DESCRIPTION (Adapted from the Applicant's Abstract): Approximately 12 percent
of Ashkenazi Jewish women with breast cancer are carriers of mutations in one
of two cancer susceptibility genes, BRCA1 and BRCA2. Both of these genes are
associated with a very high lifetime risk of breast cancer (estimated to be
between 57 percent and 90 percent). It is important to know if the natural
history of hereditary breast cancer is different from non-hereditary breast
cancer. BRCAl-associated breast cancers are typically of high grade, are
estrogen and progesterone receptor negative, and are p53-mutation positive. All
of these are adverse prognostic features. The purpose of the present study is
to estimate the ten-year survival rate for breast cancer patients with BRCA1
and BRCA2 mutations, and to compare this to women without mutations. To do
this, we will identify and evaluate 2,818 cases of breast cancer diagnosed in
Israel in 1987 and 1988. Approximately 1,900 of these cases occurred in
Ashkenazi Jewish women. These women were reported to the Israel Cancer Registry
from 21 source hospitals throughout the country. We will obtain breast cancer
tissue blocks, or precut slides, from the affiliated pathology departments. DNA
samples extracted from the tumour specimens will be typed for three founder
Jewish mutations in BRCA1 and BRCA2. We will obtain clinical information about
tumour size and nodal status at diagnosis. We will obtain demographic
information about the year and place of birth of the patient and her religion
and ethnic group. We will obtain current vital status, and if dead, year and
cause of death. We will estimate the ten year survival rate for hereditary
breast cancer and compare this with that for non-hereditary cases. We will
compare survival rates for BRCA1 and BRCA2 carriers separately. We will also
study the influence of BRCA1/BRCA2 mutations in the subgroup of lymph-node
negative breast cancers.
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