Prevalence of BRCA1 and BRCA2 germline mutations in patients of african descent with early-onset and familial Colombian breast cancer

Q2Q1Familias afrocolombianas afectadas por cáncer de mama y ovarioBackground: Pathogenic germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes contribute to hereditary breast/ovarian cancer (OC) in White/mestizo Colombian women. As there is virtually no genetic data on breast cancer (BC) in Colombians of African descent, we conducted a comprehensive BRCA1/2 mutational analysis of 60 Afro-Colombian families affected by breast/OC. Materials and Methods: Mutation screening of the complete BRCA1/2 genes for small-scale mutations and large genomic alterations was performed in these families using next-generation sequencing and multiplex ligation-dependent probe amplification analysis. Results: Four pathogenic germline mutations, including one novel mutation, were identified, comprising 3 in BRCA1 and one in BRCA2. The prevalence of BRCA1/2 mutations, including one BRCA1 founder mutation (c.5123C>A) previously identified in this sample set, was 3.9% (2/51) in female BC-affected families and 33.3% (3/9) in those affected by both breast and OC. Haplotype analysis of 2 BRCA2_c.2701delC carriers (one Afro-Colombian and one previously identified White/mestizo Colombian patient with BC) suggested that the mutation arose in a common ancestor. Conclusion: Our data showed that 2/5 (40%) mutations (including the one previously identified in this sample set) are shared by White/mestizo Colombian and Afro-Colombian populations. This suggests that these 2 populations are closely related. Nevertheless, variations in the BRCA1/2 mutational spectrum among Afro-Colombian subgroups from different regions of the country were observed, suggesting that specific genetic risk assessment strategies need to be developed.https://orcid.org/0000-0002-1903-9621https://orcid.org/0000-0001-6444-7248https://orcid.org/0000-0002-3649-9515https://orcid.org/0000-0002-9879-9775Revista Internacional - IndexadaA1N

Low Prevalence of the Four Common Colombian Founder Mutations in BRCA1 and BRCA2 in Early-Onset and Familial Afro-Colombian Patients with Breast Cancer

Q1Q1Artículo académicoe475-e479.Background. Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. In Colombian Hispanic families, four common BRCA1/2 founder mutations have previously been identified. Because nothing is known about the contribution of BRCA1/2 germline mutations to early-onset and hereditary breast and/or ovarian cancer in Afro-Colombians, we conducted the first study on 60 patients with early-onset and familial breast cancer in this population. Materials and Methods. Screening for the four Colombian founder mutations BRCA1/c.3331_3334delCAAG, BRCA1/ c.5123C>A, BRCA2/c.2806_2809delAAAC, and BRCA2/ c.1763_1766delATAA was performed using mismatch polymerase chain reaction (PCR) analysis, PCR-based restriction fragment length polymorphism analysis, and qualitative real-time PCR. Mutations were confirmed by direct DNA sequencing. Results. The BRCA1 founder mutation c.5123C>A was identified in one family with breast and ovarian cancer (1/60, 1.7%). Three women were diagnosed with breast cancer, including one with bilateral disease, at the ages of 30, 30/33, and 52 years, and one woman was diagnosed with ovarian cancer at the age of 60 years. Conclusion. Our data showed a low prevalence of the BRCA1/2 founder mutations in Colombians of African descent, implying that these mutations should not be recommended for genetic screening programs in the Afro-Colombian population

Mastitis granulomatosa crónica lobular idiopática: una patología vigente Chronic idiopathic lobular granulomatous mastitis: a current pathology

Introducción: La mastitis granulomatosa crónica lobular idiopática es una patología benigna del seno, de carácter inflamatorio y de etiología desconocida. Sus principales manifestaciones clínicas se semejan a las del cáncer mamario. Dado que los hallazgos clínicos y de imágenes diagnósticas no son específicas, el diagnóstico inequívoco recae en el estudio histopatológico de 0 lesión. Objetivos: Describir las principales manifestaciones clínicas, los resultados de los métodos diagnósticos y hallazgos importantes de patología en los casos de mastitis granulomatosa crónica lobular idiopática. Materiales y métodos: Desde enero del año 2004 los autores establecieron el registro personal de tumores benignos, mastitis no lactacional y enfermedad inflamatoria ductal. Hasta septiembre de 2006, este registro recolectó información clínica, métodos diagnósticos y tratamiento en 77 pacientes, 20 de los cuales correspondieron al diagnóstico de mastitis granulomatosa crónica lobular idiopática. Se realizó análisis estadístico descriptivo por las siguientes variables: 1. Edad. 2. Cuadro clínico. 3. Enfermedades asociadas. 4. Métodos diagnósticos utilizados. 5. Hallazgos histopatológicos. 6. Curso clínico. Resultados: El diagnóstico de mastitis granulomatosa crónica lobular se hizo inicialmente en 30 pacientes. Se confirmó el diagnóstico de mastitis granulomatosa crónica lobular idiopática en 20 pacientes, dado que en 10, se identificó la causa específica de la inflamación granulomatosa del seno. La edad promedio de las pacientes fue de 36 años; la más joven tenía 22 años. La manifestación clínica más frecuente fue la aparición de masa inflamatoria en el seno. El hallazgo principal del estudio fue la asociación de mastitis granulomatosa crónica lobular idiopática con cáncer del seno contralateral y la infección con virus de inmunodeficiencia humana, asociación no descrita en la literatura mundial. Conclusión: El diagnóstico de mastitis granu-lomatosa crónica lobular idiopática es un reto clínico formidable. Debido a que sus manifestaciones clínicas son yerras y se observa resolución espontánea de la enfermedad, esta patología posiblemente es dejada sin diagnosticar en una proporción importante de casos. La identificación de la causa subyacente de la inflamación granulomatosa en más de un tercio de los pacientes, hace que el estudio histopatológico sea considerado por nosotros como el método diagnóstico de escogencia para el diagnóstico incuestionable de esta patología.Background: Chronic idiopathic granulomatous mastitis (ICGM) is a benign disease of the breast, of inflammatory nature and unknown etiology. The main clinical features of this entity resemble those of mammary cancer. Given that the clinical and diagnostic imaging findings are not specific, the correct diagnosis falls in the histopathologic study. Objectives: To describe the main clinical manifestations, the results of the diagnostic studies, and the most important findings in the pathlogical study of ICGM. Materials and methods: Beginning in January 2004, the authors implemented the personal registry of benign breast tumors, nonlactational mastitis, and ductal inflammatory disease; 77 patients were registered until September 2006, with data including clinical information, diagnostic methods, and treatment modalities. In this group of 77 patients, 20 had the diagnosis of ICGM. A descriptive statistical analysis based on the following variables was carried out: 1. Age; 2. Clinical presentation; 3. Associated illnesses; 4. Diagnostic methods employed; 5. histopathologic findings; 6. Clinical course. Results: The diagnosis of ICGM was initially made in 30 patient, and the diagnosis was confirmed in 20, while in the other 10 a specific inflammatory cause was identified. The average age of this group patients was 36 years, the youngest being 22.The most frequent clinical presentation was an inflammatory mass in the breast, while the outstanding finding was the association of ICGM with contralateral breast cancer and infection with HIV, an association that has not been reported in the literature. Conclusion: The diagnosis of ICGN represents a formidable clinical challenge, by virtue of the ambiguous clinical manifestations and the fact that the entity tends to resolve spontaneously. Thus, it is possible that ICGM remains undiagnosed in a significant number of cases. The identification of the underlying cause of ICGM in more than one third of our patients indicates that the histopathologic study is the should be considered as the only certain diagnostic method