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VUS Management — SCE Medical Oncology MCQ

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ModerateBreast CancerVUS ManagementSCE Medical Oncology

A 45-year-old woman undergoes genetic counselling after bilateral breast cancer diagnosis at a young age. Panel testing is negative for BRCA1/2 but identifies a BRCA2 variant of uncertain significance (VUS). How should this VUS be managed?

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Correct answer: A — A VUS should NOT be used to guide clinical management — it may be reclassified over time; clinical decisions should be based on family history and phenotype alone

Variants of uncertain significance (VUS) are identified in approximately 5-10% of genetic tests. They represent variants where there is insufficient evidence to classify as pathogenic or benign. VUS should NOT drive clinical management (risk-reducing surgery, enhanced screening, cascade family testing). Periodic review of VUS classification is recommended as new evidence may lead to reclassification. Clinical decisions should be based on family history, clinical phenotype and validated risk models (e.g. BOADICEA).

Reference: NICE CG164 Familial breast cancer; ESMO 2024 Hereditary Cancer; ACMG VUS Guidelines