Trial Information

Risk of Breast Cancer and Hyperplastic Conditions in the Breast Cancer Serum Bank in Relation to Inherited Genetic Variants

Prevention and treatment of intraepithelial neoplasia and benign pre-malignant conditions
has become an important focus of the NCI's 2015 goal of eliminating suffering and death due
to cancer, although very little is known about the factors that influence development of
frank malignancy in those with high risk benign/precursor conditions. The Radiation
Epidemiology and Biostatistics Branches of the NCI propose to evaluate the contribution of
inherited genetic variation to benign pre-malignant breast conditions, and to subsequent
breast cancer risk in women diagnosed with such conditions, in the Breast Cancer Serum Bank,
a unique biospecimen resource housed at NCI since 1995. Premenopausal participants (N=2632)
biopsied at an average age of 27 in 1977-1987, (many diagnosed with high risk benign breast
conditions (moderate/florid breast hyperplasia and atypia)) were interviewed and provided a
blood sample. Participant biopsy reports will be obtained for review and recoding, and
participants will be traced for vital status and breast cancer development (expected n = 240
cases). Variants in genes related to hormone metabolism and cell signaling, processes
implicated in the development of premalignant breast conditions, and in genes associated
with cell cycle control and apoptosis, and thus possibly related to progression to breast
cancer among women with premalignant breast conditions will be assessed at the NCI Central
Genotyping Facility. We have a remarkable opportunity in this study to address scientific
questions regarding breast carcinogenesis mechanisms at relatively little cost. Greater
comprehension of the influence of inherited factors on distinct steps in the biological
pathway, first from normal tissue to benign high risk breast tumors, and then hence the
breast cancer, should contribute to our understanding of the molecular mechanisms that shape
breast cancer development, and holds promise for the discovery and delivery of sound
risk-adapted interventions for women with high risk premalignant conditions.