Grant Number:	5R01CA080978-03 Interpret this number
Primary Investigator:	Narod, Steven
Organization:	University Of Toronto
Project Title:	The Natural History of Hereditary Breast Cancer
Fiscal Year:	2002

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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