Impact of BRCA mutation status on the clinical phenotype and survival of hereditary breast cancer.

22037 Background: In a multidisciplinary program supported by the German Cancer Aid in 1996-2006 a total of 3.408 women with a family history for breast and/or ovarian cancer were genetically counselled and tested for BRCA-1 and BRCA-2 mutations.,The mutations were detected using DHPLC and direct sequencing. The family history of breast and/or ovarian cancer was proven by collecting medical reports of family members. The statistical analysis was done using standard procedures (Kaplan-Meier-analysis, t-test, chi-square-test).,Among the women with breast cancer 566 showed a deleterious BRCA1 and 313 a BRCA2 mutation. Four women were found to have mutations in both genes and 2.525 were BRCA-1/2 negative. In accordance with the literature we found the phenotype "hormone receptor negative and grade 3" as well as the medullary subtype significantly more often in BRCA1 associated breast cancers (74% vs. 24%, 63% vs. 42% and 10% vs. 5%). The median age of onset was significantly lower in BRCA1 mutation carriers (38 yrs) compared to BRCA2 mutation carriers (45 yrs) and women tested negative for BRCA1 and BRCA2 mutations (46 yrs) as well as sporadic breast cancer cases within these families (52 yrs). The median age of the 4 women with mutations in both genes was even lower (median age 33.5 yrs). Although BRCA2 associated breast carcinomas presented in more advanced stages (N+ in 44% [118/257] compared to BRCA-1 positive in 31% [166/519], p<0.01) there was no difference in overall survival between BRCA1 and BRCA2 mutation carriers. However, BRCA1 and BRCA2 negative cases showed a significantly better survival rate compared to the women with mutations (p<0.0001). Women from families with early onset breast cancer (<35 yrs) or bilateral breast cancer (<40 yrs) had a significantly better survival (p<0.0001) than women from families with a later age of onset.,The BRCA mutation status has a significant impact on the clinical phenotype of hereditary breast cancer which is important for the clinical management, counselling and prevention. No significant financial relationships to disclose.