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1.
Hum Genomics ; 18(1): 68, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890714

ABSTRACT

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.


Subject(s)
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
2.
Cancer Control ; 30: 10732748231175256, 2023.
Article in English | MEDLINE | ID: mdl-37148308

ABSTRACT

PURPOSE: Identifying actionable oncogenic mutations have changed the therapeutic landscape in different types of tumors. This study investigated the utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) assay, in clinical practice in a developing country. METHODS: In this retrospective cohort study, CGP was performed on clinical samples from patients with different solid tumors recruited between December 2016 and November 2020, using hybrid capture-based genomic profiling, at the individual treating physicians' request in the clinical care for therapy decisions. Kaplan-Meier survival curves were estimated to characterize the time-to-event variables. RESULTS: Patients median age was 61 years (range: 14-87 years), and 64.7% were female. The most common histological diagnosis was lung primary tumors, with 90 patients corresponding to 52.9% of the samples (95% CI 45.4-60.4%). Actionable mutations with FDA-approved medications for specific alterations correspondent to tumoral histology were identified in 58 cases (46.4%), whereas other alterations were detected in 47 different samples (37.6%). The median overall survival was 15.5 months (95% CI 11.7 months-NR). Patients who were subjected to genomic evaluation at diagnosis reached a median overall survival of 18.3 months (95% CI 14.9 months-NR) compared to 14.1 months (95% CI 11.1 months-NR) in patients who obtained genomic evaluation after tumor progression and during standard treatment (P = .7). CONCLUSION: CGP of different types of tumors identifies clinically relevant genomic alterations that have benefited from targeted therapy and improve cancer care in a developing country to guide personalized treatment to beneficial outcomes of cancer patients.


Subject(s)
Developing Countries , Lung Neoplasms , Humans , Female , Middle Aged , Male , Retrospective Studies , Lung Neoplasms/pathology , Mutation , Genomics , High-Throughput Nucleotide Sequencing
3.
JCO Glob Oncol ; 9: e2200377, 2023 05.
Article in English | MEDLINE | ID: mdl-37216624

ABSTRACT

To describe the population with early malignant melanoma, we performed a cohort study on the basis of the Epidemiological Registry of Malignant Melanoma in Colombia-Asociacion Colombiana de Hematologia y Oncologia. From January 2011 until December 2021, 759 patients were included; the average age was 66 years, 57% were women, acral lentiginous histology was found in 27.8% of patients, and the median follow-up was 36.5 months. The prognostic factors for overall survival in our population are Eastern Cooperative Oncology Group 3-4 (hazard ratio [HR], 13.8), stage III (HR, 5.07), received radiotherapy (HR, 3.38), ulceration on histology (HR, 2.68), chronic sun exposure (HR, 2.3), low income (HR, 2.04), previous local surgery (HR, 0.27), and have received adjuvant treatment (HR, 0.41).


Subject(s)
Melanoma , Humans , Female , Aged , Male , Cohort Studies , Prognosis , Colombia/epidemiology , Latin America , Melanoma/diagnosis , Melanoma/epidemiology , Melanoma/therapy , Registries , Melanoma, Cutaneous Malignant
4.
Gac Med Mex ; 159(1): 3-9, 2023.
Article in English | MEDLINE | ID: mdl-36930555

ABSTRACT

INTRODUCTION: The genomic-based 21-gene recurrence score assay (21-GRSA) allows to determine the usefulness of adjuvant chemotherapy in patients with luminal-type early breast cancer (LTEBC). Additional predictive models have also been developed, such as Magee equations (ME), the Predict model (PM), and the Tennessee nomogram score (TNS). OBJECTIVE: To evaluate the concordance between 21-GRSA, ME, PM and TNS. METHODS: Patients with unifocal LTEBC and 21-GRSA, ME, PM and TNS results were included. A subgroup analysis of women older than 50 years was carried out. Concordance between the models and 21-GRSA was evaluated using Cohen's kappa index (KI). RESULTS: One-hundred and twenty-two women were included. Concordance between 21-GRSA and ME (KI = 0.35) and PM (KI = 0.24) was fair (p < 0.001). Concordance between 21-GRSA and TNS was inferior (KI = 0.16, p = 0.04). Eighty patients older than 50 years with sufficient data to calculate all three predictive models were included. Concordance was found between the low-risk classification on 21-GRSA and all three combined models in 36/37 patients (negative predictive value of 97.3%). CONCLUSION: 21-GRSA can be omitted in women older than 50 years with LTEBC classified with low risk scores on all three predictive models.


