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

dc.creatorLlera, Andrea Sabina
dc.creatorAbdelhay, Eliana
dc.creatorArtagaveytia, Nora
dc.creatorDaneri-Navarro, Adrian
dc.creatorMüller, Bettina
dc.creatorVelazquez, Carlos
dc.creatorAlcoba, Elsa
dc.creatorAlonso, Isabel
dc.creatorAlves da Quinta, Daniela B.
dc.creatorBinato, Renata
dc.creatorBravo, Alicia I.
dc.creatorCamejo, Natalia
dc.creatorCarraro, Dirce María
dc.creatorCastro, Mónica
dc.creatorCastro-Cervantes, Juan M.
dc.creatorCataldi, Sandra
dc.creatorCayota, Alfonso
dc.creatorCerda, Mauricio
dc.creatorColombo, Alicia
dc.creatorCrocamo, Susanne
dc.creatorDel Toro-Arreola, Alicia
dc.creatorDelgadillo-Cisterna, Raúl
dc.creatorDelgado, Lucía
dc.creatorDreyer-Breitenbach, Marisa
dc.creatorFejerman, Laura
dc.creatorFernández, Elmer Andrés
dc.creatorFernández, Wanda
dc.creatorFranco-Topete, Ramón A.
dc.creatorGabay, Carolina
dc.creatorGaete, Fancy
dc.creatorGaribay-Escobar, Adriana
dc.creatorGómez, Jorge
dc.creatorGreif, Gonzalo
dc.creatorGross, Thomas G.
dc.creatorGuerrero, Marisol
dc.creatorHenderson, Marianne K.
dc.creatorLopez-Muñoz, Miguel E.
dc.creatorLopez-Vazquez, Alejandra
dc.creatorMaldonado, Silvia
dc.creatorMoran-Mendoza, Andrés de J.
dc.creatorNagai, Maria Aparecida
dc.creatorOceguera-Villanueva, Antonio
dc.creatorOrtiz-Martínez, Miguel A.
dc.creatorQuintero, Jael
dc.creatorQuintero-Ramos, Antonio
dc.creatorReis, Rui M.
dc.creatorRetamales, Javier
dc.creatorRivera-Claisse, Ernesto
dc.creatorRocha, Darío
dc.creatorRodriguez, Robinson
dc.creatorRosales, Cristina
dc.creatorSalas-Gonzalez, Efrain
dc.creatorSanchotena, Verónica
dc.creatorSegovia, Laura
dc.creatorSendoya, Juan M.
dc.creatorSilva-Garcia, Aida A.
dc.creatorTrinchero, Alejandra
dc.creatorValenzuela, Olivia
dc.creatorVedham, Vidya
dc.date2022-03-22
dc.identifierhttp://pa.bibdigital.ucc.edu.ar/3295/1/A_Llera_Abdelhay_Artagaveytia.pdf
dc.descriptionPurposes: 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). Copyright © 2022 Llera, Abdelhay, Artagaveytia, Daneri-Navarro, Müller, Velazquez, Alcoba, Alonso, Alves da Quinta, Binato, Bravo, Camejo, Carraro, Castro, Castro-Cervantes, Cataldi, Cayota, Cerda, Colombo, Crocamo, Del Toro-Arreola, Delgadillo-Cisterna, Delgado, Dreyer-Breitenbach, Fejerman, Fernández, Fernández, Fernández, Franco-Topete, Gabay, Gaete, Garibay-Escobar, Gómez, Greif, Gross, Guerrero, Henderson, Lopez-Muñoz, Lopez-Vazquez, Maldonado, Morán-Mendoza, Nagai, Oceguera-Villanueva, Ortiz-Martínez, Quintero, Quintero-Ramos, Reis, Retamales, Rivera-Claisse, Rocha, Rodríguez, Rosales, Salas-González, Sanchotena, Segovia, Sendoya, Silva-García, Trinchero, Valenzuela, Vedham, Zagame, United States-Latin American Cancer Research Network (US-LACRN) and Podhajcer.
