For familial breast cancer, this corresponds to a cumulative risk of breast cancer at age 70 years in CHEK2*1100delC heterozygotes of 37% (95% CI, 26% to 56%), which compares with similar previous estimates of 57% (95% CI, 47% to 66%) for BRCA1 mutation heterozygotes and 49% (95% CI, 40% to 57%) for BRCA2 mutation heterozygotes.
Loss of heterozygosity (LOH) was analysed in 84 primary tumours from sporadic, familial and hereditary breast cancer using five microsatellite markers spanning the chromosomal region 13q12-q13 which harbours the BRCA2 breast cancer susceptibility gene, and using one other marker located within the RBI tumour-suppressor gene at 13q14.
In particular, the identification of the breast cancer susceptibility genes BRCA1 (breast cancer gene 1) and BRCA2 and the current genetic testing for mutations in both genes are the basis for estimating disease risks for women with a strong family history of breast cancer and will provide important information on the prevention and treatment of familial breast cancer.
The high incidence of mammary tumor disease reported in certain canine breeds suggests a significant genetic component, as has already been described in human familial breast cancer-in BRCA1- and BRCA2-associated breast cancer in particular.
The frame-shifting mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene (CHEK2) has been reported to be associated with familial breast cancer in families in which mutations in BRCA1 and BRCA2 were excluded.
As PALB2-deficient tumors were shown to be sensitive to Poly(ADP-ribose) Polymerase (PARP) inhibitors, our study has implications for newly developed, favorable treatment options in familial breast cancer.