INTRODUCCIÓN: La prueba genómica de recurrencia de 21 genes (PGR21) permite determinar la utilidad de la quimioterapia adyuvante en pacientes con cáncer de mama temprano luminal (CMTL). Se han desarrollado modelos predictivos adicionales, como las ecuaciones de Magee (EM), el modelo Predict (MP) y la puntuación del nomograma de la Universidad de Tennessee (NT). OBJETIVO: Evaluar la concordancia entre PGR21, EM, MP y NT. MÉTODOS: Se incluyeron pacientes con CMTL unifocal y con resultados de PGR21, EM, MP y NT. Se efectuó subanálisis de mujeres mayores de 50 años. La concordancia se evaluó mediante índice kappa de Cohen (IK). RESULTADOS: Se incluyeron 122 mujeres. La concordancia entre PGR21 y EM (IK = 0.35) y MP (IK = 0.24) fue aceptable (p < 0.001); entre PGR21 y NT fue inferior (IK = 0.16, p = 0.04). Se incluyeron 80 pacientes mayores de 50 años con datos suficientes para calcular los tres modelos. Se encontró concordancia entre la clasificación de bajo riesgo mediante PGR21 y los tres modelos combinados en 36/37 pacientes (valor predictivo negativo de 97.3 %). CONCLUSIÓN: Se puede omitir la PGR21 en las mujeres mayores de 50 años con CMTL que se clasifica de bajo riesgo en los tres modelos predictivos.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Colombia , Risk , Neoplasm Recurrence, Local/genetics , Prognosis
5.
J Investig Med ; 71(5): 502-510, 2023 06.
Article in English | MEDLINE | ID: mdl-36760084

ABSTRACT

Nivolumab is a human programmed death receptor-1 blocking antibody, used as treatment option in patients with advanced non-small-cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second-line (2L) or third-line (3L) therapy in patients with advanced NSCLC. This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as 2L or 3L treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) to treatment. OS and PFS were estimated with the Kaplan-Meier method and the differences were evaluated through the log-rank test. Data of 178 patients were included. The median follow-up was 26.8 months (interquartile range (IQR): 20.3-40.4). Nivolumab was commonly used as a 2L treatment (77.5%). The outcomes in this setting (2L) were as follows: ORR was 21.0%, and the median PFS and OS were 5.5 months (95% confidence interval (CI): 4.5-6.5) and 12.4 months (95% CI: 10.8-14.0), respectively. In 3L, the ORR with nivolumab was 15.0%, the median PFS and OS were 4.1 months (95% CI: 3.1-5.1) and 10.1 months (95% CI: 9.4-10.6), respectively. Three patients (1.7%) required discontinuation due to toxicity. Nivolumab effectiveness and safety in this scenario was consistent with that reported by previous trials and other real-world data.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Nivolumab/therapeutic use , Nivolumab/adverse effects , Lung Neoplasms/drug therapy , Retrospective Studies , Developing Countries , Treatment Outcome
6.
Gac. méd. Méx ; 159(1): 3-9, ene.-feb. 2023. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1448258

ABSTRACT

Resumen Introducción: La prueba genómica de recurrencia de 21 genes (PGR21) permite determinar la utilidad de la quimioterapia adyuvante en pacientes con cáncer de mama temprano luminal (CMTL). Se han desarrollado modelos predictivos adicionales, como las ecuaciones de Magee (EM), el modelo Predict (MP) y la puntuación del nomograma de la Universidad de Tennessee (NT). Objetivo: Evaluar la concordancia entre PGR21, EM, MP y NT. Métodos: Se incluyeron pacientes con CMTL unifocal y con resultados de PGR21, EM, MP y NT. Se efectuó subanálisis de mujeres mayores de 50 años. La concordancia se evaluó mediante índice kappa de Cohen (IK). Resultados: Se incluyeron 122 mujeres. La concordancia entre PGR21 y EM (IK = 0.35) y MP (IK = 0.24) fue aceptable (p < 0.001); entre PGR21 y NT fue inferior (IK = 0.16, p = 0.04). Se incluyeron 80 pacientes mayores de 50 años con datos suficientes para calcular los tres modelos. Se encontró concordancia entre la clasificación de bajo riesgo mediante PGR21 y los tres modelos combinados en 36/37 pacientes (valor predictivo negativo de 97.3 %). Conclusión: Se puede omitir la PGR21 en las mujeres mayores de 50 años con CMTL que se clasifica de bajo riesgo en los tres modelos predictivos.


