학술논문
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients
Document Type
article
Author
Andrea Sabina Llera; Eliana Saul Furquim Werneck Abdelhay; Nora Artagaveytia; Adrián Daneri-Navarro; Bettina Müller; Carlos Velazquez; Elsa B. Alcoba; Isabel Alonso; Daniela B. Alves da Quinta; Renata Binato; Alicia Inés Bravo; Natalia Camejo; Dirce Maria Carraro; Mónica Castro; Juan M. Castro-Cervantes; Sandra Cataldi; Alfonso Cayota; Mauricio Cerda; Alicia Colombo; Susanne Crocamo; Alicia Del Toro-Arreola; Raúl Delgadillo-Cisterna; Lucía Delgado; Marisa Dreyer-Breitenbach; Laura Fejerman; Elmer A. Fernández; Jorge Fernández; Wanda Fernández; Ramón A. Franco-Topete; Carolina Gabay; Fancy Gaete; Adriana Garibay-Escobar; Jorge Gómez; Gonzalo Greif; Thomas G. Gross; Marisol Guerrero; Marianne K. Henderson; Miguel E. Lopez-Muñoz; Alejandra Lopez-Vazquez; Silvina Maldonado; Andrés J. Morán-Mendoza; Maria Aparecida Nagai; Antonio Oceguera-Villanueva; Miguel A. Ortiz-Martínez; Jael Quintero; Antonio Quintero-Ramos; Rui M. Reis; Javier Retamales; Ernesto Rivera-Claisse; Darío Rocha; Robinson Rodríguez; Cristina Rosales; Efrain Salas-González; Verónica Sanchotena; Laura Segovia; Juan Martín Sendoya; Aida A. Silva-García; Alejandra Trinchero; Olivia Valenzuela; Vidya Vedham; Livia Zagame; United States-Latin American Cancer Research Network (US-LACRN); Osvaldo L. Podhajcer; Juan Abarca; Pamela Acevedo; Graciela Acosta; Gissel Acosta; Gabriela Acosta Haab; Ana Lilian Acosta Silva; Marta Aghazarian; Carola Aguayo; Bernardo Aizen; Gustavo Alarcon Lopez; Liz Almeida; Ana Alvarez; Viviane Andrade; Wenceslao Angeles-Bueno; Roberto Arai; Priscila Elvira Arambula Barreras; Ma. Isabel Aramburo Rubio; Gonzalo Ardao; Lilia A. Arellano-Jimenez; Claudia Arias; Ricardo Armisen; Mauricio Aspee; Rodrigo Assar; Itzel Reneé Astiazarán Rascón; Sebastian Astorga; Maxwell Aviles Rodriguez; Antônio Bailão Junior; Adolfo E. Barragan-Curiel; Adelfo Barragan-Ruiz; Fernanda Bermudez; Julia Bernachin; Wilfrido Bernal Herrera; Mara Bonet; Sarah Brnich; Claudio Bustamante; Miguel Angel Bustamante; Julio Bustos-Gomez; Felipe de J Bustos-Rodriguez; Janett Caballero Jasso; Angie Calfuman; Antonio Hugo José Froes Marques; Mónica Campos; Soledad Cano; Juan C. Canton-Romero; Ricardo Cappetta; Paulina Carmona; Fernando Carrizo; André Lopes Carvalho; Erika Carvallo; Julio Carzoglio; Monica Casalnuovo; Benedicta Caserta; Alvaro Castillo; César Castillo; Roger Chammas; Mario Alberto Chavez Zamudio; Loreto Chia; Elisa Chiarello; Daniela Chirico; Esther Cisneros-Quirarter; Minor Raul Cordero Bautista; Valeria Cornejo; Baldemar Corral Villegas; Andrés Cortés; Sandra Cortés; Laura Cortes-Sanabria; German Salvador Cortez Zamorano; Alejandro Corvalan; Adolfo Cruz; Alba d'Aurora; Sandra De la Fuente; Soledad De la Peña; Roberto de Leon Caballero; Mirian de Souza; César Del Castillo; Azucena Del-Toro-Valero; Mirtha Di Pretoro; Andrea Digonzelli; Jose El Ters; Paula Escobar; Marcela Estolaza; Adriane Feijo Evangelista; Marcelo Fanelli; Paulo Farias; Graciela Fernandez; José R. Filassi; Natalia Filgueiras; Diego Flaks; Edgar G. Flores-Ayala; Maria R. Flores-Marquez; David Franco Hughes; Karina Franco-Topete; Jimena Freire; Cristobal Fresno; Romina Gabrielli; Mario Gallegos; Jorge Gamboa; Daiana Ganiewich; Carlos Garbovesky; Ruben Alejandro Garcia Munguia; Ricardo Garcia-Gaeta; Alma C. Garcia-Martinez; Liliana Gimenez; Hector Gómez Silveira; Mariana M. Gomez-Del Toro; Marcela Gonzalez; Alicia Gonzalez; Germán González; Cesar Osbaldo Gonzalez Mondaca; Leivy P. Gonzalez-Ramirez; Beatriz Gonzalez-Ulloa; Susana Gorostidy; Mariela Grass; Alfonso G. Guevara Torres; Lorena Gutierrez; Susan A. Gutierrez-Rubio; Adrián Hannois; Andrew Hart; Steffen Härtel; Marcos Henriquez; Rafael Hernandez Guevara; Miriam E. Hernandez-Franco; Manuel I. Herrera-Miramontes; Graciela Horton; Gladys Ibañez; Martín Ipiña; Beatriz Jalfin; Lilian Jara; Raul Jara; Maria Luisa Jaramillo; David Javalera-Castro; Maria Eugenia Jimenez; Hugo Ju; Nazareth Juárez Rusjan; Karen Juneman; Ligia Maria Kerr; Alejandra Krupelis; Flor Esmeralda Larios-Jimenez; Jose Domingo Latorre; Guillermo Laviña; Fernando Lavista; Irma Leticia León Duarte; Alberto Lescano; Verónica Lezano; Rossana Mendoza Lopez; Jose Guillermo Lopez Cervantes; Miguel Enrique Lopez Muñoz; Dora Loria; Alejandra Luque; Alejandro Maass; Maria do Socorro Maciel; Flavia Rotea Mangone; Jorge Mansilla; Katherine Marcelain; Carolina Mariani; Marcia Maria Chiquitelli Marques; Reyna J. Martinez-Arriaga; Hector R. Martinez-Ramirez; Marcela Martins; Alma G. Maya-Gonzalez; Brenda Mazzaferri; Yadira Medina-Mora; Mariana Menini; Silvia Míguez; Soledad Milans; Soledad Montes; Ana Verónica Morales Hernández; Giberto Morga-Villela; Carla Morong; Homero Muñoz; Ignacio Miguel Muse; Carina Mussetti; Eduardo Mussetti; Luis J. Najar-Acosta; Elisa Napolitano e Ferreira; Nancy E. Navarro-Ruiz; Cristina Noblía; João Soares Nunes; Daniela Núñez; Fabiola Núñez; Nilton Onari; Emma M. Oropeza-De Anda; David Ortega Tirado; Cynthia Aparecida Bueno de Toledo Osório; Carlos Eduardo Paiva; Paulina Peñaloza; Miguel Peredo-Navarro; David Pereira; Laura Perez Michel; Francisca Pino; Tania Pino; Natalia Pinto; Jessica Pizarro; Carlos Pressa; Enrique Ramirez; Gladys E. Ramirez-Rosales; Claudia Ramis; Maritza Ramos-Ramirez; Adela Rascon Alcantar; Silvana Ravaglio; Francois Richard; Omar Rios Méndez; Ramón Enrique Robles Zepeda; Iara Santana Rocha; Natalia Rodriguez; Vilma Rodriguez; Maria Teresa Rodriguez; Diego Rodriguez-Gonzalez; Rosemeire A Roela; Ana M Romero-Gomez; Ana M Rosales-Sandoval; Omar V Rubio-Plascencia; Florencia Russo; Gaciela Sabini; Isabel Saffie; Helena Salina Dias; Brenda Guadalupe Samaniego Soto; Julio San Martino; Benito Sanchez-Llamas; Daniel Sat-Muñoz; Mariana Savignano; Cristovam Scapulatempo Neto; Max Mano Senna; Carolina Silva; Jaime Silvera; Isabele Small; Fernando Soares; Iberê Soares; Silvana Soares dos Santos; Evandro Sobrosa de Mello; José Antonio Sola; Irene Sorín; Alejandra Sosa; Anabella Sosa; Claudio Sosa; Sandra Soto; Cristiano de Pádua Souza; Lucía Spangenberg; Gustavo Steffanof; Florencia Straminsky; Mónica Tapia; Raziel O. Tapia-Llanos; Geronimo M. Tavares-Macias; Guillermo Temperley; Veronica Terzieff; Vicente Teti; Javier Tognarelli; Verónica Toledo; Paulina Toro; Roberto Torres; Mariana Torres-Palomares; Rogelio Troyo-San Roman; Hernan Urbano; Nicolas Vacca; Daniel Vaimberg; María Lourdes Valencia Peña; Maria Lujan Vaselevich; Jaime Vazquez-Nares; Ezequiel Velez-Gomez; Laura N. Venegas-Godinez; Patricia Vercelli; Ricardo Verdugo; René Aloisio da Costa Vieira; Marta Vilensky; María José Villarubias; Manuel Isaac Villegas Gómez; Stella Viña; Silvia Vornetti; Anapaula Hidemi Uema Watanabe; Carlos Zamorano; Luis Zapata; Zdenka Zlatar
Source
Frontiers in Oncology, Vol 12 (2022)
Subject
Language
English
ISSN
2234-943X
Abstract
PurposesMost 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 MethodsWe 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.ResultsPAM50 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.ConclusionsThis 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 RegistrationClinicalTrials.gov (Identifier: NCT02326857).