From the lab to the clinic: Lessons learned from a translational working group.

Abstract

e12576 Background: Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET), is a phase III multicenter prospective randomized clinical trial comparing the risks/benefits of active monitoring (AM) versus surgery for women with low-risk DCIS. Funded by the Patient-Centered Outcomes Research Institute, accrual opened 06/30/17 and closed 01/13/23 with 995 women enrolled. Biospecimens (blood/tissue) and breast images were collected at specified timepoints (funded by the Breast Cancer Research Foundation) and stored in central tissue/image repositories. To date, more than 90% of requested samples/images have been submitted. Methods: In 2017, the COMET Translational Working Group (TWG) was formed to facilitate the collection, submission, storage, and subsequent analysis of biospecimens/images. The TWG, consisting of clinicians, pathologists, radiologists, researchers, and patient advocates (PAs), discuss topics such as categorization of biospecimens into discovery/validation sets; development of a pathology workflow/sample tracking process; and potential areas of future research that may improve DCIS diagnostics, prognostics, and care management. Results: The TWG consists of multiple partner institutions, and team members have complementary areas of expertise/experience. While competing views may exist, consensus has been achieved in relation to major issues such as authorship, biospecimen ownership, intellectual property and criteria relevant to patient needs, through targeted discussion at monthly meetings. Logistical barriers, including data sharing and the technicalities of biospecimen release, have also been resolved through this process. The TWG has played an integral role in resolving recruitment challenges. In 2019, guidance from the TWG related to standardizing pathology eligibility criteria resulted in evidence-based protocol amendments that subsequently increased accrual. A retrospective review of biospecimens was performed to determine adequacy for ensuing correlative molecular and spatial profiling studies. PAs are integral to the TWG, assisting with logistical issues (resource requests); identifying study topics relevant to patients; providing guidance on existing (commercial) predictive/prognostic tests; promoting effective stewardship of a finite resource (tissue samples); and ensuring that the overall focus of the TWG remains firmly on advancing clinical utility. Conclusions: The COMET TWG serves the important role of overseeing biospecimen/image collection including its use and sharing. This facilitates development of research and technology that can impact the decision for surgery vs AM in women with low-risk DCIS, and ensure the translation of research findings into everyday clinical practice. Subsequent correlative science studies identified by the TWG stand to improve future DCIS pathology diagnostics, prognostics and care management.