Estudio de la prevalencia de mutaciones de los genes BRCAL y BRCAZ en mujeres con cáncer de mama menores de 41 años. Relación con los antecedentes oncológicos familiares y características clínico-patológicas.

Resumo

Breast cancer is the most frequent tumour in women and hereditary predisposition may contribute to it in a small subset of patients. Up 5 to 10% can be attributed to mutations in BRCA1/2. Between 1989 -1999, we selected 124 breast cancer women, diagnosed before 41 years, not selected by their family history. In this group, mutations in BRCA1/2 genes were studied. The strategy used for the analysis of BRCA1/2, was initially amplified by PCR, mutation screening through SSCP, and abnormal bands were directly sequenced. Seven patients (5.6%) were found to have pathogenic mutations: one in BRCA1 (0.8%) and six in BRCA2 (4.8%). Most pathogenic mutations (6 of 7) were located in BRCA2 (85.7%). Most mutations characterized in BRCA2 (66.7%) are located in exon 23. The patients with first degree relatives suffering from breast or ovarian cancer, or having a male relative with breast cancer were classified as "high risk". In this high risk group 4 of 26 women (15.4%) were BRCA mutation carriers, compared with 3 of 96 women (3.1%) without those previously defined familial characteristics (p=0.037). The familial history of ovarian cancer is also different between BRCA mutation carriers (37.5%) and those not harbouring any mutation (3.5%) (p=0.005). BRCA mutation carriers were diagnosed in more advanced stages of breast cancer. Several models may estimate the probability of presenting a mutation in BRCA1/2,. In our sample Myriad II and BRCAPRO, are useful to predict the presence of mutations. Considering the low frequency BRCA1/2 mutations, other currently unknown genetics factors should play an important role. These results do not make advisable a molecular study of BRCA1/2 mutations in women developing breast cancer at an early age. Familial history should be considered as the most relevant factor.