Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer

Completed

• Conditions: Familial Ovarian Cancer; Familial Breast Cancer; BRCA2-associated Malignancies; BRCA1-associate Malignancies

• Registration Number: NCT00040222
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

Individuals and families with known or suspected syndromes that include breast, ovarian or genetically-related cancers are enrolled in this family study, which is a syndrome-specific sub-set of the long-standing DCEG Human Genetics Program umbrella family studies protocol (78-C-0039). Cancer outcomes are documented through review of medical, vital, and pathology records. Selected individuals and family members are asked to complete questionnaires to assess etiologic risk factors and to undergo clinical evaluations specifically tailored to the relevant familial syndrome. Study participants are monitored prospectively for the development of outcomes of interest, typically by means of periodic mail or telephone contact. In selected instances, subjects may return to the Clinical Center periodically for study-specific follow-up examinations. Study participants are asked to donate biologic specimens to be used in the laboratory search for cancer etiology and mechanisms of carcinogenesis. DNA and serial serum samples will be collected. Tumor tissue will be obtained whenever feasible.

Clinical genetic testing for tumor susceptibility gene(s) mutations and risk notification will be offered consistent with ASCO guidelines when reasonable individual cancer risk estimates can be delivered, and only to those participants who choose to know their individual genetic status after appropriate education and counseling. The testing will be conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed laboratories. Clinical genetic testing and risk notification are entirely optional and do not affect subject eligibility for other aspects of the protocol. A separate consent procedure and consent form will be used for genetic testing and risk notification.

This protocol, developed in response to recommendations developed by the Clinical Center IRB, is intended to:

1. Provide a mechanism under which the Clinical Genetics Branch can honor the commitment made to the members of over 60 hereditary breast/ovarian cancer families which have been participated in various Human Genetics Program research studies conducted over the past 3 decades to provide genetic counseling,

clinical germline mutation testing, and consultative services now that several of the major breast/ovarian cancer susceptibility genes have been identified;

2. Provide a mechanism through which new families with various familial syndromes associated with an increased risk of breast and ovarian cancer can be studied, as research interests in these syndromes evolve over time; and

3. Create a resource of well-characterized, carefully documented high-risk families to facilitate the development of new etiologic and translational research studies in the future.

While we do not offer specific anti-cancer therapy as part of this protocol, we provide assistance to ensure that study participants who require treatment for problems that develop during the course of the study are referred to appropriate health providers. We

remain available to provide advice and consultation related to the management of the familial cancer syndrome to study participants and their health care providers.

Detailed Description

Individuals and families with known or suspected syndromes that include breast, ovarian or genetically-related cancers are enrolled in this family study, which is a syndrome-specific sub-set of the long-standing DCEG Human Genetics Program umbrella family studies protocol (78-C-0039). Cancer outcomes are documented through review of medical, vital, and pathology records. Selected individuals and family members are asked to complete questionnaires to assess etiologic risk factors and to undergo clinical evaluations specifically tailored to the relevant familial syndrome. Study participants are monitored prospectively for the development of outcomes of interest, typically by means of periodic mail or telephone contact. In selected instances, subjects may return to the Clinical Center periodically for study-specific follow-up examinations. Study participants are asked to donate biologic specimens to be used in the laboratory search for cancer etiology and mechanisms of carcinogenesis. DNA and serial serum samples will be collected. Tumor tissue will be obtained whenever feasible.

Clinical genetic testing for tumor susceptibility gene(s) mutations and risk notification will be offered consistent with ASCO guidelines when reasonable individual cancer risk estimates can be delivered, and only to those participants who choose to know their individual genetic status after appropriate education and counseling. The testing will be conducted exclusively in Clinical Laboratory Improvement Amendments (CLIA)-licensed laboratories. Clinical genetic testing and risk notification are entirely optional and do not affect subject eligibility for other aspects of the protocol. A separate consent procedure and consent form will be used for genetic testing and risk notification.

This protocol, developed in response to recommendations developed by the Clinical Center IRB, is intended to:

1. Provide a mechanism under which the Clinical Genetics Branch can honor the commitment made to the members of over 60 hereditary breast/ovarian cancer families which have been participated in various Human Genetics Program research studies conducted over the past 3 decades to provide genetic counseling, clinical germline mutation testing, and consultative services now that several of the major breast/ovarian cancer susceptibility genes have been identified;

2. Provide a mechanism through which new families with various familial syndromes associated with an increased risk of breast and ovarian cancer can be studied, as research interests in these syndromes evolve over time; and

3. Create a resource of well-characterized, carefully documented high-risk families to facilitate the development of new etiologic and translational research studies in the future.

While we do not offer specific anti-cancer therapy as part of this protocol, we provide assistance to ensure that study participants who require treatment for problems that develop during the course of the study are referred to appropriate health providers. We remain available to provide advice and consultation related to the management of the familial cancer syndrome to study participants and their health care providers.

Study Timeline

• Study First Submitted: 2002-06-22
• Study First Submitted QC: 2002-06-22
• Study First Posted: 2002-06-24
• Study Start: 2002-07-01
• Status Verified: 2024-12-11
• Last Update Submitted: 2025-03-21
• Last Update Posted: 2025-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 377

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer	Ongoing	To ascertain individuals and families at high risk of breast, ovarian andother syndromically related cancers due to known or suspected genetic factor(s) which predispose to neoplasia in order to:- Evaluate and define the clinical spectrum and natural history of disease in syndromes predisposing to familial breast/ovarian cancer;- Develop a resource of epidemiologic, 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 highrisk kindreds;- Create a biospecimen repository which will facilitate exploratory,etiologically-focused laboratory studies;- Evaluate potential precursor states of neoplastic disease in families atrisk of breast and ovarian cancer;- Quantify the risk of specific tumors in family members;- Map, clone, and determine the function of novel tumor susceptibilitygenes
Genetic and Environmental Factors	Ongoing	Identify genetic determinants, and genetic and environmental modifiers of cancer risk in individuals and families predisposed tobreast/ovarian cancer; and- Evaluate gene-gene and gene-environment interactions in thepathogenesis of familial breast/ovarian cancer.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States