Translational cancer research comes of age in Latin America

Llera, Andrea S.; Podhajcer, Osvaldo L.; Breitenbach, M; Santini, Luiz Antônio; Müller, Bettina; Daneri-Navarro, ́Adrián; Velázquez, Carlos; Artagaveytia, Nora; Gómez, J. M. García; Frech, M. Silvina; Brown, Trissia; Gross, Thomas G.

doi:10.1126/scitranslmed.aad5859

Cited by 12 publications

(7 citation statements)

References 9 publications

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“…This paper reports the first epidemiological and molecular analysis of a study carried out by the LACRN in collaboration with the National Cancer Institute/USA. The general objective of this network is to strengthen collaborative research efforts among the participating countries, advance translational cancer research, and serve as a basis for planning new actions to reduce the global cancer burden, focusing on breast cancer as a priority ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…Using standardized questionnaire, trained interviewers collected epidemiological data. In addition to molecular profiling of tumor tissue described in an earlier publication ( 14 ), clinical data were collected from medical records. Women were followed up through death from any cause for 5 years ( Supplementary Figure S2 ).…”

Section: Methodsmentioning

confidence: 99%

“…To better understand the characteristics and survival of Latin American women with breast cancer, epidemiologists from Argentina, Brazil, Chile, Mexico, Uruguay, and the USA conducted the Molecular Profiling of Stage II and III Breast Cancer in Latin American Women Receiving Standard-of-Care Treatment (MPBC) study, proposed by the US-Latin America Cancer Research Network (US-LACRN) ( 14 ). The goal of this study was to describe the characteristics of the Latin American women with breast cancer by country and to identify predictors for 60-month cumulative probability of overall survival.…”

Section: Introductionmentioning

confidence: 99%

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Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

et al. 2022

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Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher’s exact tests and the OS by Kaplan–Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

et al. 2022

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“…Additionally, we compared the enriched molecular pathways in MPBCS subtypes with those found in the TCGA selected cohort of stage II-III breast cancer patients. This initiative of the United States-Latin America Cancer Research Network (US-LACRN, or LACRN), launched by the Center for Global Health of the US-National Cancer Institute, NIH, USA, and institutions of Argentina, Brazil, Chile, Mexico and Uruguay, focused on the integrative profiling of stage II-III breast cancer in Latin American women ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

et al. 2022

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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).

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“…There are ongoing efforts to improve homogeneity of study design and increase sample size in studies in Latin America. In 2009, the Center for Global Health of the US National Cancer Institute (NCI) created the US-Latin America Cancer Research Network (LACRN), a collaborative management structure that includes Argentina, Brazil, Chile, Mexico, and Uruguay [207]. In 2011 the US–LACRN launched the “Molecular Profiling of Stage II and III Breast Cancer in Latin American Women Receiving Standard of Care Treatment (MPBC)” study.…”

Section: Discussionmentioning

confidence: 99%

Genetic Epidemiology of Breast Cancer in Latin America

Zavala

Serrano-Gómez

Dutil

et al. 2019

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The last 10 years witnessed an acceleration of our understanding of what genetic factors underpin the risk of breast cancer. Rare high- and moderate-penetrance variants such as those in the BRCA genes account for a small proportion of the familial risk of breast cancer. Low-penetrance alleles are expected to underlie the remaining heritability. By now, there are about 180 genetic polymorphisms that are associated with risk, most of them of modest effect. In combination, they can be used to identify women at the lowest or highest ends of the risk spectrum, which might lead to more efficient cancer prevention strategies. Most of these variants were discovered in populations of European descent. As a result, we might be failing to discover additional polymorphisms that could explain risk in other groups. This review highlights breast cancer genetic epidemiology studies conducted in Latin America, and summarizes the information that they provide, with special attention to similarities and differences with studies in other populations. It includes studies of common variants, as well as moderate- and high-penetrance variants. In addition, it addresses the gaps that need to be bridged in order to better understand breast cancer genetic risk in Latin America.

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Translational cancer research comes of age in Latin America

Abstract: The U.S.–Latin America Cancer Research Network strives to expand translational research capabilities and forge new collaborations.

Cited by 12 publications

References 9 publications

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients

Genetic Epidemiology of Breast Cancer in Latin America

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