We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 b
reast and 13 ovarian cancers, two of the former also had ovarian cancer) in
a self-referral study. They were tested for germline founder mutations in
BRCA1 (185delAG, 5382insC, 188de111) and BRCA2 (6174delT). Personal/family
histories were correlated with mutation status. Logistic regression was use
d to develop a model to predict those breast cancer cases likely to be germ
line ERCA1/BRCA2 mutation carriers in this population. The most important f
actors were age at diagnosis, personal/family history of ovarian cancer, or
breast cancer diagnosed before 60 years in a first degree relative.
A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.
7%), and both cases with ovarian and breast cancer carried one of the found
er mutations. Age at diagnosis in carriers (44.6 years) was significantly l
ower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in
BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family
history of breast or ovarian cancer in first or second degree relatives. Co
nversely, 12% of non-mutation carriers had strong family histories, with bo
th a first and a second degree relative diagnosed with breast or ovarian ca
The predicted values from the logistic model can be used to define criteria
for identifying Ashkenazi Jewish women with breast cancer who are at high
risk of carrying BRCA1 and BRCA2 mutations. The following criteria would id
entify those at approximately 10% risk: (1) breast cancer <50 years, (2) br
east cancer <60 years with a first degree relative with breast cancer <60 y
ears, or (3) breast cancer <70 years and a first or second degree relative
with ovarian cancer.