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181 Background: In “window of opportunity” (WOO) clinical trials, people with newly diagnosed early-stage cancer are exposed to an experimental drug during the period of time between diagnosis and definitive anti-cancer treatment. These trials allow investigators to study drug efficacy in untreated disease, which can expedite drug development. However, for trial participants, the WOO approach requires them to decide about an altruistic clinical trial during an intense time immediately after cancer diagnosis. This qualitative study aimed to understand patient perspectives on WOO clinical trials. Methods: We recruited adults newly diagnosed with early-stage breast cancer who were awaiting definitive therapy at a single academic medical center. We developed an interview guide grounded in the theoretical framework, the Theory of Planned Behavior (TPB). TBP is a well-validated decision-making model with three domains that guide behavior: (1) attitudes (2) normative factors and (3) perceived difficulty of a behavior. We conducted one-on-one semi-structured interviews that were audio-recorded and transcribed. Transcripts were analyzed to ensure interrater reliability and content analysis was performed to assess themes that emerged. Results: We interviewed 15 women (age 32-72) with early-stage breast cancer, and the majority were White (n = 12, 80%) and at least college educated (n = 12, 80%). Key themes that emerged included favorable attitudes towards participating in a WOO trial that were altruistic, including the desire to contribute to science (n = 10, 67%) and to help future breast cancer patients (n = 5, 33%). Several individuals also identified a potential benefit to themselves (n = 10, 67%), including access to a targeted drug (n = 4, 27%) and adding meaning to their diagnosis (n = 3, 20%). However, most interviewees reported concerns about drug side effects (n = 12, 80%) and whether side effects would impact other planned treatments (n = 10, 67%). Interviewees also expressed family would be an important normative factor in decision-making (n = 8, 53%). A key theme that emerged as a difficulty was the potential delay in standard treatment (n = 14, 93%). Despite this concern, at the end of the interviews, most interviewees stated they would participate in a WOO trial if offered (n = 10, 67%). Conclusions: WOO trials are becoming increasingly common in oncology research. In this qualitative study, interviewees weighed altruism against the possibility delaying or impacting other treatments. Our results may inform trial design and communication approaches in future WOO efforts.

536Background: New breast cancer screening approaches are needed to detect clinically aggressive subtypes that may not be detected by mammography or are detected late in unscreened populations. CCG...

46 Background: Esophageal squamous cell carcinomas remains a particularly intractable disease due to limited therapeutic options as well as a lack of targeted therapies. The genetic landscape of esophageal squamous cell carcinoma is varied, but a common means of tumorigenesis in squamous cancers are alterations in copy number of putative oncogenic loci that result in upregulated mRNA. Within this subset of loci with copy number alterations, however, it has been difficult to distinguish between driver and passenger mutations using traditional in vitro models. Methods: We functionally screened a data set of amplified “outlier” candidates nominated through a bioinformatics pipeline that scored chromosomal amplifications with linked mRNA overexpression. Screening and validation was performed in a novel three-dimensional organoid model of esophageal squamous cell carcinoma that served as a tabula rasa by virtue of a single p53 null alteration. Results: Functional screening uncovered a novel oncogenic mechanism that serves to drive esophageal squamous cell cancer tumorigenesis both in vitro and in vivo when subcutaneously transplanted into immunodeficient mice. In addition, pharmacologic perturbation of this mechanism resulted in attenuation of the oncogenic phenotype in vitro. Conclusions: We have paired bioinformatics analysis of TCGA data with a p53 null organoid model to functionally validate a novel driver mechanism of esophageal squamous cell carcinoma. Studies are underway to translate these findings and hopefully generate additional therapeutic strategies for esophageal squamous cell carcinoma patients.

1010Background: A rich lymphocytic infiltrate in pre-treatment tumor biopsies predicts better overall survival (OS) in TNBC. We investigated whether peripheral lymphocyte count is similarly associa...