Abstract Introduction: The genomic-based 21-gene recurrence score assay (21-GRSA) allows to determine the usefulness of adjuvant chemotherapy in patients with luminal-type early breast cancer (LTEBC). Additional predictive models have also been developed, such as Magee equations (ME), the Predict model (PM), and the Tennessee nomogram score (TNS). Objective: To evaluate the concordance between 21-GRSA, ME, PM and TNS. Methods: Patients with unifocal LTEBC and 21-GRSA, ME, PM and TNS results were included. A subgroup analysis of women older than 50 years was carried out. Concordance between the models and 21-GRSA was evaluated using Cohen's kappa index (KI). Results: One-hundred and twenty-two women were included. Concordance between 21-GRSA and ME (KI = 0.35) and PM (KI = 0.24) was fair (p < 0.001). Concordance between 21-GRSA and TNS was inferior (KI = 0.16, p = 0.04). Eighty patients older than 50 years with sufficient data to calculate all three predictive models were included. Concordance was found between the low-risk classification on 21-GRSA and all three combined models in 36/37 patients (negative predictive value of 97.3%). Conclusion: 21-GRSA can be omitted in women older than 50 years with LTEBC classified with low risk scores on all three predictive models.

7.
Lancet Oncol ; 23(7): e348-e358, 2022 07.
Article in English | MEDLINE | ID: mdl-35772466

ABSTRACT

In a multiday conference, a panel of Latin American experts in biological cancer therapies and health economics were provided with questions to address the barriers restricting access to biosimilars in Latin America, specifically for patients with breast cancer and colorectal cancer, for whom biosimilars can be a path forward to increasing access to care. During the conference, responses were discussed and edited until a consensus was achieved. The regulatory challenges identified in the conference included heterogenous regulations, non-adherence to regulatory pathways, scarcity of market opportunity, inadequate naming of biosimilars by only using international non-proprietary names, imprecise use of interchangeability and substitution, and insufficient traceability and pharmacovigilance. Recommendations were developed to improve the implementation of regulatory pathways and reliable procurement strategies that increase access to these therapies with adequate traceability and outcome measures; efforts from all involved stakeholders will be crucial. These recommendations can serve as a strategy for biosimilar adoption in other countries in a similar situation.


Subject(s)
Biosimilar Pharmaceuticals , Breast Neoplasms , Colorectal Neoplasms , Biosimilar Pharmaceuticals/adverse effects , Breast Neoplasms/drug therapy , Colorectal Neoplasms/drug therapy , Female , Humans , Latin America/epidemiology , Pharmacovigilance
8.
Biomedicines ; 10(3)2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35327380

ABSTRACT

BACKGROUND: Novel combination therapies have been shown to improve the outcomes of treatment-naive patients with locally advanced or metastatic renal cell carcinoma (aRCC). However, the optimal systemic therapy for aRCC of favorable risk has yet to be clarified. We aimed to evaluate the efficacy and safety of different immunotherapy (IO) combinations, either with another IO (IO-IO) or with an antiangiogenic (IO-TKI), versus sunitinib in the first-line setting in aRCC patients with favorable IMDC risk. METHODS: We conducted a systematic search for evidence in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials published up to February 2021. The GRADE approach was used to assess the quality of evidence. Survival hazard ratios were extracted for analysis in the favorable-risk aRCC subgroup (IMDC). A sensitivity analysis was performed excluding trials of combination therapy without TKI. RESULTS: Five randomized controlled phase III trials with a total of 1088 patients were included in the analysis. The studies compared different combinations versus sunitinib monotherapy. All clinical trials reported overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) data. Four out of five trials reported complete response (CR). There was no difference in OS nor PFS between treatment arms in the IMDC favorable-risk subgroup analysis (OS: HR = 1.07, 95% CI = 0.81-1.41; PFS: HR = 0.74, 95% CI = 0.46-1.19). A benefit in ORR and CR was found for combination therapy vs. sunitinib (ORR: HR = 1.89, 95% CI = 1.29-2.76; CR: HR = 3.58, 95% CI = 2.04-6.28). In the sensitivity analysis, including only IO-TKI vs. sunitinib, no difference in OS was found; however, an advantage in PFS was observed (OS: HR = 0.99, 95% CI 0.69-1.43; PFS: HR = 0.60 (0.45-0.81). The safety profile reported is consistent with previous reports. We did not find differences in the incidence of any adverse event (AE) or of grade ≥3 AEs. CONCLUSION: This meta-analysis shows that combinations of IO-KI as first-line treatment in favorable-IMDC-risk aRCC improve PFS, ORR, and CR, but not OS, versus sunitinib.

