Research from JAMA — Surveillance of BRCA1 and BRCA2 Mutation Carriers With Magnetic Resonance Imaging, Ultrasound, Mammography, and Clinical Breast Examination — ContextCurrent recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every 6 months; however, many tumors are detected at a relatively advanced stage. Magnetic resonance imaging (MRI) and ultrasound may improve the ability to detect breast cancer at an early stage.ObjectiveTo compare the sensitivity and specificity of 4 methods of breast cancer surveillance (mammography, ultrasound, MRI, and CBE) in women with hereditary susceptibility to breast cancer due to a BRCA1 or BRCA2 mutation.Design, Setting, and ParticipantsA surveillance study of 236 Canadian women aged 25 to 65 years with BRCA1 or BRCA2 mutations who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound at a single tertiary care teaching hospital between November 3, 1997, and March 31, 2003. On the day of imaging and at 6-month intervals, CBE was performed.Main Outcome MeasuresSensitivity and specificity of each of the 4 surveillance modalities, and sensitivity of all 4 screening modalities vs mammography and CBE.ResultsEach imaging modality was read independently by a radiologist and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 ductal carcinoma in situ). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. There was 1 interval cancer. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined.ConclusionsIn BRCA1 and BRCA2 mutation carriers, MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone. Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation.

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This article reviews current recommendations for breast-cancer screening and the supporting evidence, including the controversy regarding mammographic screening of women in their 40s.

Sequence-based BRCA testing can identify variants of unknown significance (VUS). Relatively little is known about how well a test outcome of VUS is understood by patients and referring physicians, and whether genetic counselors have an interest in the development of VUS management guidelines. Self-administered questionnaires were completed by 36 VUS counselees, 75 women with a BRCA mutation and 33 with no mutation found (NMF). We also surveyed 24 genetic counselors and 22 referring family physicians. One-third of VUS failed to recall the clinical significance of their result. Incorrect recall was significantly higher among VUS with high-school-only education (70% versus 19%, P = 0.02). Risk perception, cancer worry and uptake of surveillance and risk-reducing surgeries among VUS counselees were more similar to NMF than to mutation carriers. Genetic counselors accurately predicted the difficulties counselees would have with a VUS result and identified the need for VUS management guidelines. Referring physicians unanimously stated that genetic testing was indicated for unaffected siblings of VUS carriers. While VUS seems to be correctly perceived by counselees as more similar to NMF than to a pathogenic mutation, miscomprehension of VUS is more common, particularly in counselees with lower education. VUS-related educational interventions for both VUS counselees and their referring physicians are needed. We encourage the development of national VUS-related guidelines for genetic counselors.