Abstract ES3-2: Sooner or later: considering risk over time, and implications for management
Authors: Khan SA 
Published: March 2020

Abstract
Cancer risk management revolves around the following important areas: genetic evaluation, surveillance recommendations, risk-reducing options, and lifestyle modification. Aspects of time are important for all of these areas, with the possible exception of lifestyle modification. For genetic evaluation, age at onset of affected individuals is a key parameter. Decisions about surveillance and risk-reducing strategies are based on age, and time-dependent estimates of cancer risk, with the most commonly-used time-frames being 5 years, 10 years, and remaining lifetime (to age 85 or 90). However, little attention is generally given to the time-frame of the benefit. For example, surveillance recommendations are based on lifetime risk when in fact the benefit (as defined by cancer detection success) cannot exceed the lead-time of the test. On the other hand, risk reduction (particularly with medication) is often presented based on risk estimated over the next 5 years. As more women are designated high risk, given increased prevalence of MRI surveillance and subsequent biopsies, and increased use of genetic testing with identification of moderate penetrance genetic variants, the question of risk thresholds that should be used for recommendations related to risk management become increasingly important. Surveillance recommendations: Remaining lifetime risk (RLR) estimates for women in their 40s generally project over 40 years or more. However, validation of these very long-term projections remains questionable, and validation is most robust for the 10-year time-frame (PMID 25956172). The lead-time gained with MRI surveillance has been estimated at 1-2 years for carriers of BRCA 1/2 mutations, and 4 years for non-carriers with positive family history of breast cancer (PMID 25820931) The predicted mean preclinical detectable phase (i.e. the time during which a cancer is screen-detectable) is estimated to be 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2 (PMID 22744338). Similar estimates for non-carrier women at increased familial risk are unlikely to be longer than 10 years. Therefore, given the greater reliability of 10-year risk estimates, it appears most reasonable to make recommendations for intensified screening based on 10-year risk rather than RLR. Recommendations for use of risk-reducing medications (RR-meds): In contrast to screening, have been made to non-carrier high risk women based on 5-year risk estimates of 1.7% or greater. Acceptance of medications has been low for a variety of reasons, one of which is the seemingly small risk conveyed by a 5-year risk estimates. Here, it would seem reasonable to extend the time-frame over which risk is calculated, since the protective benefit of tamoxifen is known to extend to ~15 years, and is likely to be in the same range for aromatase inhibitors. New ASCO guidelines on use of RR-meds now includes 10-year estimates of 3% with the NCI BCRAT, or 5% with the Tyrer-Cuzick. In summary, the use of 10-year risk estimates would simplify the management counseling of women at increased risk of breast cancer for both practitioner and patient, and place it on a better evidence base than the use of RLR or the 5-year interval.
Citation Format: SA Khan. Sooner or later: considering risk over time, and implications for management [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES3-2.