||5R01CA072025-04 Interpret this number
||Etiology of Early Breast Malignancy
The development of malignancy in the human breast is a poorly understood
process. It is clear, however, that the occurrence of in situ cancers,
particularly ductal carcinoma in situ (DCIS), is an important step in the
evaluation of some invasive breast cancers. The investigators propose to
elucidate t he occurrence, biological features, and etiology of in situ and
invasive breast cancers, with a particular focus on ductal carcinoma in
situ (DCIS) . They will identify 560 new cases of in situ breast cancer
diagnosed over a four-year period in New cases of in situ breast cancer
diagnosed over a four-year period in New Hampshire and Vermont, using
mammography cell tumor registries in these two states, review of all breast
biology reports, and link to the state cancer registries. Of these cases,
they expect to enroll 412 women of age 75 or less and to classify their
biopsies into histopathological categories of DCIS, using a standard
format. Using population data sources, they also will enroll a random
sample of 412 women with invasive breast cancer. They will obtain tissue
blocks for all 824 invasive and in situ cases for immunohistochemical
staining to measure HER-2/neu, p53, estrogen receptor (ER) and progesterone
receptor (PR) protein expression. Blocks will be analyzed, using PCR
techniques, for the alteration of cancer-related genes p16 and p15 on
chromosome 9p, and for extent and frequency of loss of heterozygosity on
chromosome 11. As a control, they will identify 412 women without breast
malignancy, using the same network resources. By telephone questionnaire,
they will assess demographic characteristics, hormones use, and
reproductive and lifestyle risk factors for cases and controls.
Statistical analyses will assess: (1) the age-specific incidence of in
situ breast cancer and its cell types; (2) the prevalence of
immunohistochemical and molecular biological markers among in situ and
invasive cancers; (3) risk factors for DCIS and its subtypes of (e.g.,
with or without comedo features: (4) possible associations, within the
entire spectrum of breast neoplasia, between risk factors and (a) HER-
2/neu, p53, ER and PR expression,and (b) chromosomal deletions. They will
use these analyses to assess the possibility that breast cancer arises
through multiple distinct causal pathways and that, in fact, breast cancer
represents a heterogenous group of etiologic entities. The investigators
point out that studies of this type will help to classify breast cancers
into etiologically relevant categories, leading eventually to the
identification of specific modifiable risk factors.
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