BACKGROUND: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted. RESULTS: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure. CONCLUSION: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.
BRCA2 Protein , Breast Neoplasms , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Female , Germ-Line Mutation/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Breast Neoplasms/epidemiology , Colombia/epidemiology , Middle Aged , Adult , BRCA2 Protein/genetics , BRCA1 Protein/genetics , Exome Sequencing , Aged , Genetic Testing/methods , Ataxia Telangiectasia Mutated Proteins/genetics
Introducción. La neuropatía periférica inducida por quimioterapia es una reacción común a una variedad de medicamentos usados en el tratamiento del cáncer, que consiste principalmente en síntomas sensitivos, con componentes motores y cambios autonómicos. La prevalencia es del 30-68% después de terminar la quimioterapia en países no latinoamericanos. Objetivo. Determinar la prevalencia de la neuropatía periférica inducida por quimioterapia en la población colombiana. Pacientes y métodos. Estudio retrospectivo con evidencia del mundo real en la totalidad de pacientes atendidos en cuatro centros oncológicos de Colombia, quienes recibieron terapia farmacológica para algún tipo de cáncer entre enero de 2015 y diciembre de 2016 con taxanos (paclitaxel, docetaxel), agentes alquilantes (oxaliplatino), inhibidores de proteasoma (bortezomib) y análogos de epotilona B (ixabepilona). Resultados. Se siguió a un total de 1.551 pacientes en cuatro ciudades a quienes se les aplicaron 11.280 dosis, con predominio femenino (n = 1.094; 70,5%) y una edad media de 57 ± 13 años. El paclitaxel fue el fármaco más prescrito (n = 788; 50,8%). La neuropatía inducida por quimioterapia se presentó en el 48,9% de los pacientes con paclitaxel, el 58,5% de los pacientes con oxaliplatino, el 50,5% de los pacientes con docetaxel, el 43,7% de los pacientes con bortezomib y el 95,2% de los pacientes con ixabepilona. Se trató a 33 pacientes con dos de estos medicamentos simultáneamente. Conclusiones. La neuropatía periférica inducida por quimioterapia es una reacción adversa frecuente en pacientes con cáncer en Colombia tratados con taxanos, alquilantes, inhibidores de proteasoma e ixabepilona. Es necesario establecer métodos diagnósticos efectivos e incorporar escalas validadas en la evaluación rutinaria de los pacientes que reciben estas medicaciones
Introduction. Chemotherapy-induced peripheral neuropathy is a common adverse reaction in a variety of medications frequently used for a great number of cancer treatments. This condition consists of mainly sensory-type symptoms, motor components and autonomic changes. Reported prevalence ranges from 30-68%, after the completion of chemotherapy in non-Latin American people with different populations and socioeconomic levels. Aim. To determine the prevalence of chemotherapy-induced peripheral neuropathy in a Colombian population. Patients and methods. A real-world evidence cross-sectional retrospective study was performed in all patients from oncological clinical centers in Colombia, which received pharmacological therapy for any cancer between January 2015 and December 2016, with taxanes (paclitaxel, docetaxel), alkylators (oxaliplatin), proteasome inhibitors (bortezomib), and epothilone B analogs (ixabepilone). Results. A total of 1,551 patients in four cities were included, and 11,280 doses were applied; predominantly females (n = 1,094; 70.5%), with a mean age of 57 ± 13 years old. Paclitaxel was the most commonly prescribed drug (n = 788; 50.8%). Chemotherapy-induced peripheral neuropathy was developed in 48.9% of paclitaxel, 58.5% of oxaliplatin, 50.5% of docetaxel, 43.7% of bortezomib and 95.2% of ixabepilone patients. Thirty-three patients were treated with two of these medications simultaneously. Conclusions. Chemotherapy-induced peripheral neuropathy is a frequent adverse reaction to daily cancer therapy in Colombian patients managed with taxanes, alkylators, proteasome inhibitors, and epothilone B analogs. Hence, it is necessary to establish more successful diagnostic methods and incorporate validated scales in the routine evaluation of all patients receiving these medications in our environment
Humans , Male , Female , Adult , Middle Aged , Aged , Antineoplastic Agents/adverse effects , Peripheral Nervous System Diseases/chemically induced , Prevalence , Antineoplastic Agents/therapeutic use , Colombia , Retrospective Studies , Cross-Sectional Studies , Socioeconomic Factors , Neoplasms/drug therapy
Introducción: Se describe una serie casos de cáncer en el periodo 2001-2011 de usuarios atendidos en Oncólogos del Occidente que permite establecer una tendencia de la notificación de los casos a través del tiempo. Métodos: Se diseñó un sistema de información de cáncer en Oncólogos del Occidente tomando como fuente la historia clínica digital de la institución. Resultados: En el periodo de observación, los cánceres que más generan consulta en las diferentes sedes de Oncólogos del Occidente están localizados en próstata, mama, cérvix, gástrico, bronquios y pulmón, linfomas, colon, recto, tiroides, ovario y leucemias linfoides. Discusión: Casi todos los cánceres aquí definidos como importantes por su frecuencia pueden ser intervenidos de una manera precoz, con adecuados programas de promoción de la salud y tamizajes que son costo-efectivos.
Introduction: The document establishes the tendencies of cancer cases through time. It describes the series of cancer cases for patients who attended the Oncologos del Occidente during the period of 2001-2011. Methods: To accomplish this, Oncologos del Occidente designed an information system that used as a main source the digital clinical history of the institution. Results: During the period of observation, the most prevalent cancers requiring medical consultation throughout the centers of Oncologos del Occidente were: prostate, breast, cervical, stomach, bronchial tubes and lung, lymphoma, colon, rectum, thyroid, ovarian, and lymphoid leukemia. Discussion: Most of the cancers defined as important by their frequency in this document, can be early intervened through appropriate cost-effective health and screening promotional programs.
Humans , Epidemiology , Neoplasms , Surveillance in Disasters , Colombia