9.
JCO Glob Oncol ; 7: 1012-1023, 2021 06.
Article in English | MEDLINE | ID: mdl-34185572

ABSTRACT

Given the benefits and likely future applications, there is an urgent need to expand the use of next-generation sequencing (NGS) in breast, lung, and unknown primary cancers in Colombia. The objective of this review is to address the barriers limiting access to the use of NGS in Colombia, specifically for patients with breast, lung, and unknown primary cancers in the public health care system. A selected Panel of Colombian experts in NGS were provided with a series of relevant questions to address in a multiday conference. Each narrative was discussed and edited by the Panel through numerous drafts and rounds of discussion until consensus was achieved. There are limitations to the widespread adoption of innovative technology inherent to the Colombian health care system. Barriers identified to implementing NGS in Colombia include availability, accessibility, and affordability; limited infrastructure; training and awareness of health personnel; quality-control procedures; and collection of local data. Stakeholders must align to adapt the implementation of NGS to the constraints of resource-limited environments. Diagnostic algorithms were developed to guide molecular testing for lung, breast, and unknown primary cancers. Recommendations on overcoming the barriers to the widespread adoption of NGS include country-specific molecular testing guidelines, creating a national genetic registry, improving infrastructure, and creating health policy that favors the adoption of innovative technology.


Subject(s)
Neoplasms, Unknown Primary , Colombia , Consensus , High-Throughput Nucleotide Sequencing , Humans , Lung
10.
Oncologist ; 24(8): e709-e719, 2019 08.
Article in English | MEDLINE | ID: mdl-30910864

ABSTRACT

The participation of patients in precision oncology trials needs to fulfill molecular-based selection criteria. This strongly limits accrual, and as a consequence, screening successes have decreased, costs have increased, and fewer subjects are enrolled. To achieve narrowed targets, studies have been forced to be multicenter and multinational to reach a larger pool of candidates. However, this globalization faces many challenges, as, for example, in the case of precision oncology trials. These trials have a complex structure that is dependent upon a high-tech infrastructure and knowledge in a dynamic environment. Given the movement of precision clinical cancer research to regions other than Europe and the U.S., it is important to evaluate the feasibility of performing such trials in lower-middle- and low-income countries. Here we critically discuss the advantages of conducting precision oncology clinical trials in Latin America and make suggestions on how to overcome the main challenges involved. IMPLICATIONS FOR PRACTICE: Precision clinical trials in oncology are studies that require candidates to have tumors with specific molecular alterations, which are considered the target for the trial experimental therapy. Because many molecular alterations are rare, fewer patients are enrolled. This has led to trials being forced to be multicenter and multinational, including trials in Latin America. This article discusses the challenges and opportunities to conduct precision oncology trials in Latin America, aiming to help sponsors and investigators to solve complex issues that ultimately lead to more of such trials being run in the region, potentially benefiting more Latin American patients with cancer.


Subject(s)
Clinical Trials as Topic/methods , Molecular Targeted Therapy/methods , Neoplasms/drug therapy , Precision Medicine/methods , Clinical Trials as Topic/standards , Humans , Internationality , Latin America , Molecular Targeted Therapy/standards , Multicenter Studies as Topic , Neoplasms/pathology , Precision Medicine/standards
11.
Lung Cancer ; 125: 265-272, 2018 11.
Article in English | MEDLINE | ID: mdl-30429031

