Wd. Foulkes et al., GERM-LINE BRCA1 MUTATION IS AN ADVERSE PROGNOSTIC FACTOR IN ASHKENAZIJEWISH WOMEN WITH BREAST-CANCER, Clinical cancer research, 3(12), 1997, pp. 2465-2469
Germ-line mutations in BRCA1 confer an increased risk of developing br
east and ovarian cancer, but little is known about the clinical course
of breast cancer in BRCA1 mutation carriers compared with noncarriers
. Two recurrent BRCA1 mutations (185delAG and 5382insC) are common (si
milar to 1.3 %) in Ashkenazi Jews and account for about 20 % of breast
cancers diagnosed before age 40 in this group, We assayed paraffin em
bedded tumor blocks from 117 unselected Ashkenazi Jewish women with pr
imary breast cancer, diagnosed before age 65 at a single institution,
for the presence of either of the two BRCA1 mutations, We reviewed the
medical records and constructed survival curves for BRCA1-positive an
d -negative subgroups. Twelve of the women (10.3%) were found to carry
BRCA1 mutations (eight mutations were 185delAG, and four were 5382ins
C), The probability of death from breast cancer in the first 5 years w
as 35.7% in the BRCA1 mutation-positive group and 4.3% in the 100 wome
n without a mutation (P = 0.0023). The 5-year distant disease-free sur
vival was 68.2% in BRCA1 mutation carriers and 88.7% in noncarriers (P
= 0.019). These data suggest that breast cancer occurring in an Ashke
nazi Jewish woman carrying a germ-line BRCA1 mutation has an adverse p
rognosis, This information is available before the diagnosis of breast
cancer, and therefore, this finding may have important implications f
or prevention of breast cancer in BRCA1 mutation carriers.