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).Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Cancer; BrasilFil: Artagaveytia, Nora. Universidad de la Republica; UruguayFil: Daneri Navarro, Adrián. Universidad de Guadalajara; MéxicoFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: Velazquez, Carlos. Universidad de Sonora; MéxicoFil: Alcoba, Elsa B.. Hospital Maria Curie; ArgentinaFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; UruguayFil: Alves Da Quinta, Daniela Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Universidad Argentina de la Empresa; ArgentinaFil: Binato, Renata. Instituto Nacional de Cancer; BrasilFil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Camejo, Natalia. Universidad de la Republica; UruguayFil: Carraro, Dirce Maria. Centro Internacional de Pesquisa; BrasilFil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Castro Cervantes, Juan M.. Umae Hospital de Especialidades Centro Medico Nacional Siglo XXI; MéxicoFil: Cataldi, Sandra. Instituto Nacional del Cáncer; UruguayFil: Cayota, Alfonso. Instituto Pasteur de Montevideo; UruguayFil: Cerda, Mauricio. Universidad de Chile; ChileFil: Colombo, Alicia. Universidad de Chile; ChileFil: Crocamo, Susanne. National Cancer Institute; Estados UnidosFil: Del Toro Arreola, Alicia. Universidad de Guadalajara; MéxicoFil: Delgadillo Cisterna, Raúl. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Delgado, Lucía. Universidad de la Republica; UruguayFil: Fernandez, Elmer Andres. Area de Cs. Agrarias, Ingeniería, Cs. Biológicas y de la Salud de la Universidad Catollica de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Fejerman, Laura. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; ArgentinaFil: Valenzuela, Olivia. Universidad de Sonora; MéxicoFil: Vedham, Vidya. National Cancer Institute; Estados UnidosFil: Zagame, Livia. Instituto Jalisciense de Cancerología; MéxicoFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Immunobiology of HPV Infection

[No abstract available

Information and emotional support for women with abnormal pap test results [Información y soporte emocional a las mujeres con resultado anormal en Papanicolaou: Una guía de comunicación]

The aim of the present study was to develop and to evaluate a guide to communicate the presence and treatment of Papanicolaou alterations that suggest dysplasia or cervical cancer. Method: A sample of 97 women with abnormal smear test referred to diagnosis and treatment at a third level hospital were interviewed pre and post an informative session systematized in the proposed guide, to compare the degree of information about their condition and treatment and their perception of emotional support from health professionals. Results: The communication guide were developed according evidence based treatment model. We documented a pre-post clinical and statistical difference in the level of information about their condition and treatment (3.97 ± 3.15 vs. 8.15 ± 2.65; t= -7.27, df= 53, p?.0001), and a tendency of increment in the percentage of patients that perceived emotional support from health professionals (62.3% vs. 100%; chi square=31.18, df=1, p=.07). Conclusions: The guide presented here constitutes a useful material to improve communication of these conditions and its treatment among Hispanic women with low level of education

Information and emotional support for women with abnormal pap test results [Información y soporte emocional a las mujeres con resultado anormal en Papanicolaou: Una guía de comunicación]

The aim of the present study was to develop and to evaluate a guide to communicate the presence and treatment of Papanicolaou alterations that suggest dysplasia or cervical cancer. Method: A sample of 97 women with abnormal smear test referred to diagnosis and treatment at a third level hospital were interviewed pre and post an informative session systematized in the proposed guide, to compare the degree of information about their condition and treatment and their perception of emotional support from health professionals. Results: The communication guide were developed according evidence based treatment model. We documented a pre-post clinical and statistical difference in the level of information about their condition and treatment (3.97 ± 3.15 vs. 8.15 ± 2.65; t= -7.27, df= 53, p≤.0001), and a tendency of increment in the percentage of patients that perceived emotional support from health professionals (62.3% vs. 100%; chi square=31.18, df=1, p=.07). Conclusions: The guide presented here constitutes a useful material to improve communication of these conditions and its treatment among Hispanic women with low level of education

Endothelial cells promote pancreatic stem cell activation during islet regeneration in mice

Objectives: Diabetes is the clinical consequence of the loss of the majority of the ?-cell population and failure to regenerate new pancreatic ? cells. The current therapies based on ?-cell replacement have failed to achieve ?-cell renewal and thus, long-term insulin freedom. We have hypothesized that early rejection of endothelial elements within the islet grafts may seriously hamper islet regeneration in both native and islet grafts. Methods: In the present study, we analyzed the role of endothelial cells to activate pancreatic stem cells during islet regeneration. Mice were pretreated with or without endothelial pharmacological ablation of endothelial cells, followed by an acute ?-cell injury using a single intraperitoneal injection of streptozotocin. We performed comparative morphometric analyses of recovered pancreata on days 3, 7, 10, and 30 after streptozotocin injury, staining with bromodeoxyuridine (BrdU) for representative cell types, ? cells, endothelial elements, and stem cells. Blood glucose levels were measured continuously after the injury to monitor the capacity for metabolic control. Results: Morphometric analyses revealed an increasing number of cells over time to be stained with a stem cell and BrdU markers among animals only injured with streptozotocin but not with endothelial ablation. Notably, on day 10, stem cell markers were dramatically decrease nearly to basal levels, with appearance of numerous insulin-positive cells. Intact vessels with cobblestone-shaped endothelial elements were observed in direct proportion to the better outcomes, both by morphometric and by metabolic parameters. In contrast, fewer insulin-positive cells were observed in pancreata that had been ablated of endothelial cells showing extensive collapse of endocrine functions. Conclusions: We observed that endothelial elements promoted stem cell proliferation and islet regeneration after a ?-cell insult. We believe that preservation of endothelial cells positively affects the process of pancreatic regeneration. © 2011 Published by Elsevier Inc

The antitumoral effect of lymphokines and a single dose of cyclophosphamide in mice with mirine lymphoma [SINERGISMO ANTITUMORAL DE LINFOCINAS Y DOSIS UNICA DE CICLOFOSFAMIDA EN RATONES CON LINFOMA MURINO]

[No abstract available

The antitumoral effect of lymphokines and a single dose of cyclophosphamide in mice with mirine lymphoma [SINERGISMO ANTITUMORAL DE LINFOCINAS Y DOSIS UNICA DE CICLOFOSFAMIDA EN RATONES CON LINFOMA MURINO]

[No abstract available

Exploratory study of the relationship between the perception of instrumental social support and changing family roles in women with breast cancer [Estudio exploratorio de relación entre la percepción de apoyo social instrumental y la modificación de roles familiares en mujeres con cáncer de mama]

Objective: To explore the relationship between the sources and types of instrumental support provided to women with breast zancer, with changes in roles and daily activities in patients and their relatives.Methods: Qualitative study focused on the ethnography of 9 patients with nreast cancer. Through MAXQDA v10 software, we did a thematic analysis of discourse and developed cross tables for the analysis of the study variables.Results: For these women, the nuclear family is the main source of instrumental support, also are who often modify their daily activities and social roles. Women with breast cancer expressed difficulty delegating household chores, principally due to three reasons: Her mother's responsibility, a sense of usefulness and traditional gender ideology.Conclusions: The impact of cancer in women has unique consequences, because they assume central role in family life. Functional, affective and relational movements occurring in the family with breast cancer diagnosis, seems to be frequent and with important implications, which has been little studied in our population. These aspects should be considered as an important element in the understanding and support given to Breast Cancer patients and their families. © Asociación de Psicooncología de Madrid