ABSTRACT

OBJECTIVES: Contrasting other EGFR mutations (EGFRm) in lung adenocarcinomas, insertions in exon 20 (exon20ins) are generally associated with resistance to targeted therapy, limiting therapeutic options and impoverishing the prognosis compared to other EGFRm. We sought to extensively characterize exon20ins from a large cohort of lung adenocarcinomas in Hispanic patients. MATERIALS AND METHODS: This was a region-wide, observational longitudinal cohort study to evaluate characteristics and outcomes of patients with exon20ins in lung adenocarcinoma, based on a secondary analysis of electronic records from the Geno1.2-CLICaP Platform and extended genotype testing. Patients from six Latin-American countries were included (Argentina, Colombia, Costa Rica, Ecuador, Panama, and Mexico). Data obtained included the molecular spectrum (extended genotyping for mutations in BRAF, NRAS, PIK3CA, Her2 and MEK1, as well as for EGFR amplification, ALK and PD-L1 protein expression), clinic-pathologic characteristics, prevalence and outcomes to therapeutic approach. RESULTS AND CONCLUSIONS: 4.005 patients diagnosed with stage III/IV lung adenocarcinoma from 2011 to 2016 were initially screened. Among these, 88 patients had a confirmed exon20 in. and were included; median age was 66-years, 62.5% were females, 64% were never smokers and 39% presented with brain metastases. The H773insH variant was the most frequent, making up 21.6% of cases. A common EGFRm was concomitantly found in 36.4% (del19/L858R), and 8% (G719X/L861Q/S768I) of cases. Five cases had additional mutations in PI3K, KRAS and MEK1, 26% had EGFR amplification and 81.7% had PD-L1 expression 1-50%. Overall response rate to first-line therapy was 28% and overall survival was 16.4 months. Prognosis was positively influenced by the concomitant presence of common EGFRm and response to first-line. Our results suggest that patients with EGFR exon20ins have similar clinical characteristics to those with common EGFRm but a poorer prognosis. Last, the mean PD-L1 expression in this population seems higher than for patients with common EGFRm.


Subject(s)
Adenocarcinoma of Lung/genetics , Exons/genetics , Hispanic or Latino/genetics , Lung Neoplasms/genetics , Mutation/genetics , Aged , ErbB Receptors/genetics , Female , Humans , Longitudinal Studies , Male
12.
Oncology ; 94(5): 297-305, 2018.
Article in English | MEDLINE | ID: mdl-29510386

ABSTRACT

OBJECTIVE: This study describes the real-world characteristics, treatment sequencing, and outcomes among Hispanic patients with locally advanced/metastatic ALK-positive non-small-cell lung cancer (NSCLC) treated with crizotinib. METHODS: A retrospective patient review was conducted for several centers in Latin America. Clinicians identified ALK-positive NSCLC patients who received crizotinib and reported their clinical characteristics, treatments, and survival. Overall survival and progression-free survival (PFS) were described. A Random Forest Tree (RFT) model was constructed to predict brain progression. RESULTS: A total of 73 patients were included; median age at diagnosis was 58 years, 60.3% were female, and 93.2% had adenocarcinoma. Eighty-nine percent of patients were never smokers/former smokers, 71.1% had ≥2 sites of metastasis, and 20.5% had brain metastases at diagnosis. The median PFS on first-line crizotinib was 7.07 months (95% CI 3.77-12.37) and the overall response rate was 52%. Of those who discontinued crizotinib, 55.9% progressed in the central nervous system (CNS). The RFT model reached a sensitivity of 100% and a specificity of 88% for prediction of CNS progression. CONCLUSIONS: The overall response rate and the PFS observed in Hispanic patients with ALK-positive NSCLC treated with first-line crizotinib were similar to those in previous reports. An RFT model is helpful in predicting CNS progression and can help clinicians tailor treatments in a resource-limited practice.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Disease Progression , Disease-Free Survival , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Receptor Protein-Tyrosine Kinases/metabolism , Adult , Aged , Aged, 80 and over , Anaplastic Lymphoma Kinase , Carcinoma, Non-Small-Cell Lung/physiopathology , Crizotinib , Female , Follow-Up Studies , Humans , Latin America , Lung Neoplasms/physiopathology , Male , Middle Aged , Retrospective Studies
13.
Hered Cancer Clin Pract ; 12(1): 11, 2014.
Article in English | MEDLINE | ID: mdl-24742220

