The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients
- Autores
- Llera, Andrea Sabina; Abdelhay, Eliana Saul Furquim Werneck; Artagaveytia, Nora; Daneri Navarro, Adrián; Müller, Bettina; Velazquez, Carlos; Alcoba, Elsa B.; Alonso, Isabel; Alves Da Quinta, Daniela Belén; Binato, Renata; Bravo, Alicia Inés; Camejo, Natalia; Carraro, Dirce Maria; Castro, Mónica; Castro Cervantes, Juan M.; Cataldi, Sandra; Cayota, Alfonso; Cerda, Mauricio; Colombo, Alicia; Crocamo, Susanne; Del Toro Arreola, Alicia; Delgadillo Cisterna, Raúl; Delgado, Lucía; Fernandez, Elmer Andres; Fejerman, Laura; Trinchero, Alejandra; Valenzuela, Olivia; Vedham, Vidya; Zagame, Livia; Podhajcer, Osvaldo Luis
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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; Argentina
Fil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Cancer; Brasil
Fil: Artagaveytia, Nora. Universidad de la Republica; Uruguay
Fil: Daneri Navarro, Adrián. Universidad de Guadalajara; México
Fil: Müller, Bettina. Instituto Nacional del Cáncer; Chile
Fil: Velazquez, Carlos. Universidad de Sonora; México
Fil: Alcoba, Elsa B.. Hospital Maria Curie; Argentina
Fil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; Uruguay
Fil: 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; Argentina
Fil: Binato, Renata. Instituto Nacional de Cancer; Brasil
Fil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; Argentina
Fil: Camejo, Natalia. Universidad de la Republica; Uruguay
Fil: Carraro, Dirce Maria. Centro Internacional de Pesquisa; Brasil
Fil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Fil: Castro Cervantes, Juan M.. Umae Hospital de Especialidades Centro Medico Nacional Siglo XXI; México
Fil: Cataldi, Sandra. Instituto Nacional del Cáncer; Uruguay
Fil: Cayota, Alfonso. Instituto Pasteur de Montevideo; Uruguay
Fil: Cerda, Mauricio. Universidad de Chile; Chile
Fil: Colombo, Alicia. Universidad de Chile; Chile
Fil: Crocamo, Susanne. National Cancer Institute; Estados Unidos
Fil: Del Toro Arreola, Alicia. Universidad de Guadalajara; México
Fil: Delgadillo Cisterna, Raúl. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; México
Fil: Delgado, Lucía. Universidad de la Republica; Uruguay
Fil: 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; Argentina
Fil: Fejerman, Laura. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; Argentina
Fil: Valenzuela, Olivia. Universidad de Sonora; México
Fil: Vedham, Vidya. National Cancer Institute; Estados Unidos
Fil: Zagame, Livia. Instituto Jalisciense de Cancerología; México
Fil: 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; Argentina - Materia
-
BIOLOGICAL PATHWAYS
BREAST CANCER
LATIN AMERICA
PAM50 SUBTYPES
RISK OF RECURRENCE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/218483
Ver los metadatos del registro completo
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The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American PatientsLlera, Andrea SabinaAbdelhay, Eliana Saul Furquim WerneckArtagaveytia, NoraDaneri Navarro, AdriánMüller, BettinaVelazquez, CarlosAlcoba, Elsa B.Alonso, IsabelAlves Da Quinta, Daniela BelénBinato, RenataBravo, Alicia InésCamejo, NataliaCarraro, Dirce MariaCastro, MónicaCastro Cervantes, Juan M.Cataldi, SandraCayota, AlfonsoCerda, MauricioColombo, AliciaCrocamo, SusanneDel Toro Arreola, AliciaDelgadillo Cisterna, RaúlDelgado, LucíaFernandez, Elmer AndresFejerman, LauraTrinchero, AlejandraValenzuela, OliviaVedham, VidyaZagame, LiviaPodhajcer, Osvaldo LuisBIOLOGICAL PATHWAYSBREAST CANCERLATIN AMERICAPAM50 SUBTYPESRISK OF RECURRENCEhttps://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1Purposes: 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; ArgentinaFrontiers Media2022-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/218483Llera, Andrea Sabina; Abdelhay, Eliana Saul Furquim Werneck; Artagaveytia, Nora; Daneri Navarro, Adrián; Müller, Bettina; et al.; The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients; Frontiers Media; Frontiers in Oncology; 12; 835626; 3-2022; 1-212234-943XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2022.835626/fullinfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.835626/fullinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:36:00Zoai:ri.conicet.gov.ar:11336/218483instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:36:00.958CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| title |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| spellingShingle |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients Llera, Andrea Sabina BIOLOGICAL PATHWAYS BREAST CANCER LATIN AMERICA PAM50 SUBTYPES RISK OF RECURRENCE |
| title_short |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| title_full |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| title_fullStr |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| title_full_unstemmed |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| title_sort |
The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients |
| dc.creator.none.fl_str_mv |
Llera, Andrea Sabina Abdelhay, Eliana Saul Furquim Werneck Artagaveytia, Nora Daneri Navarro, Adrián Müller, Bettina Velazquez, Carlos Alcoba, Elsa B. Alonso, Isabel Alves Da Quinta, Daniela Belén Binato, Renata Bravo, Alicia Inés Camejo, Natalia Carraro, Dirce Maria Castro, Mónica Castro Cervantes, Juan M. Cataldi, Sandra Cayota, Alfonso Cerda, Mauricio Colombo, Alicia Crocamo, Susanne Del Toro Arreola, Alicia Delgadillo Cisterna, Raúl Delgado, Lucía Fernandez, Elmer Andres Fejerman, Laura Trinchero, Alejandra Valenzuela, Olivia Vedham, Vidya Zagame, Livia Podhajcer, Osvaldo Luis |
