학술논문
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.
Document Type
Academic Journal
Author
Llera AS; Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.; Abdelhay ESFW; Bone Marrow Transplantation Unit, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.; Artagaveytia N; Hospital de Clínicas Manuel Quintela, Universidad de la República, Montevideo, Uruguay.; Daneri-Navarro A; Universidad de Guadalajara, Guadalajara, Mexico.; Müller B; Instituto Nacional del Cáncer, Santiago, Chile.; Velazquez C; Universidad de Sonora, Hermosillo, Mexico.; Alcoba EB; Hospital Municipal de Oncología María Curie, Buenos Aires, Argentina.; Alonso I; Centro Hospitalario Pereira Rossell, Montevideo, Uruguay.; Alves da Quinta DB; Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.; Universidad Argentina de la Empresa (UADE), Instituto de Tecnología (INTEC), Buenos Aires, Argentina.; Binato R; Bone Marrow Transplantation Unit, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.; Bravo AI; Hospital Regional de Agudos Eva Perón, San Martín, Argentina.; Camejo N; Hospital de Clínicas Manuel Quintela, Universidad de la República, Montevideo, Uruguay.; Carraro DM; Laboratory of Genomics and Molecular Biology/Centro Internacional de Pesquisa (CIPE), AC Camargo Cancer Center, Sao Paulo, Brazil.; Castro M; Instituto de Oncología Angel Roffo, Buenos Aires, Argentina.; Castro-Cervantes JM; Hospital de Especialidades CMNO-IMSS, Guadalajara, Mexico.; Cataldi S; Instituto Nacional del Cáncer, Montevideo, Uruguay.; Cayota A; Institut Pasteur de Montevideo, Montevideo, Uruguay.; Cerda M; Integrative Biology Program, Instituto de Ciencias Biomédicas (ICBM), Centro de Informática Médica y Telemedicina, Facultad de Medicina, Instituto de Neurociencias Biomédicas, Universidad de Chile, Santiago, Chile.; Colombo A; Department of Pathology, Facultad de Medicina y Hospital Clínico, Universidad de Chile, Santiago, Chile.; Crocamo S; Oncology Department, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.; Del Toro-Arreola A; Universidad de Guadalajara, Guadalajara, Mexico.; Delgadillo-Cisterna R; Hospital de Especialidades CMNO-IMSS, Guadalajara, Mexico.; Delgado L; Hospital de Clínicas Manuel Quintela, Universidad de la República, Montevideo, Uruguay.; Dreyer-Breitenbach M; Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.; Fejerman L; Department of Public Health Sciences and Comprehensive Cancer Center, University of California Davis, Davis, CA, United States.; Fernández EA; Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas [Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE) CONICET/Universidad Católica de Córdoba], Córdoba, Argentina.; Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina.; Fernández J; Instituto de Salud Pública, Santiago, Chile.; Fernández W; Hospital San Borja Arriarán, Santiago, Chile.; Franco-Topete RA; Organismo Público Descentralizado (OPD), Hospital Civil de Guadalajara, Universidad de Guadalajara, Guadalajara, Mexico.; Gabay C; Instituto de Oncología Angel Roffo, Buenos Aires, Argentina.; Gaete F; Hospital Luis Tisne, Santiago, Chile.; Garibay-Escobar A; Universidad de Sonora, Hermosillo, Mexico.; Gómez J; Texas A&M University, Houston, TX, United States.; Greif G; Institut Pasteur de Montevideo, Montevideo, Uruguay.; Gross TG; Center for Global Health, National Cancer Institute, Rockville, MD, United States.; Guerrero M; Hospital San José, Santiago, Chile.; Henderson MK; Center for Global Health, National Cancer Institute, Rockville, MD, United States.; Lopez-Muñoz ME; Universidad de Sonora, Hermosillo, Mexico.; Lopez-Vazquez A; Universidad de Sonora, Hermosillo, Mexico.; Maldonado S; Hospital Regional de Agudos Eva Perón, San Martín, Argentina.; Morán-Mendoza AJ; Hospital de Gineco-Obstetricia CMNO-IMSS, Guadalajara, Mexico.; Nagai MA; Center for Translational Research in Oncology, Cancer Institute of São Paulo (ICESP), Sao Paulo University Medical School, Sao Paulo, Brazil.; Oceguera-Villanueva A; Instituto Jalisciense de Cancerologia, Guadalajara, Mexico.; Ortiz-Martínez MA; Hospital General Regional No. 1, IMSS, Obregon, Mexico.; Quintero J; Universidad de Sonora, Cajeme, Mexico.; Quintero-Ramos A; Universidad de Guadalajara, Guadalajara, Mexico.; Reis RM; Molecular Oncology Research Center, Hospital de Câncer de Barretos, Barretos, Brazil.; Retamales J; Grupo Oncológico Cooperativo Chileno de Investigación, Santiago, Chile.; Rivera-Claisse E; Centro Estatal de Oncologia, Hermosillo, Mexico.; Rocha D; Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina.; Rodríguez R; Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay.; Rosales C; Hospital Municipal de Oncología María Curie, Buenos Aires, Argentina.; Salas-González E; Hospital de Gineco-Obstetricia CMNO-IMSS, Guadalajara, Mexico.; Sanchotena V; Hospital Municipal de Oncología María Curie, Buenos Aires, Argentina.; Segovia L; Hospital Barros Luco Trudeau, Santiago, Chile.; Sendoya JM; Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.; Silva-García AA; Organismo Público Descentralizado (OPD), Hospital Civil de Guadalajara, Universidad de Guadalajara, Guadalajara, Mexico.; Trinchero A; Hospital Regional de Agudos Eva Perón, San Martín, Argentina.; Valenzuela O; Universidad de Sonora, Hermosillo, Mexico.; Vedham V; Center for Global Health, National Cancer Institute, Rockville, MD, United States.; Zagame L; Instituto Jalisciense de Cancerologia, Guadalajara, Mexico.; Podhajcer OL; Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Source
Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2234-943X
Abstract
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).
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(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.)
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).
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(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.)