• Clinical spectrum and natural history of disease in syndromes predisposing to familial breast/ovarian cancer by clinical and laboratory data collected from study families as sufficient numbers of new families are accrued
• Develop a resource of epidemiologic, clinical, behavioral, and genetic information on individuals and families predisposed to familial breast/ovarian cancer by using medical and family history questionnaires, history and physical examinations, system ...
• Cancer occurrence and other clinical outcomes in members of these high-risk kindreds by medical and family history questionnaires, history and physical examinations, systematic documentation and confirmation of reported cancers
• Create a biospecimen repository to facilitate exploratory, etiologically-focused laboratory studies by systematic collection and preservation of serum, plasma, whole blood, DNA, EBV-transformed lymphoblastoid cell lines, normal and tumor tissue obtai ...
• Potential precursor states of neoplastic disease in families at risk of breast and ovarian cancer by systematic collection and histopathologic evaluation of breast, ovary, and fallopian tube tissue
• Prospective risk of specific tumors in family members by systematic follow-up of study participants, objective confirmation of reported cancers, and documentation of vital status by using variations on life table analysis and standardized incidence ...
• Function of novel tumor susceptibility genes by collecting and storing DNA from extended families, both BRCA1/2 mutation-positive and mutation-negative
• Identify genetic determinants, and genetic and environmental modifiers of cancer risk in individuals and families predisposed to breast/ovarian cancer by medical and epidemiologic data acquired from questionnaries
• Evaluate gene-gene and gene-environment interactions in the pathogenesis of familial breast/ovarian cancer by combining epi, genetic risk factor data with results of mutation testing (various strategies, including candidate gene testing, single nucl ...

RATIONALE: Studying individuals and families at high risk for breast or ovarian cancer may help in identifying the genes involved in the development of breast and ovarian cancer and help to identify other persons at risk for cancer.

PURPOSE: Study to identify genetic, behavioral, and environmental factors related to cancer risk in 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.

• Breast Cancer
• Hereditary Breast/Ovarian Cancer (brca1, brca2)
• Ovarian Cancer

• Genetic: gene mapping
• Genetic: mutation analysis
• Other: questionnaire administration
• Procedure: biopsy
• Procedure: breast duct lavage
• Procedure: breast imaging study
• Procedure: magnetic resonance imaging
• Procedure: radiomammography
• Procedure: study of high risk factors

• McInerney-Leo A, Hadley D, Kase RG, Giambarresi TR, Struewing JP, Biesecker BB. BRCA1/2 testing in hereditary breast and ovarian cancer families III: risk perception and screening. Am J Med Genet A. 2006 Oct 15;140(20):2198-206.
• Kramer JL, Velazquez IA, Chen BE, Rosenberg PS, Struewing JP, Greene MH. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol. 2005 Dec 1;23(34):8629-35.
• McInerney-Leo A, Biesecker BB, Hadley DW, Kase RG, Giambarresi TR, Johnson E, Lerman C, Struewing JP. BRCA1/2 testing in hereditary breast and ovarian cancer families II: impact on relationships. Am J Med Genet A. 2005 Mar 1;133(2):165-9.
• McInerney-Leo A, Biesecker BB, Hadley DW, Kase RG, Giambarresi TR, Johnson E, Lerman C, Struewing JP. BRCA1/2 testing in hereditary breast and ovarian cancer families: effectiveness of problem-solving training as a counseling intervention. Am J Med Genet A. 2004 Oct 15;130(3):221-7.
• Biesecker BB, Ishibe N, Hadley DW, Giambarresi TR, Kase RG, Lerman C, Struewing JP. Psychosocial factors predicting BRCA1/BRCA2 testing decisions in members of hereditary breast and ovarian cancer families. Am J Med Genet. 2000 Aug 14;93(4):257-63.
• Loud JT, Weissman NE, Peters JA, Giusti RM, Wilfond BS, Burke W, Greene MH. Deliberate deceit of family members: a challenge to providers of clinical genetics services. J Clin Oncol. 2006 Apr 1;24(10):1643-6. No abstract available.
• Mateus Pereira LH, Sigurdson AJ, Doody MM, Pineda MA, Alexander BH, Greene MH, Struewing JP. CHEK2:1100delC and female breast cancer in the United States. Int J Cancer. 2004 Nov 10;112(3):541-3. No abstract available.
• Struewing JP, Hartge P, Wacholder S, Tucker MA, Greene MH. BRCA1 and sex ratio. Eur J Hum Genet. 2004 Aug;12(8):663-7.
• Wacholder S, Struewing JP, Hartge P, Greene MH, Tucker MA. Breast cancer risks for BRCA1/2 carriers. Science. 2004 Dec 24;306(5705):2187-91; author reply 2187-91. No abstract available.
• Rutter JL, Smith AM, Davila MR, Sigurdson AJ, Giusti RM, Pineda MA, Doody MM, Tucker MA, Greene MH, Zhang J, Struewing JP. Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from breast-ovarian cancer families and among early-onset breast cancer cases and reference individuals. Hum Mutat. 2003 Aug;22(2):121-8.
• Gail MH, Greene MH. Gail model and breast cancer. Lancet. 2000 Mar 18;355(9208):1017. No abstract available.

DISEASE CHARACTERISTICS:

• Any of the following:

  • Families with neoplasias of an unusual type, pattern, or number, including breast cancer, or which is consistent with an identified or suspected familial cancer syndrome, including breast and/or ovarian cancer

  • Families with a history of any of the following types of syndromes:

    • Familial breast/ovarian
    • Li-Fraumeni
    • Peutz-Jegher
    • Cowden
  • Families with multiple cases of breast cancer among first- and second-degree relatives
  • Families with a history of other cancers that do not fit into a well-characterized syndrome (e.g., multiple occurrences of breast and colorectal cancers)
  • Families of an individual with a known mutation in the BRCA1 or BRCA2 gene
  • Individuals with a personal history of neoplasia(s) or benign conditions of an unusual type

  • Individuals with unusual demographic features, including:

    • Young age at onset of disease
    • Multiple primary sites
    • Rare tumor type of pathologic characteristic
• At least 2 living affected family members are required for known or suspected familial syndromes for which no gene has been identified
• Diagnoses must be verifiable

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified