"Conclusion The risk continuum for heritable cancer will become more complex as more information emerges. Unbiased population-level sequencing projects will enable the ongoing refinement of penetrance estimates and a comprehensive view of organ-specific risk. Focused investigation of the tissue-specific functional impact of risk factors, both individually and collectively, will provide information on genotype-phenotype correlations, genomic risk modifiers, and the role of the environment in modifying heritable risk. Although improvement of our risk estimations is likely achievable, no model will ever perfectly predict an “individualized” risk given the intricate interactions of biology and the environment. Continuous review of risk, combined with effective and transparent counseling, will be required to ensure that patients, their families, and their clinicians are well informed and apply the most appropriate risk Increasing Risk Increasing Risk Figure 7 Conceptualizing risk refinement and precision over time. The development of hereditary cancer risk estimation will allow for increasingly granular risk estimations over time. ACMG Statement 13 management interventions. The challenges of variant classification and estimation of penetrance are not restricted to hereditary cancer genetics and have a wide applicability to all areas of medicine. It will be important that genomic medicine services are dynamic so as to respond to the everchanging landscape of risk estimation and resulting management."