Grant Details
Grant Number: |
3R01CA070923-05S1 Interpret this number |
Primary Investigator: |
Worsham, Maria |
Organization: |
Henry Ford Health System |
Project Title: |
Benign Breast Disease-Molecular Differentiation of Risk |
Fiscal Year: |
2001 |
Abstract
DESCRIPTION: (Adapted from Investigator's Abstract) Although the risk of
breast cancer for women in the U.S. is approximately 1 in 9, identification
of risk factors and translation of that knowledge into strategies for
prevention have been inhibited by poor understanding of disease
pathogenesis. A few benign breast proliferations are associated with higher
risk of breast cancer but definition of a preneoplastic morphologic
continuum is lacking. The investigators propose to study 5353 eligible
women, derived from a large multi-ethnic population, diagnosed by biopsy
with benign breast disease between 1981-1991, followed from 5-15 years, and
yielding an estimated 248 women who will have developed invasive breast
cancer. The overall aims are to 1) ascertain the incidence and time span of
breast cancer development in this cohort, 2) to estimate the frequency of
selected genetic alterations in both benign breast disease (BBD) and
invasive cancers from the same individuals in a subset of the cohort and 3)
using a nested case-control approach, to evaluate risk factors for breast
cancer among women with BBD, including specific histological
characteristics, molecular markers, family history of breast cancer, and
reproductive history.
The purpose of the study is to evaluate the importance of biomarkers for
risk for breast cancer development and determination of their contribution
to definition of a genetic sequence in breast carcinogenesis.
Assessment of genetic alterations will employ florescent in situ
hybridization and the polymerase chain reaction (PCR). The PI will identify
chromosomal aneuploidy, selective with respect to individual chromosomes and
as a measure of DNA ploidy, and HER-2/neu amplification patterns in BBD and
invasive cancer. The PI will identify p53 mutations by single strand
conformation analysis (SSCP), determine clonality using the PCR nested
primer approach for the PGK locus (on Xq arm), and assess loss of
heterozygosity (LOH) for intragenic markers of the BRCA1 (17q21) and
E-cadherin (16q22) genes. When LOH is observed, analysis of the genes using
SSCP will attempt to identify the putative mutations. Lack of a
constitutional BRCA1 mutation will rule out one form of inherited breast
cancer, allowing subtyping of the remaining tumors by histopathological and
genetic profiles, and time frame of cancer development. This study should
help establish a genetic and morphologic continuum from BBD to breast cancer
and provide a firmer basis for interpretation of the roles of known risk
factors, with the eventual objective of permitting targeted testing of
preventive strategies and therapeutic regimens.
Publications
None. See parent grant details.