dc.descriptionFil: Llera, Andrea Sabina. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; Argentina
dc.descriptionFil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Câncer. Bone Marrow Transplantation Unit; Brasil
dc.descriptionFil: Artagaveytia, Nora. Universidad de la República. Hospital de Clínicas Manuel Quintela; Uruguay
dc.descriptionFil: Daneri-Navarro, Adrián. Universidad de Guadalajara; México
dc.descriptionFil: Müller, Bettina. Instituto Nacional del Cáncer; Chile
dc.descriptionFil: Velazquez, Carlos. Universidad de Sonora; México
dc.descriptionFil: Alcoba, Elsa B. Hospital Municipal de Oncología María Curie; Argentina
dc.descriptionFil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; Uruguay
dc.descriptionFil: Alves da Quinta, Daniela B. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; Argentina
dc.descriptionFil: Alves da Quinta, Daniela B. Universidad Argentina de la Empresa (UADE). Instituto de Tecnología (INTEC); Argentina
dc.descriptionFil: Binato, Renata. Instituto Nacional de Câncer. Bone Marrow Transplantation Unit; Brasil
dc.descriptionFil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; Argentina
dc.descriptionFil: Camejo, Natalia. Universidad de la República. Hospital de Clínicas Manuel Quintela; Uruguay
dc.descriptionFil: Carraro, Dirce Maria. AC Camargo Cancer Center. Centro Internacional de Pesquisa (CIPE). Laboratory of Genomics and Molecular Biology; Brasil
dc.descriptionFil: Castro, Mónica. Instituto de Oncología Angel Roffo; Argentina
dc.descriptionFil: Castro-Cervantes, Juan M. Hospital de Especialidades CMNO-IMSS; México
dc.descriptionFil: Cataldi, Sandra. Instituto Nacional del Cáncer; Uruguay
dc.descriptionFil: Cayota, Alfonso. Institut Pasteur de Montevideo; Uruguay
dc.descriptionFil: Cerda, Mauricio. Universidad de Chile. Instituto de Neurociencias Biomédicas. Facultad de Medicina. Centro de Informática Médica y Telemedicina. Instituto de Ciencias Biomédicas (ICBM). Integrative Biology Program; Chile
dc.descriptionFil: Colombo, Alicia. Universidad de Chile. Facultad de Medicina y Hospital Clínico. Department of Pathology; Chile
dc.descriptionFil: Crocamo, Susanne. Instituto Nacional de Câncer. Oncology Department; Brasil
dc.descriptionFil: Del Toro-Arreola, Alicia. Universidad de Guadalajara; México
dc.descriptionFil: Delgadillo-Cisterna, Raúl. Hospital de Especialidades CMNO-IMSS; México
dc.descriptionFil: Delgado, Lucía. Universidad de la República. Hospital de Clínicas Manuel Quintela; Uruguay
dc.descriptionFil: Dreyer-Breitenbach, Marisa. Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcantara Gomes; Brasil
dc.descriptionFil: Fejerman, Laura. University of California Davis. Department of Public Health Sciences and Comprehensive Cancer Center; Estados Unidos
dc.descriptionFil: Fernández, Elmer A. Universidad Católica de Córdoba. CONICET. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas [Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE); Argentina
dc.descriptionFil: Fernández, Elmer A. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina
dc.descriptionFil: Fernández, Wanda. Hospital San Borja Arriarán; Chile
dc.descriptionFil: Franco-Topete, Ramón A. Universidad de Guadalajara. Hospital Civil de Guadalajara. Organismo Público Descentralizado (OPD); México
dc.descriptionFil: Gabay, Carolina. Instituto de Oncología Angel Roffo; Argentina
dc.descriptionFil: Gaete, Fancy. Hospital Luis Tisne; Chile
dc.descriptionFil: Garibay-Escobar, Adriana. Universidad de Sonora; México
dc.descriptionFil: Gómez, Jorge. Texas A&M University; Estados Unidos
dc.descriptionFil: Greif, Gonzalo. Institut Pasteur de Montevideo; Uruguay
dc.descriptionFil: Gross, Thomas G. Center for Global Health, National Cancer Institute; Estados Unidos
dc.descriptionFil: Guerrero, Marisol. Hospital San José; Chile
dc.descriptionFil: Henderson, Marianne K. Center for Global Health, National Cancer Institute; Estados Unidos
dc.descriptionFil: Lopez-Muñoz, Miguel E. Universidad de Sonora; México
dc.descriptionFil: Lopez-Vazquez, Alejandra. Universidad de Sonora; México
dc.descriptionFil: Maldonado, Silvina. Hospital Regional de Agudos Eva Perón; Argentina
