Closing the gap: prognostic and predictive biomarker validation for personalized care in a Latin American hormone-dependent breast cancer cohort.

BACKGROUND: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort. METHODS: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers. RESULTS: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively). CONCLUSION: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort.

IL10 promoter variants are associated with gene expression but they are not markers of susceptibility to acute coronary syndrome.

Interleukin-10 (IL-10) is an immunomodulatory cytokine that plays a pivotal role in the pathogenesis of acute coronary syndromes (ACS). Here, we evaluated the role of IL10 promoter variants as markers for ACS susceptibility in Western Mexican patients as well as its association with IL10 mRNA and IL-10 plasma levels. Three promoter variants (- 1082 A > G, - 819 T > C and - 592 A > C) were analyzed in 300 ACS patients and 300 control group (CG) individuals. IL10 relative gene expression was evaluated in peripheral blood mononuclear cells (PBMC) and IL-10 levels were quantified in plasma. The allelic, genotypic and haplotypic frequencies did not show significant differences between groups. ACS patients had sevenfold higher mRNA IL10 level compared to CG (p = 0.0013). Homozygous C/C carriers in both - 819 T > C and - 592 A > C variants had 0.4-fold higher IL10 mRNA expression than heterozygous and polymorphic allele homozygous genotypes (p = 0.0357) in ACS group. There were significant differences in plasma IL-10 levels in CG and ACS group (1.001 vs 1.777 pg/mL, p = 0.0051). The variants were not markers of susceptibility to ACS in Western Mexican individuals. ACS patients showed higher IL10 expression than CG individuals which could be mediated by - 819 T > C and - 592 A > C variants and pharmacotherapy.

Evaluación de cinco polimorfismos de genes trombofílicos en parejas con aborto habitual / Assessment of five thrombophilic genetic polymorphisms among couples with habitual abortion

Se han propuesto factores genéticos trombofílicos asociados con anormalidades obstétricas que implican la terminación temprana del embarazo. El propósito del estudio fue investigar la posible asociación de polimorfismos génicos trombofílicos con el aborto habitual (AH). Se analizaron muestras de dos grupos de personas que participaron voluntariamente en el estudio. El primero (n>100) consistió en mujeres atendidas en el Centro Médico de Occidente del Instituto Mexicano del Seguro Social y a sus parejas, por el antecedente reproductivo de por lo menos tres abortos idiopáticos (n>100). El grupo de referencia (n>200) lo formaron adultos sanos de ambos sexos residentes de Jalisco. El ADN se extrajo de una muestra de sangre periférica y se tipificaron, mediante PCR–RFLP o –SSP, los polimorfismos FII G20210A, FV G1691A, MTHFR C677T, ECA I/D y TNF G–308A. Las proporciones genotípicas en el grupo de referencia fueron similares a las predichas por la ley de Hardy–Weinberg y las comparaciones intergrupales alélicas, genotípicas y fenotípicas no mostraron diferencias significativas para ninguno de los polimorfismos estudiados. Estos resultados sugieren que los polimorfismos de los genes trombofílicos no representan un factor de riesgo para AH en nuestro medio.

An association between thrombophilic genes and obstetric conditions with early pregnancy termination has been previously proposed. In the present study we attempted to evaluate the possible association between thrombophilic genetic polymorphisms and habitual abortion (HA). Samples from two groups of volunteers were analyzed. The experimental group (n>100) was conformed by women attending the Centro Medico de Occidente, IMSS and their male couples, with a reproductive history ofat least three miscarriages. The reference group (n > 200) was composed by male and female healthy adults living in the state of Jalisco, Mexico. DNA was extracted from peripheral blood, and polymorphisms FII G20210A , FVG1691A, MTHFR C677T, ECA IID y TNF G-308A were typed by PCR-RFLP or -SSP. Genotype proportions in the reference group were in agreement with the HardyWeinberg expectations. Allele, genotype, and phenotype proportion inter-group comparisons did not show statistically significant differences. The present results could not demonstrate that thrombophilic polymorphisms constitute risk factors for HA in Jalisco.