RESUMO
El cáncer de mama es uno de los principales problemas de salud y, aproximadamente, 10% de los casos son de origen genético. En un estudio previo realizado por nosotros, se encontraron mutaciones fundadoras en los genes BRCA1 y BRCA2; esto permite trazar estrategias de detección temprana para personas con alta susceptibilidad en Colombia e implementar medidas profilácticas. El objetivo de este estudio fue estimar el componente genético del cáncer de mama en Colombia, mediante el estudio de la frecuencia y penetrancia de las mutaciones germinales en BRCA1 y BRCA2. Se estudiaron 766 pacientes que cumplieron el criterio de habérseles diagnosticado cáncer de mama después de 2004 y se realizaron estudios moleculares para las mutaciones fundadoras. Se entregaron los resultados a las pacientes y se analizaron los datos para frecuencia y penetrancia. La frecuencia total para mutaciones fundadoras para BRCA1 y BRCA2 fue de 4,2% (IC95% 2,9-5,8), y la penetrancia a los 50 años fue de 33,3 (IC95% 15,2-63,1) para BRCA1 y de 32 (IC95%11,8-70,9) para BRCA2 La alta frecuencia de mutaciones justifica la necesidad de ofrecer este tipo de examen a mujeres con cáncer de mama, independientemente de los antecedentes.Es necesario ampliar los estudios para realizar cálculos de penetrancia a los 70 años...
Breast cancer is one of the main public health problems, approximately 10% are genetic. In a previous study carried out by our group, founder mutations in BRCA1 and BRCA2 genes were detected; this will allow early testing and detection of patients with high breast and ovarian cancer susceptibility in Colombia, and to implement prophylactic strategies. The aim of this study was to estimate the genetic component of breast cancer in Colombia, testing for the frequency and penetrance of germinal mutations in BRCA1 and BRCA2. 766 patients fulfilling the criteria of breast cancer diagnosis after 2004 were studied for founder mutations. The results were reported to the patients; frequency and penetrance were tested. Total frequency for founder mutations in BRCA1 and BRCA2 was 4.2% (CI 95%: 2.9-5.8), and penetrance at 50 years was 33, 3(CI 95%: 15.2 - 63.1) for BRCA1 and 32(CI 95%:11.8 - 70.9) for BRCA2. The high frequency of the mutations supports the need to implement genetic testing policy for patients with breast cancer independently of family history or age. It is necessary to continue the study to perform penetrance testing at the 70 year limit...
Assuntos
Mutação , Neoplasias da MamaRESUMO
PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer. EXPERIMENTAL DESIGN: We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated. RESULTS: Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P < 0.0001), had a higher percentage solid component (P = 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers. CONCLUSIONS: Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively aggressive and may be expected to have poor prognosis, although this may be treatment dependent.
