Hereditary cancer multigene panel testing in the United States and Europe: real-world constraints and implications...

Multigene panel testing has become an important component of hereditary cancer evaluation in Western practice. This shift has been driven by advances in next-generation sequencing, declining costs, and the increasing relevance of germline findings to treatment, surveillance, prevention, and cascade testing. In Japan, publication of The Japanese Society for Hereditary Tumors Guidance: Hereditary Cancer Syndromes with Multigene Panel Testing, 2025 Edition provided a timely framework for reconsidering how Western experience should inform domestic implementation. Evidence from the United States and Europe has fostered the view that multigene panel testing has replaced sequential single-gene testing as a first-line approach because of its broader diagnostic yield and growing use in routine care. However, broader detection does not automatically translate into broader clinical benefit. Multigene panel testing is most valuable when the pathogenic variants detected are sufficiently prevalent, highly penetrant, and linked to established surveillance, risk-reducing surgery, targeted therapy, or cascade testing. Broader panels may also increase variants of uncertain significance, psychological burden, and unnecessary management. This review examines why multigene panel testing came to be seen as a first-line approach, distinguishes diagnostic yield from meaningful clinical utility, and considers why Western adoption should inform Japanese practice not as a mandate for indiscriminate expansion, but as support for phased, quality-assured, utility-oriented integration.