ResumenLas mutaciones de BRCA1 son raras en el cáncer de mama (CM) esporádico; sin embargo, su expresión a nivel tumoral se encuentra disminuida o ausente en 30%-50% de los casos.Objetivo: valorar la expresión tumoral de BRCA1 por inmunohistoquímica (IHQ) en mujeres uruguayas diagnosticadas de CM antes de los 40 años.Material y método: se incluyeron pacientes diagnosticadas de CM antes de los 40 años. Se utilizaron los anticuerpos monoclonales anti-BRCA1 MS110 contra el extremo N-terminal y GLK-2 contra el extremo C-terminal. Se calculó la sobrevida global (SVG) y la sobrevida libre de enfermedad (SVLE), para la construcción de las curvas se utilizó el método de Kaplan-Meier y la diferencia de sobrevida se evaluó mediante el test de log rank.Resultados: se incluyeron 40 pacientes, la SVG y la SVLE a cinco años fueron de 73% y 60% respectivamente. La expresión de BRCA1 mediante GLK-2 fue £10% en 16 de las 40 pacientes (40%). La SVG y la SVLE a cinco años para las pacientes con expresión £10% fue de 56% vs 85% para las pacientes con expresión >10% (p=0,015) y de 40% vs 72% (p=0,034) respectivamente. La expresión de BRCA1 mediante MS110 fue £10% en 11 de las 40 pacientes (27,5%). No se encontraron diferencias en la SVG ni en la SVLE a cinco años con este marcador.Conclusión: la pérdida de la expresión tumoral de BRCA1 determinada mediante GLK-2 se encontró en el 40% de las pacientes incluidas y se asoció a una menor SVG y SVLE, por lo que podría tener un valor pronóstico desfavorable en estas pacientes.

e12028 Background: BRCA1 is one of the main susceptibility genes for breast cancer (BC). While BRCA1 mutations are rare in sporadic tumors, loss or reduction of gene expression have been reported in approximately 30-50% of sporadic BCs in the general population. From the molecular point of view, there is no clear characterization of these tumors in young women and we have found no studies reporting the rate of under-expression of BRCA1 in women with sporadic BC under 40 years of age. Objective: to assess the tumor expression of BRCA1 using immunohistochemistry (IHC) and its prognostic value in Uruguayan women diagnosed with BC before the age of 40 years. Methods: IHQ was used to analyze the tumor expression of BRCA1 in paraffin-embedded tumor samples of 40 BC patients diagnosed before the age of 40 between 01/01/2006 and 12/31/2012. The optimization and determination of the BRCA1 protein by IHC was centralized. The antibodies used were anti BRCA1 MS110 monoclonal antibodies against the N-terminal end and GLK-2 against the C-terminal end (amino acids 1839-1863). Expression was considered positive when >10% of the cells had nuclear and/or cytoplasmic labeling. Overall survival (OS) and disease free survival (DFS) were calculated; the curves were developed using the Kaplan-Meier method and the difference in survival was evaluated through the log rank test. Results: the average age of the 40 patients included was 36 years; 8 patients (20%) had significant family history of BC or ovarian cancer. The distribution by stage (S) was as follows: SI: 9 patients (22.5%); SII: 20 patients (50%); SIII: 10 patients (25%), and SIV: 1 patient. Regarding the biological profile: 17 patients (42.5%) were HER2- and ER/PR+, 13 (32.5%) were HER2+ and the remaining 10 patients (25%) were classified as triple negative. The 5-year OS and DFS were 73% and 60% respectively. The expression of BRCA1 with GLK-2 was ≤10% in 16 of the 40 patients included (40%). The 5-year OS and DFS for patients with ≤10% expression was 56% vs. 85% for patients with >10% (p = 0.015) and 40% vs. 72% (p = 0.034) respectively. The expression of BRCA1 by MS110 was ≤10% in 11 of the 40 patients included (27.5%). No statistically significant differences were found in the 5-year OS or DFS based on the expression of this marker. Conclusions: Decreased BRCA1 tumor expression as assessed by IHC using GLK-2 was found in 40% of young patients included and was associated with unfavorable prognosis.

No abstract