ABSTRACT

BACKGROUND: Approximately 5% of all breast cancers can be attributed to a mutation in the BRCA1 or BRCA2 gene. The genetic component of breast cancer in Colombia has been, for the most part, studied on cases from the Bogota region. Five different founder mutations were in two studies of breast cancer patients in the Bogota region. It is important that the frequency of mutations be established among unselected cases of breast cancer of other regions of Colombia in order to estimate the genetic burden of this cancer in Colombia and to plan genetic services. The aim of this study was to establish the mutation frequencies of the BRCA genes in breast cancer patients unselected for family history or age, from Medellin, Colombia. METHODS: We enrolled 280 unselected women with breast cancer from a large public hospital in Medellin, Colombia. A detailed family history from each patient and a blood sample was obtained and processed for DNA analysis. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques including a panel of recurrent Hispanic BRCA mutations which consists of fifty BRCA1 mutations and forty-six BRCA2 mutations, including the five recurrent Colombian BRCA mutations. All mutations were confirmed by direct sequencing. RESULTS: Genetic testing was successfully completed for 244 of the 280 cases (87%). Among the 244 cases, three deleterious mutations were identified (two in BRCA1 and one in BRCA2) representing 1.2% of the total. The average age of breast cancer in the mutation-positive cases was 34 years. The two BRCA1 mutations were known founder mutations (3450del4 in exon 11 and A1708E in exon 18). The BRCA2 mutation was in exon 11 (5844del5) and has not been previously reported in individuals of Colombian descent. Among the three mutation-positive families was a breast cancer family and two families with no history of breast or ovarian cancer. CONCLUSION: The frequency of BRCA mutations in unselected breast cancer cases from the Medellin region of Colombia is low and is approximately 1.2%.

14.
Rev. venez. oncol ; 25(2): 117-125, abr.-jun. 2013.
Article in Spanish | LILACS | ID: lil-718942

ABSTRACT

La ixabepilona es un análogo semisintético de la epotilona B se une directamente a las subunidades de β-tubulina en los micro túbulos, lo que conduce a la muerte celular. Aunque los resultados de ensayos clínicos de ixabepilona han sido alentadores, la edad media de los pacientes en estos estudios fue de alrededor de 52 años. El cáncer de mama en mujeres más jóvenes (<40 años) tiene una fisiopatología más agresiva, con mayor riesgo de recurrencia y resultados inferiores. Hay poca información disponible sobre el tratamiento del cáncer de mama en América Latina, que puede ser especialmente difícil debido a consideraciones financieras y problemas con el acceso a los servicios de salud. Esta serie de estudios de casos y revisión proporciona información sobre el uso de ixabepilona para el tratamiento de mujeres jóvenes con cáncer de mama en América Central y del Sur.


The ixabepilona is a semi-synthetic analog of the epotilona B it has a directly union of sub unity of β-tubuline in the micro tubules, it mechanism conduce to the cellular death. The results of the clinical studies of ixabepilona were encouraging; the middle age of the patients in these studies was of 52 years old. The breast cancer in young women less than (<40 years) has a physiopathology more aggressive with mayor risk of recurrence and we obtain inferior results. There is little available information about the breast cancer in Latin America; it has been especially difficult for the financial considerations and problems with the access to the health services. In these series of clinical cases and revision let us information about the use of ixabepilona for the treatment of young women with breast cancer in Central America and in the Sur.


Subject(s)
Humans , Female , Adult , Neoplasm Metastasis/diagnosis , Neoplasm Metastasis/drug therapy , Neoplasm Metastasis/therapy , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Breast Neoplasms/rehabilitation , Breast Neoplasms/therapy , Latin America , Pharmacology , Medical Oncology , Therapeutics
15.
CES med ; 25(2): 213-220, jul.-dic. 2011. ilus, tab
Article in Spanish | LILACS | ID: lil-616578

ABSTRACT

Presentamos dos casos de pacientes con leucemia linfoblástica en tratamiento con quimioterapia (HyperCVAD), el primero y el segundo en recaída con IdaFlag, quienes en fase de neutropenia desarrollan cuadro de neumonía adquirida hospitalariamente con consolidación neumónica fiebre alta y pocos síntomas respiratorios El antígeno urinario para Legionella pneumophila serotipo 1 resultó positivo por técnica de inmunocromatog rafía. Con tratamiento específico con claritromicina resolvieron sus síntomas.


We present two cases of patients with lymphoblastic leukemia; the first one is been treated with chemotherapy (hyperCVAD) and the second is in a relapse with IdaFlag, both, in neutropenia phase developed pneumonia acquired in the hospital with pneumonic consolidation, high fever and few respiratory symptoms. Legionella urinary antigen serogroup 1 was positive for the immunechromatography technique. Specific treatment with macrolides was given and the symptoms were solved.


Subject(s)
Humans , Bacteria , Legionella , Leukemia , Neutropenia , Pneumonia
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