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Understanding the Clinical Implications of Low Penetrant Genes and Breast Cancer Risk

Opinion statement

Since the 2013 Supreme Court declaration, panel testing for hereditary cancer syndromes has evolved into the gold standard for oncology germline genetic testing. With the advent of next-generation sequencing, competitive pricing, and developing therapeutic options, panel testing is now well integrated into breast cancer management and surveillance. Although many established syndromes have well-defined cancer risks and management strategies, several breast cancer genes are currently classified as limited-evidence genes by the National Comprehensive Cancer Network (NCCN). Follow-up for individuals with mutations in these genes is a point of contention due to conflicting information in the literature. The most recent NCCN guidelines have stratified management based on gene-specific cancer risks indicating that expanding data will allow for better recommendations as research progresses. The evolving management for these genes emphasizes the clinicians’ need for evidence-based understanding of low penetrance breast cancer genes and their implications for patient care. This article reviews current literature for limited evidence genes, detailing cancer risks, association with triple-negative breast cancer, and recommendations for surveillance. A brief review of the challenges and future directions is outlined to discuss the evolving nature of cancer genetics and the exciting opportunities that can impact management.

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Correspondence to Anusha Vaidyanathan MS, CGC.

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Anusha Vaidyanathan is the Professional Issues Chair for the Texas Society of Genetic Counselors and the Research Chair for the National Society of Genetic Counselors (Cancer SIG). Both are unpaid positions.

Virginia Kaklamani has received speaker's honoraria and compensation for service as a consultant from Immunomedics, AstraZeneca, Daiichi Sankyo, Seattle Genetics, Puma Biotechnology, Pfizer, and Novartis, and has served on advisory boards for Puma Biotechnology, Radius Health, and Sanofi.

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Vaidyanathan, A., Kaklamani, V. Understanding the Clinical Implications of Low Penetrant Genes and Breast Cancer Risk. Curr. Treat. Options in Oncol. 22, 85 (2021). https://doi.org/10.1007/s11864-021-00887-4

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Keywords

  • Breast cancer
  • Low penetrance
  • Limited evidence genes
  • Cancer risks
  • Management
  • Surveillance