Study of Individuals and Families at High Risk for Breast or Ovarian Cancer

OBJECTIVES:

- Evaluate and define the clinical spectrum and natural history of disease in syndromes
predisposing to familial breast/ovarian cancer.

- Develop a resource of epidemiological, clinical, behavioral, and genetic information on
individuals and families predisposed to familial breast/ovarian cancer.

- Track and validate cancer occurrence and other clinical outcomes in members of these
high-risk kindreds.

- Evaluate potential precursor states of neoplastic disease in families at risk of breast
and ovarian cancer.

- Quantify the risk of specific tumors in family members of this high-risk population.

- Map, clone, and determine the function of novel tumor susceptibility genes in this
high-risk population.

- Identify genetic determinants and genetic and environmental modifiers of cancer risk in
individuals and families predisposed to breast/ovarian cancer.

- Evaluate gene-gene and gene-environment interactions in the pathogenesis of familial
breast/ovarian cancer.

OUTLINE: Individuals undergo a clinical evaluation that may include a medical history and a
physical examination, including possible pelvic or prostate exam. Women may also undergo
mammography, MRI of the breast, CA 125 level, transvaginal color doppler, and breast duct
lavage. Men may also have a serum PSA obtained if they are over 50 years of age and a breast
duct lavage and breast imaging if there is a personal history or risk of familial breast
cancer. Some individuals may undergo excisional or needle biopsies or other diagnostic
procedures (e.g., galactography or ductal endoscopy) to evaluate a suspected diagnosis of
breast, ovarian, or other cancers.

Biologic specimens that may be collected include blood for germline DNA extraction, buccal
cells, tumor tissue, and/or skin fibroblasts.

One family member completes a family history questionnaire. Family members may complete
psychological assessments.

Some individuals may undergo genetic testing and counseling.

Families are contacted approximately every year for follow-up information.

A certificate of confidentiality protecting the identity of research participants in this
project has been issued by the National Cancer Institute.

PROJECTED ACCRUAL: A total of 500 participants will be accrued for this study.