the ideal alternatives for cancer treatment is radiotherapy. A Colombian project, supported by other countries, seeks answers to the reason for this variability and how to optimize its use.

Científicos colombianos contribuyen con el control de una de las bacterias hospitalarias más poderosas / Colombian scientists contribute to the control of one of the most powerful hospital bacteria

Una investigación multidisciplinaria, respaldada por la Universidad del Rosario, permitió detectar las causas de un foco de infección producido por una bacteria que puede vivir hasta seis años en objetos y es resistente a los antibióticos. Gracias a ello, se prendieron las alertas sobre las herramientas de prevención.

A multidisciplinary investigation, supported by the Universidad del Rosario, made it possible to detect the causes of a source of infection produced by a bacterium that can live up to six years on objects and is resistant to antibiotics. Thanks to this, alerts on prevention tools were set off.

Con videojuego de realidad virtual se aprende anatomía en la URosario / With a virtual reality video game you learn anatomy in the URosario

Imagine que puede reducirse de tamaño y entrar a la arteria principal, la aorta y, como si fuera en una nave, realizar un completo recorrido por la anatomía, desplazándose por los conductos sanguíneos, descubriendo cada milímetro de esa maravilla que es el cuerpo. Esta experiencia innovadora no es un sueño, es toda una realidad en la Escuela de Medicina y Ciencias de la Salud de la Universidad del Rosario, específicamente en la clase de Anatomía, y hace parte de un proceso de transformación de la enseñanza. En este, tiene un rol importante el videojuego de realidad virtual (VR, por su sigla en inglés) Nanosurgeons Glandula Mamaria, que le permite a los estudiantes profundizar en el cuerpo humano, obtener un conocimiento valioso e inolvidable y, finalmente, ser evaluado.

Imagine that you can reduce in size and enter the main artery, the aorta and, as if it were in a ship, take a complete tour of the anatomy, moving through the blood conduits, discovering every millimeter of that marvel that is the body. This innovative experience is not a dream, it is a reality in the School of Medicine and Health Sciences of the Universidad del Rosario, specifically in the Anatomy class, and it is part of a process of transformation of teaching. In this, the virtual reality (VR) video game Nanosurgeons Glandula Mamaria plays an important role, allowing students to delve into the human body, obtain valuable and unforgettable knowledge and, finally, be evaluated.

Estudiantes de la salud aprenden a trabajar en equipos interprofesionales con una metodología innovadora / A pioneering system with sensors created by scientists from the Universida del Rosario promises to identify real-time learning problems in children. The prototype was presented at the World Congress of Medical Physics and Biomedical Engineering.

Un grupo de docentes de la Universidad del Rosario creó una comunidad de aprendizaje innovadora. En seis semanas, estudiantes de diferentes programas, con tutores de diversas disciplinas de la salud, aprendieron virtualmente a trabajar en equipos interprofesionales usando la resolución de casos.

A group of teachers from the Universidad del Rosario created an innovative learning community. In six weeks, students from different programs, with tutors from various health disciplines, virtually learned to work in interprofessional teams using case resolution.

Beyond grade: molecular pathology of malignant gliomas.

High-grade gliomas (HGGs) represent a heterogenous group of tumors and account for most primary brain tumors. Despite aggressive therapies, they are invariably associated with poor patient outcome. These tumors include the anaplastic (World Health Organization [WHO] grade III) histologies of astrocytomas, oligodendrogliomas, and ependymomas and the WHO grade IV glioblastoma multiforme (GBM). The recent elucidation of the fundamental molecular alterations associated with these tumors has begun to unravel the critical events in their tumorigenesis but for the most part has done little to alter patient survival. Prognostication for patients with these tumors has relied principally on tumor grade and clinical factors (age, performance status, and so on) and has been inexact at best in identifying those with long-term survival potential. An even greater challenge has been to identify predictive biomarkers of therapy in the hope of tailoring a patient's therapy based on their tumor's molecular characteristics. This review discusses the molecular pathology of high-grade gliomas, with particular emphasis on anaplastic astrocytomas and GBMs because these represent the most common forms of malignant gliomas. It also focuses on the molecular signatures defined by large-scale gene expression profiling experiments because these studies are at the forefront in developing new biomarkers and identifying new therapeutic targets.