Trial Information

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

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.