Abstract Introduction COMET (Comparing an Operation to Monitoring, with or without Endocrine Therapy) is a phase III clinical trial randomizing patients diagnosed with low-intermediate grade DCIS to either active monitoring or surgery. The study has a planned accrual goal of 1200 patients and is enrolling until 12/31/22. The protocol requires agreement between two pathologists (who do not need to be at the same institution) that a case fulfills COMET eligibility criteria. If there is disagreement, a third pathology review is required. As per protocol, tissue blocks or unstained slides of biopsies containing DCIS from enrolled patients are sent to a designated central location. While central pathology review is not a pre-requisite of the study, a retrospective review of received materials was performed to determine adequacy for correlative molecular and spatial profiling studies. Methods Sites submit either a tissue block or twenty (20) sequentially numbered, unstained, serial five-micron tissue sections from a diagnostic biopsy of DCIS to the Alliance Foundation Trials (AFT) central biorepository, a CAP-accredited biobank. All submitted biospecimens are de-identified (coded) and investigators are blinded to arm assignment and primary study outcomes. To evaluate the adequacy of specimens for subsequent correlative science studies, one unstained slide from each submitted slide set was stained with routine hematoxylin and eosin by the biobank, scanned at 40X magnification with an Aperio scanner, and provided to one of two expert breast pathologists for adequacy review. Slides were rated as “DCIS present”, “DCIS absent”, or “possible DCIS.” To conserve tissue, submitted tissue blocks are held in abeyance pending future correlative science planning. Results As of May 2022, tissue has been submitted from 789 of 856 eligible patients enrolled in the trial, demonstrating a very high level (92%) of case submission compliance. Despite the limiting size of such lesions and general clinical center hesitancy to release blocks for clinical trial research, tissue blocks were received from 376 of 789 (48%) of cases. Among 359 cases involving slide-only submissions that have been retrospectively reviewed to date, 294 were definite DCIS (82%), 25 (7%) were classified as possible DCIS, and 40 cases (11%) were classified as no DCIS present in the section reviewed. In no case was high grade DCIS or invasive breast cancer observed. Of the cases considered possible DCIS, atypical cells were present, but the lesions were too small or incomplete to confirm DCIS. The small percentage of cases that lacked DCIS or definite DCIS could be attributed to the receipt of a different block or subsequent (deeper) section from the same block used for the initial diagnosis. These cases were previously known to the submitting institutions. Conclusion Interim analysis at 71% accrual demonstrates both the feasibility of obtaining diagnostic biopsy material of limited size and the adequacy of these samples for subsequent correlative science studies that aim to improve pathology diagnostics and patient management. Citation Format: Rachel Factor, Stuart Schnitt, Robert West, Terry Hyslop, Thomas Lynch, Deborah Collyar, Desiree Basila, Lars Grimm, Lorraine King, Jeffrey Marks, Sunil Badve, Mark Watson, Marc Ryser, Anna Weiss, Anna Rapperport, Linda McCall, H. T. Carisa Le-Petross, Ann Partridge, E Shelley Hwang, Alastair M. Thompson. Centralized adequacy assessment of ductal carcinoma in situ samples for the COMET study (AFT-25) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-13.