dc.descriptionFil: Morán-Mendoza, Andrés J. Hospital de Gineco-Obstetricia CMNO-IMSS; México
dc.descriptionFil: Nagai, Maria Aparecida. Sao Paulo University Medical School. Cancer Institute of São Paulo (ICESP). Center for Translational Research in Oncology; Brasil
dc.descriptionFil: Oceguera-Villanueva, Antonio. Instituto Jalisciense de Cancerologia; México
dc.descriptionFil: Ortiz-Martínez, Miguel A. Hospital General Regional No. 1. IMSS; México
dc.descriptionFil: Quintero, Jael. Universidad de Sonora; México
dc.descriptionFil: Quintero-Ramos, Antonio. Universidad de Guadalajara; México
dc.descriptionFil: Reis, Rui M. Hospital de Câncer de Barretos. Molecular Oncology Research Center; Brasil
dc.descriptionFil: Retamales, Javier. Grupo Oncológico Cooperativo Chileno de Investigación; Chile
dc.descriptionFil: Rivera-Claisse, Ernesto. Centro Estatal de Oncologia; México
dc.descriptionFil: Rocha, Darío. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina
dc.descriptionFil: Rodríguez, Robinson. Hospital Central de las Fuerzas Armadas; Uruguay
dc.descriptionFil: Rosales, Cristina. Hospital Municipal de Oncología María Curie; Argentina
dc.descriptionFil: Salas-González, Efrain. Hospital de Gineco-Obstetricia CMNO-IMSS; México
dc.descriptionFil: Sanchotena, Verónica. Hospital Municipal de Oncología María Curie; Argentina
dc.descriptionFil: Segovia, Laura. Hospital Barros Luco Trudeau; Chile
dc.descriptionFil: Sendoya, Juan Martín. Fundación Instituto Leloir-CONICET. Molecular and Cellular Therapy Laboratory; Argentina
dc.descriptionFil: Silva-García, Aida A. Universidad de Guadalajara. Hospital Civil de Guadalajara. Organismo Público Descentralizado (OPD); México
dc.descriptionFil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; Argentina
dc.descriptionFil: Valenzuela, Olivia. Universidad de Sonora; México
dc.descriptionFil: Vedham, Vidya. National Cancer Institute. Center for Global Health; Estados Unidos
dc.formatapplication/pdf
dc.languagespa
dc.publisherFrontiers Media S.A.
dc.relationhttp://pa.bibdigital.ucc.edu.ar/3295/
dc.relationhttps://www.frontiersin.org/articles/10.3389/fonc.2022.835626/full
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.3389/fonc.2022.835626
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.sourceLlera, Andrea Sabina ORCID: https://orcid.org/0000-0002-0089-0061 <https://orcid.org/0000-0002-0089-0061>, Abdelhay, Eliana, Artagaveytia, Nora, Daneri-Navarro, Adrian, Müller, Bettina, Velazquez, Carlos, Alcoba, Elsa, Alonso, Isabel, Alves da Quinta, Daniela B., Binato, Renata, Bravo, Alicia I., Camejo, Natalia, Carraro, Dirce María, Castro, Mónica, Castro-Cervantes, Juan M., Cataldi, Sandra, Cayota, Alfonso, Cerda, Mauricio ORCID: https://orcid.org/0000-0003-3447-1815 <https://orcid.org/0000-0003-3447-1815>, Colombo, Alicia, Crocamo, Susanne, Del Toro-Arreola, Alicia ORCID: https://orcid.org/0000-0002-1994-9027 <https://orcid.org/0000-0002-1994-9027>, Delgadillo-Cisterna, Raúl, Delgado, Lucía, Dreyer-Breitenbach, Marisa, Fejerman, Laura, Fernández, Elmer Andrés ORCID: https://orcid.org/0000-0002-4711-8634 <https://orcid.org/0000-0002-4711-8634>, Fernández, Wanda, Franco-Topete, Ramón A., Gabay, Carolina, Gaete, Fancy, Garibay-Escobar, Adriana, Gómez, Jorge, Greif, Gonzalo, Gross, Thomas G., Guerrero, Marisol, Henderson, Marianne K., Lopez-Muñoz, Miguel E., Lopez-Vazquez, Alejandra, Maldonado, Silvia, Moran-Mendoza, Andrés de J., Nagai, Maria Aparecida, Oceguera-Villanueva, Antonio, Ortiz-Martínez, Miguel A., Quintero, Jael, Quintero-Ramos, Antonio, Reis, Rui M., Retamales, Javier, Rivera-Claisse, Ernesto, Rocha, Darío, Rodriguez, Robinson, Rosales, Cristina, Salas-Gonzalez, Efrain, Sanchotena, Verónica, Segovia, Laura, Sendoya, Juan M., Silva-Garcia, Aida A., Trinchero, Alejandra, Valenzuela, Olivia ORCID: https://orcid.org/0000-0002-4456-2107 <https://orcid.org/0000-0002-4456-2107> and Vedham, Vidya (2022) The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients. Frontiers in Oncology, 12. ISSN 2234-943X
dc.subjectR Medicina (General)
dc.subjectRC0254 Neoplasias. Los tumores. Oncología (incluyendo cáncer)
dc.titleThe Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo


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