Supervivencia a 5 años de pacientes con cáncer de mama: experiencia en una institución de Jalisco, México / Breast cancer survival at 5 years: Experience of an institution at Jalisco, México

Resumen: OBJETIVO: Determinar la supervivencia a 5 años (global y libre de enfermedad) posterior al tratamiento de pacientes con cáncer de mama atendidas en el Instituto Jalisciense de Cancerología. MATERIALES Y MÉTODOS: Estudio observacional, descriptivo, transversal y retrospectivo efectuado en pacientes con diagnóstico de cáncer de mama atendidas en el trascurso del año 2013 en la Clínica de Mama del Instituto Jalisciense de Cancerología, Guadalajara. La supervivencia global y libre de enfermedad a 5 años se estableció a partir del tiempo trascurrido desde el diagnóstico hasta la ocurrencia de recidiva, metástasis, muerte o fecha del último contacto, con límite a diciembre de 2018. RESULTADOS: Se revisaron 311 expedientes pero solo se analizaron 172. La edad promedio al diagnóstico fue de 51.4 años. La etapa más repetida fue la IIIA, determinada en 64 pacientes (37.2%), IIA en 38 pacientes (22.1%), IIB en 19 pacientes (11.0%), IA y IIIC cada una con 15 pacientes (8.7%). La probabilidad de supervivencia global a cinco años fue de 78.5%. El 24.4% tuvo recurrencia, con una media de supervivencia de 46.8 meses. Se demostró significación estadística entre la etapa, grado histológico, reporte inmunohistoquímico e invasión ganglionar y la supervivencia. CONCLUSIONES: Esta investigación representa un esfuerzo para lograr establecer la supervivencia a cinco años de nuestras pacientes. En la población estudiada, la supervivencia tuvo valores aceptables y equiparables con otros estudios nacionales e internacionales y refleja la buena práctica médica de nuestra institución.

Abstract: OBJECTIVE: To determine the 5-year survival (global and disease-free) after the treatment of patients with breast cancer at the Instituto Jalisciense de Cancerología. MATERIALS AND METHODS: Observational, descriptive cross-sectional, retrospective study of patients diagnosed with breast cancer treated during 2013 in the breast clinic service of the Instituto Jalisciense de Cancerología, Guadalajara. The five-year global and disease-free survival was established from the time elapsed from the diagnosis until the occurrence of an event (recurrence, metastasis or death) or date of last contact, with a limit to December 2018. RESULT: 311 files were reviewed, but only 172 were included for the analysis of overall survival and disease-free survival at five years. The average age at diagnosis was 51.4 years. The most repeated stage was IIIA, determined in 64 patients (37.4%), IIA in 38 patients (22.2%), IIB in 19 patients (11.1%), AI and IIIC each with 15 patients (8.8%). The probability of five-year global survival was 78.5%. 24.4% presented recurrence with an average survival of 46.8 months. Statistical significance was demonstrated between stage, histological grade, result of immunohistochemistry and lymph node invasion and survival. CONCLUSIONS: This research represents an effort to establish the five-year survival of our patients. In the population studied, survival had acceptable and comparable values with other national and international studies and reflects the good medical practice of our institution.

MIF mRNA Expression and Soluble Levels in Acute Coronary Syndrome.

Acute coronary syndrome (ACS) describes any condition characterized by myocardial ischaemia and reduction in blood flow. The physiopathological process of ACS is the atherosclerosis where MIF operates as a major regulator of inflammation. The aim of this study was to assess the mRNA expression of MIF gene and its serum levels in the clinical manifestations of ACS and unrelated individuals age- and sex-matched with patients as the control group (CG). All samples were run using the conditions indicated in TaqMan Gene Expression Assay protocol. Determination of MIF serum levels were performed by enzyme-linked immunosorbent assay and MIF ELISA Kit. ST-segment elevation myocardial infraction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) showed 0.8 and 0.88, respectively, less expression of MIF mRNA with regard to CG. UA and STEMI presented more expression than NSTEMI 5.23 and 0.68, respectively. Otherwise, ACS patients showed significant higher MIF serum levels (p=0.02) compared with CG. Furthermore, the highest soluble levels of MIF were presented by STEMI (11.21 ng/dL), followed by UA (10.34 ng/dL) and finally NSTEMI patients (8.75 ng/dL); however, the differences were not significant. These novel observations further establish the process of MIF release after cardiovascular events and could support the idea of MIF as a new cardiac biomarker in ACS.

Association of the -1031T>C polymorphism and soluble TNF-α levels with Acute Coronary Syndrome.

INTRODUCTION: Inflammation has gained a pivotal role in the pathophysiology of Acute Coronary Syndrome (ACS). TNF-α is a pro-inflammatory cytokine that could be a potential biomarker in ACS due to its multiple functions. The rs1799964 TNFA polymorphism (-1031T>C) has been associated with a decrease in gene transcription and cytokine levels. OBJECTIVE: To determine the association of rs1799964 TNFA polymorphism and TNF-α soluble levels in ACS. METHODS: A total of 251 patients diagnosed with ACS and 164 individuals without cardiovascular diseases classified as the reference group (RG), were included. The rs1799964 polymorphism was genotyped by PCR-RFLP. Soluble protein levels were determined by ELISA. Statistical analyses were performed using chi square and U-Mann Whitney tests. RESULTS: The genotype and allele frequencies were different between ACS and RG (OR=0.317, p=0.01; OR=0.688, p=0.03 respectively). ACS patients had higher soluble TNF-α levels compared with the RG (31.08 vs 23.00pg/mL, p<0.001); according genotype significant differences were observed (T/T: 24.06 vs T/C: 34.95pg/mL, p=0.0001) in patients. In the RG, T/T carriers showed discrete lower levels than C/C genotype (22.14 vs 27.83pg/mL, p=0.04). CONCLUSIONS: The -1031C allele of the TNFA polymorphism confers protection for the development of ACS. The T/C genotype carriers had higher TNF-α serum levels compared to the T/T genotype in ACS. In addition, the -1031T>C TNFA polymorphism was associated with dyslipidemia in ACS in a Western Mexican population.

