Objective: To assess the outcome of accelerated patient surveillance in patients at high risk for inherited breast or ovarian cancer. Methods: Using stringent inclusion criteria, 57 high-risk patients (7 positive for BRCA1/2 mutations, 39 mutation negative, and 11 unaffected) were recruited from a genetic testing protocol for inherited breast/ovarian cancer and were followed for 5 years (192.5 total patient years). Patients received twice annual physical examinations, imaging studies, measurement of CA125 and CA15-3, psychometric measurements, and unstructured interviews by a psychologist. Results: When mutation (+) and mutation (-) patients were compared, there were no significant differences in the development of disease metastasis, recurrence, or new cancers. No unaffected patients developed cancer. Management of osteoporosis, sexual function, and psychological distress were major concerns. Conclusions: Our data suggest that all patients with remarkable family history, regardless of their mutation status, may be at substantially increased risk for disease progression and development of new cancers, which is often not ovarian or recurrent breast cancer. Although prophylactic surgery is important in decreasing cancer recurrence in mutation carriers, increased surveillance with physical examinations and psychological support is also valuable and acceptable to such high-risk patients.

Over the average lifetime, one in eight women will be affected with breast cancer. Because of the common nature of this disease, many women may give a history of an affected family member. An estimated 5 to 10% of affected patients may have inherited a mutation in a gene that predisposes them to the development of breast cancer.1 Two such genes, BRCAl and BRCA2, have been well characterized and may account for 60 to 80% of cases of inherited breast cancer and 80 to 90% of cases of inherited breast/ovarian cancer.2 Mutations in BRCAl are associated with a 60 to 85% lifetime risk for the development of breast cancer and a 25 to 45% risk for the development of ovarian cancer;2·3 mutations in BRCA2 are also associated with a 75 to 85% risk for breast cancer development and an 11% risk for ovarian cancer.4 Approximately 3 to 14%of cases of male breast cancer, particularly if a family history of breast cancer is present, may be attributed to BRCA2 mutations.5 Nationwide, the estimated proportion of all cancer diagnoses by age 80 years, which are a result of germ-line BRCAl mutations, is 3.0% for breast cancer and 4.4% for ovarian cancer.6 Mutations in other genes, such as ataxia-telangiectasia, pTEN (breast and thyroid cancer), and H-ras, have also been associated with the development of breast cancer, although their characterization and dis ease development status is less clear. Undoubtedly, numerous other genes, yet undescribed, are also involved in inherited breast cancer.

Testing for BRCAl and BRCA2 mutations is available commercially. Although the long-term benefits of mutation identification are still under investigation, it is hoped that such identification will heighten vigilance for disease detection and will provide important information for families. The Familial Breast and Ovarian Cancer Research Project at Keesler Air Force Base (Mississippi) and Madigan Army Medical Center (Tacoma, WA; funded by Department of Defense/Health Affairs Breast Education and Awareness Project) was designed to develop a comprehensive approach for such patients, including the formation of educational materials, counseling approaches, and testing and follow-up guidelines. Testing methods, the outcomes of testing, and general guidelines for patient management have previously been reported.7,8 This article details the outcome of accelerated surveillance of patients who were identified through the testing protocol to be at high risk for new or recurrent disease based on their family history or the presence of a diagnosed BRCAl or 2 mutation.

Subjects and Methods

Patients were recruited from an Institutional Review Boardapproved protocol for inherited breast/ovarian cancer at Keesler Air Force Medical Center, Keesler Air Force Base and Madigan Army Medical Center for a separate Institutional Review Boardapproved Phase II surveillance study. The project was initiated in May 1997, with genetic testing offered through May 1999, when funding for testing was lost. The total study period was from May 1997 to May 2002. The patients were self-referred or were referred by their primary physician to the research project. They received extensive genetic counseling, pedigree analysis, records verification, and mutation risk prediction using the Couch model9, and they were offered genetic testing for BRCAl or 2 mutations if they met protocol guidelines and entered the project in the first 2 years (Table I). Patients unaffected with breast or ovarian cancer were not offered genetic testing unless there was a known BRCAl or 2 mutation in their family; however, because of the extreme anxiety of such patients, they were considered eligible for accelerated surveillance if they had at least one first-degree and one second-degree relative with breast or ovarian cancer.