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, Podhajcer Osvaldo L
Molecular and Cellular Therapy Laboratory, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Bone Marrow Transplantation Unit, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Front Oncol. 2022 Mar 22;12:835626. doi: 10.3389/fonc.2022.835626. eCollection 2022.
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.
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.
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.
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.
ClinicalTrials.gov (Identifier: NCT02326857).
大多数已发表的基于分子的乳腺癌研究未能充分体现拉丁美洲人群独特且多样的基因混合情况。探寻与这些肿瘤相关的分子通路中的异同，并评估其对预后的影响，可能有助于选择更好的治疗方法。
我们收集了乳腺癌分子图谱研究（MPBCS）队列中1071例II - III期乳腺癌患者的多国拉丁美洲队列的临床、病理和转录组数据。比较了内在（基于转录组）PAM50分类和免疫组化分类在癌症特异性（OSC）和无病生存期（DFS）阶段的5年预后能力。进行了通路分析（GSEA、GSVA和MetaCore）以探索内在亚型之间的差异。
MPBCS队列的PAM50分类将42.6%的肿瘤定义为LumA，21.3%为LumB，13.3%为HER2E，16.6%为基底型。LumA肿瘤的OSC和DFS均显著优于其他亚型，而基底型肿瘤预后最差。虽然通过激素受体（HR）、HER2和Ki67测定计算的传统亚型的预后能力表现尚可，但PAM50衍生的复发风险能最好地区分低、中、高危组。转录组通路分析显示，LumB、HER2E和基底型肿瘤与高增殖（即细胞周期控制和DNA损伤修复）相关，而LumA对雌激素通路有强烈依赖性。与固有免疫和适应性免疫反应相关的术语在基底型肿瘤中主要上调，在HER2E中上调程度较小，而在LumA和LumB肿瘤中则不然。
这是第一项在多国拉丁美洲乳腺癌患者队列中评估转录组水平分子特征的研究。在PAM50和其他乳腺癌分子分类中占主导的激素相关和增殖通路也是该队列中的主要肿瘤驱动机制，并且具有预后能力。在最具侵袭性的亚型中看到的免疫相关特征可能为拉丁美洲尚未普及的治疗方法铺平道路。
ClinicalTrials.gov（标识符：NCT02326857）。
