Abstract Background: Ashkenazi Jews have a 1 in 40 prevalence of carrying a BRCA1/2 mutation, mainly due to 3 founder mutations. Prior literature suggests that population-based genetic testing among Ashkenazi Jews is cost-effective and may detect over 50% more mutation carriers than family history-based screening. Orthodox Jewish women are an understudied population with unique social, cultural, and religious factors that may influence BRCA genetic testing. The aim of our study was to examine factors associated with BRCA genetic testing intention/uptake among the Orthodox Jewish community. Methods: A one-time online survey was distributed to Orthodox Jewish women by 3 shuls from Washington Heights, NY (53% response rate) and through additional referrals. The questionnaire obtained information regarding demographics, breast cancer risk factors, genetic testing knowledge, decision self-efficacy, perceived breast cancer risk, breast cancer worry, and religious and cultural factors affecting medical decision-making. The Tyrer-Cuzick model was used to calculate lifetime breast cancer risk and accurate risk perception was defined as within +/-10% of actual lifetime risk. Descriptive statistics and multivariable logistic regression models were used to identify independent predictors of genetic testing intention/uptake. Results: Among 342 evaluable participants, median age was 26 years (range, 19-77); 92% were Ashkenazi and 8% Ashkenazi/Sephardi; 98% had a college education, including 47% with post-graduate degrees. Despite being highly educated, only 54% of women had adequate genetic testing knowledge. Median lifetime breast cancer risk was 16% (range, 2.3-60.9) and only 44% had accurate breast cancer risk perceptions. Although 48% had a family history of breast cancer and 16% had a relative that tested positive for BRCA1/2 mutation, only 5% had undergone BRCA testing while 48% had the intention of undergoing genetic testing. Higher lifetime breast cancer risk, high decision self-efficacy regarding genetic testing, overestimation of breast cancer risk, and increased breast cancer worry were associated with genetic testing intention/uptake. The most important factors in the decision to have BRCA testing were to help prevent dying of cancer (55%), to help prevent getting cancer (54%), and effect on children (40%). Multivariable analysis of factors associated with BRCA genetic testing intention/uptake OR95% CIp-valueDecision Self-Efficacy (range, 0 [not confident] - 4 [very confident])1.41.02-1.980.038Actual Lifetime Breast Cancer Risk (range, 0 - 100%)1.11.03-1.100.0005Accuracy in Breast Cancer Risk Perception Accurate (referent)1.0--Underestimate1.20.50-2.850.691Overestimate2.61.45-4.610.001Breast Cancer Worry (range, 1 [none] - 7 [worry all of the time])1.51.18-1.980.001 Conclusions: By understanding the religious and cultural issues regarding genetic testing in the Orthodox Jewish community, we can develop targeted interventions designed to enhance decision self-efficacy and improve accuracy of breast cancer risk perceptions to decrease unnecessary worry. This may in turn increase informed decision-making about BRCA genetic testing and implementation of cancer prevention strategies among Ashkenazi Jews. Citation Format: Trivedi MS, Tang EY, Kukufka R, Chung WK, David R, Respler L, Leifer S, Schechter I, Crew KD. Factors associated with BRCA genetic testing intention and uptake among Orthodox Jewish women. [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 P2-09-23.