Background: For almost 30 years, annual mammograms for women over 40 have been a cornerstone of the US strategy to reduce breast cancer mortality. Introduction of the 2009 USPSTF screening guidelines, though based on a thorough review of the scientific literature, has triggered scientific debate and a stalemate. The solution is not to prolong the controversy with repetitious reviews of past studies, but rather to test and implement a personalized model that leverages advances in breast cancer biology, risk assessment, and imaging to provide screening recommendations based upon well-characterized measures of risk. Our WISDOM (Women Informed to Screen Depending On Measures of risk) study, a preference-tolerant randomized controlled trial funded through PCORI, will evaluate whether such a risk-based screening strategy, compared to annual screening, is as safe, is less morbid, enables prevention and is preferred by women. This upcoming pilot study will test the feasibility and technical implementation of the WISDOM trial, focusing on recruitment, enrollment, and randomization processes, a coverage with evidence development approach to enable rapid adoption, and patient experience and satisfaction. Findings will directly inform implementation of the full trial, slated to begin in fall 2015 throughout the Athena Breast Health Network, a research and care collaboration across the five UC Medical Centers and Sanford Health. Trial Design: 225 participants will be recruited from Athena patients receiving care at UCSF. Participants must be female; between age 40 and 75; have had a normal mammogram at UCSF in the past 6 months; and in the Athena research cohort. Exclusion criteria are a breast cancer or DCIS diagnosis; inability to provide consent; or inability to speak English. After education about the trial, patients will be asked if they are willing to be randomized to either the risk-based or annual screening schedule; if not, they can self-assign to their preferred schedule. The randomized and self-assigned cohorts will receive the same interventions. The risk-based screening strategy will incorporate risk assessment based on the latest Breast Cancer Surveillance Consortium model along with established and recently validated genetic risk factors, co-morbidities, and breast density, and will be used to tailor individual recommendations for starting and stopping age, frequency, and screening modality. A saliva assay will be administered to participants in the risk-based arm to screen for genetic breast cancer risk factors (BRCA1 & BRCA2 + 9 additional genes + 81 single nucleotide polymorphisms). Statistical Methods: Descriptive statistics for the proportion of women who are willing to be randomized, choose the risk-based arm in the self-assigned cohort, and are willing to accept their assigned or chosen screening schedule, as well as the distribution of participant anxiety scores, will be analyzed. This will inform statistical design for the full trial, including the number of women who should be approached to enroll 65,000 randomized participants and the sample size needed to measure anxiety and decision regret in the randomized cohort. Results from the pilot will be available September 30, 2015. Citation Format: Narasimmaraj PR, Stover Fiscalini A, Kaplan CP, van't Veer LJ, Hallada AM, Thompson CK, Theiner S, Borowsky A, Naeim A, Anton-Culver H, LaCroix A, Athena Breast Health Network Investigators, Esserman LJ. A pilot feasibility study of the WISDOM study, a preference-tolerant randomized controlled trial evaluating a risk-based breast cancer screening strategy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-10-01.