Detection of VHL variant on multigene panel testing for hereditary breast cancer: Implications for genetic counselling

Abstract

As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breast cancer who harboured a secondary finding in the VHL gene variant without other cancer risk alleles (e.g., BRCA1/BRCA2) sufficient to explain her primary presentation. Subsequent exam revealed ophthalmic manifestations of von Hippel-Lindau syndrome (VHLS), emphasizing the importance of multidisciplinary clinical assessment and phenotyping. The development of retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumours and phaeochromocytomas are characteristic of VHLS, but the link with breast cancer is poorly understood. Though the benefit of hereditary cancer genetic testing is well-known, this case highlights the importance of pre-test genetic counselling to prepare patients for all possible results, including additional unanticipated genetic diagnoses. Such pre-test counselling can set appropriate expectations for the possible requirement of ongoing surveillance and/or treatment.