The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients
Authors: 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 B. , 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 , Dreyer-Breitenbach Marisa , Fejerman Laura , Fernández Elmer A. , Fernández Jorge , 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 Silvina , Morán-Mendoza Andrés 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 , Rodríguez Robinson , Rosales Cristina , Salas-González Efrain , Sanchotena Verónica , Segovia Laura , Sendoya Juan Martín , Silva-García Aida A. , Trinchero Alejandra , Valenzuela Olivia , Vedham Vidya , Zagame Livia ,   United States-Latin American Cancer Research Network (US-LACRN), Podhajcer Osvaldo L. 
Published: March 2022

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).