| author |
Llera, Andrea Sabina |
| author_facet |
Llera, Andrea Sabina Abdelhay, Eliana Saul Furquim Werneck Artagaveytia, Nora Daneri Navarro, Adrián Müller, Bettina Velazquez, Carlos Alcoba, Elsa B. Alonso, Isabel Alves Da Quinta, Daniela Belén Binato, Renata Bravo, Alicia Inés Camejo, Natalia Carraro, Dirce Maria Castro, Mónica Castro Cervantes, Juan M. Cataldi, Sandra Cayota, Alfonso Cerda, Mauricio Colombo, Alicia Crocamo, Susanne Del Toro Arreola, Alicia Delgadillo Cisterna, Raúl Delgado, Lucía Fernandez, Elmer Andres Fejerman, Laura Trinchero, Alejandra Valenzuela, Olivia Vedham, Vidya Zagame, Livia Podhajcer, Osvaldo Luis |
| author_role |
author |
| author2 |
Abdelhay, Eliana Saul Furquim Werneck Artagaveytia, Nora Daneri Navarro, Adrián Müller, Bettina Velazquez, Carlos Alcoba, Elsa B. Alonso, Isabel Alves Da Quinta, Daniela Belén Binato, Renata Bravo, Alicia Inés Camejo, Natalia Carraro, Dirce Maria Castro, Mónica Castro Cervantes, Juan M. Cataldi, Sandra Cayota, Alfonso Cerda, Mauricio Colombo, Alicia Crocamo, Susanne Del Toro Arreola, Alicia Delgadillo Cisterna, Raúl Delgado, Lucía Fernandez, Elmer Andres Fejerman, Laura Trinchero, Alejandra Valenzuela, Olivia Vedham, Vidya Zagame, Livia Podhajcer, Osvaldo Luis |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
BIOLOGICAL PATHWAYS BREAST CANCER LATIN AMERICA PAM50 SUBTYPES RISK OF RECURRENCE |
| topic |
BIOLOGICAL PATHWAYS BREAST CANCER LATIN AMERICA PAM50 SUBTYPES RISK OF RECURRENCE |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.2 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
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; Argentina Fil: Abdelhay, Eliana Saul Furquim Werneck. Instituto Nacional de Cancer; Brasil Fil: Artagaveytia, Nora. Universidad de la Republica; Uruguay Fil: Daneri Navarro, Adrián. Universidad de Guadalajara; México Fil: Müller, Bettina. Instituto Nacional del Cáncer; Chile Fil: Velazquez, Carlos. Universidad de Sonora; México Fil: Alcoba, Elsa B.. Hospital Maria Curie; Argentina Fil: Alonso, Isabel. Centro Hospitalario Pereira Rossell; Uruguay Fil: 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; Argentina Fil: Binato, Renata. Instituto Nacional de Cancer; Brasil Fil: Bravo, Alicia Inés. Hospital Regional de Agudos Eva Perón; Argentina Fil: Camejo, Natalia. Universidad de la Republica; Uruguay Fil: Carraro, Dirce Maria. Centro Internacional de Pesquisa; Brasil Fil: Castro, Mónica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina Fil: Castro Cervantes, Juan M.. Umae Hospital de Especialidades Centro Medico Nacional Siglo XXI; México Fil: Cataldi, Sandra. Instituto Nacional del Cáncer; Uruguay Fil: Cayota, Alfonso. Instituto Pasteur de Montevideo; Uruguay Fil: Cerda, Mauricio. Universidad de Chile; Chile Fil: Colombo, Alicia. Universidad de Chile; Chile Fil: Crocamo, Susanne. National Cancer Institute; Estados Unidos Fil: Del Toro Arreola, Alicia. Universidad de Guadalajara; México Fil: Delgadillo Cisterna, Raúl. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; México Fil: Delgado, Lucía. Universidad de la Republica; Uruguay Fil: 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; Argentina Fil: Fejerman, Laura. University of California at Davis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Trinchero, Alejandra. Hospital Regional de Agudos Eva Perón; Argentina Fil: Valenzuela, Olivia. Universidad de Sonora; México Fil: Vedham, Vidya. National Cancer Institute; Estados Unidos Fil: Zagame, Livia. Instituto Jalisciense de Cancerología; México Fil: 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; Argentina |
| description |
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). |
| publishDate |
2022 |
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2022-03 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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http://hdl.handle.net/11336/218483 Llera, Andrea Sabina; Abdelhay, Eliana Saul Furquim Werneck; Artagaveytia, Nora; Daneri Navarro, Adrián; Müller, Bettina; et al.; The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients; Frontiers Media; Frontiers in Oncology; 12; 835626; 3-2022; 1-21 2234-943X CONICET Digital CONICET |
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http://hdl.handle.net/11336/218483 |
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Llera, Andrea Sabina; Abdelhay, Eliana Saul Furquim Werneck; Artagaveytia, Nora; Daneri Navarro, Adrián; Müller, Bettina; et al.; The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients; Frontiers Media; Frontiers in Oncology; 12; 835626; 3-2022; 1-21 2234-943X CONICET Digital CONICET |
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eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.3389/fonc.2022.835626/full info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.835626/full |
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| repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
| repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
| _version_ |
1844614379953192960 |
| score |
13.070432 |