Abstract Introduction and Background: Mammography is thought to have an overall sensitivity of 87% according to the Breast Cancer Screening Consortium (BCSC). However, evidence from more recent studies indicate that a significant proportion of patients come into care with breast cancer symptoms, which trigger diagnosis rather than regular screening mammography. Women with breast cancer symptoms often have advanced cancer at diagnosis. This implies that previous negative mammograms are false negatives, and that screening mammography alone was insufficient for this population. Such populations include women with dense breasts, for whom mammography has a known 10-29% decrease in regardless of stage at diagnosis, and women who do not use screening mammography regularly or at all. Specific Experimental Aims: In a US population-based cohort of women who have developed first time breast cancer, we will 1) determine the variance in mode of detection, and 2) determine if mode of detection varied by breast density or by stage at diagnosis. Methods and Design: We identified a cohort of 386 women with a diagnosis of first time breast cancer (ICD codes) within a 7 county, 98.5% coverage population. We randomly sampled 30 women and performed chart review. The data were collated in REDCap, and reported with descriptive statistics. Results: In our pilot random sample (n=30), 33% (10/30) of women had DCIS, 30% (9/30) had non-advanced cancer, and 37% (11/30) had advanced cancer. For women with DCIS, 90% (9/10) were found with screening mammography, compared to only 44% (4/9) of non-advanced, and 45% (5/11) advanced cancers. Approximately 43% (13/30) of women in this sample had dense breasts. Interestingly, 61.5% (8/13) women with dense breasts, and 62.5% (10/16) of women with non-dense breasts had screening mammography as the mode of detection. Finally, among women with dense breasts, 46.1% (6/13) had DCIS, 30.8% (4/13) had non-advanced cancer, and 23.1% (3/13) had advanced cancer, while for women with non-dense breasts, 25% (4/16) had DCIS, 31.2% (5/16) had non-advanced cancer, and 43.8% (7/16) had advanced cancer. Conclusions and Future Directions: These pilot data suggest that our population reflects both the breast density rate (47%, BCSC) and the rate of advanced cancers (36%, SEER) found in the national population, and that there is a strong likelihood that regardless of breast density, but especially for non-DCIS, screening mammography alone may not be sufficient detect breast cancer (44-45%) compared to the BCSC statistic of 87%. This may be due to misattribution of mode of detection for breast cancer, especially in symptomatic later stages of disease. Once the full study is completed, future research regarding outcomes (mortality and otherwise) and stage at diagnosis for patients who use additional screening methods may be valuable. In addition, for women with lower access to, or who choose not to use screening mammography, future research regarding revisiting the use of SBE and CBE as well as other modalities may also be valuable. Citation Format: Susanna N Basappa, Lila JF Rutten. Variance in mode of detection for breast cancer by breast density and stage at diagnosis: A pilot study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C099.