The -844 G>A PAI-1 polymorphism is associated with acute coronary syndrome in Mexican population.

BACKGROUND: Acute coronary syndrome (ACS) has an important impact in public health with high morbidity and mortality. Prothrombotic and proinflammatory states are involved in the pathogenesis of the disease. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of the fibrinolysis and also is part of immune response. The -844 G>A gene polymorphism is related to increased PAI-1 protein levels. The aim of the study is to evaluate the association of -844 G>A PAI-1 polymorphism with ACS. METHODS: A total of 646 individuals were recruited from Western Mexico: 350 unrelated healthy subjects and 296 patients with diagnosis of ACS. RESULTS: The most important risk factor in our population was hypertension, followed by smoking. The genetic distribution showed an association of the A allele (OR = 1.27, P = 0.04) and AA genotype (OR = 1.86, P = 0.02) with ACS. The recessive model displayed similar results (OR = 1.76, P = 0.02). As additional finding, we observed significant differences in the genetic distribution of ACS dyslipidemic patients (OR = 1.99, P = 0.04). The A allele and AA genotype of -844 polymorphism of PAI-1 gene are risk factors for ACS. The AA genotype might be associated with the development of dyslipidemia in ACS patients.

Association between the -794 (CATT)5-8 MIF gene polymorphism and susceptibility to acute coronary syndrome in a western Mexican population.

The macrophage migration inhibitory factor (MIF) is related to the progression of atherosclerosis, which, in turn, is a key factor in the development of acute coronary syndrome (ACS). MIF has a CATT short tandem repeat (STR) at position -794 that might be involved in its expression rate. The aim of this study was to investigate the association between the -794 (CATT)5-8 MIF gene polymorphism and susceptibility to ACS in a western Mexican population. This research included 200 ACS patients classified according to the criteria of the American College of Cardiology (ACC) and 200 healthy subjects (HS). The -794 (CATT)5-8 MIF gene polymorphism was analyzed using a conventional polymerase chain reaction (PCR) technique. The 6 allele was the most frequent in both groups (ACS: 54% and HS: 57%). The most common genotypes in ACS patients and HS were 6/7 and 6/6, respectively, and a significant association was found between the 6/7 genotype and susceptibility to ACS (68% versus 47% in ACS and HS, resp., P = 0.03). We conclude that the 6/7 genotype of the MIF -794 (CATT)5-8 polymorphism is associated with susceptibility to ACS in a western Mexican population.

Assessment of the E-selectin rs5361 (561A>C) polymorphism and soluble protein concentration in acute coronary syndrome: association with circulating levels.

INTRODUCTION: The acute coronary syndrome (ACS) is a complex disease where genetic and environmental factors are involved. E-selectin gene is a candidate for ACS progression due to its contribution in the inflammatory process and endothelial function. The rs5361 (561A>C) polymorphism in the E-selectin gene has been linked to changes in gene expression, affinity for its receptor, and plasmatic levels; therefore it is associated with an increased risk of cardiovascular disease. The aim of this study was to determine the association of the rs5361 polymorphism with ACS and to measure serum levels of soluble E-selectin (sE-selectin). MATERIALS AND METHODS: 283 ACS patients and 205 healthy subjects (HS) from Western Mexico were included. The polymerase chain reaction-restriction fragment length polymorphism was used to determine the rs5361 polymorphism. The sE-selectin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Neither genotype nor allele frequencies of the rs5361 polymorphism showed statistical differences between groups. The sE-selectin levels were significantly higher in ACS patients compared to HS (54.58 versus 40.41 ng/ml, P = 0.02). The C allele had no effect on sE-selectin levels. CONCLUSIONS: The rs5361 E-selectin gene polymorphism is not a susceptibility marker for ACS in Western Mexico population. However, sE-selectin may be a biological marker of ACS.

The 14 bp Del/Ins HLA-G polymorphism is related with high blood pressure in acute coronary syndrome and type 2 diabetes mellitus.

Immunologic and inflammatory processes are involved in the pathogenesis of acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM2). Human leukocyte antigen-G (HLA-G) is a negative regulator of the immune response. This study evaluates the 14 bp Del/Ins HLA-G polymorphism in ACS and DM2. Three hundred and seventy individuals from Western Mexico were recruited and categorized into three groups: ACS (86), DM2 without coronary complications (70), and healthy subjects (214). Genotyping of the 14 bp Del/Ins HLA-G polymorphism was performed by PCR and Native-PAGE. The most common risk factors were hypertension and overweight in ACS and DM2, respectively. The genetic distribution of the 14 bp Del/Ins HLA-G polymorphism showed no significant differences between groups (P ≥ 0.23). Nonetheless, the Ins/Ins genotype was associated with high blood pressure (HBP) in the DM2 group (OR(c) = 1.65, P = 0.02). The genetic recessive model showed similar findings (OR(c) = 3.03, P = 0.04). No association was found in ACS, with a P of 0.05; nevertheless, the prevalence of Ins/Ins carriers was quite similar to that found in the DM2-HBP group. The 14 bp Del/Ins HLA-G polymorphism was not a susceptibility factor for ACS or DM2; however, the Ins/Ins genotype might have contributed to the development of HBP in the studied groups.