Abstract PS3-03-08: Initial results from RECAST DCIS: Multicenter platform trial testing active surveillance and novel endocrine therapy agents for DCIS management

Abstract Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous, non-invasive condition characterized by the proliferation of malignant epithelial cells within the duct, with variable risk of progression to invasive disease. Current standard treatment involves surgical resection followed by possible adjuvant endocrine therapy and/or adjuvant radiation. However, a substantial proportion of DCIS may never progress to invasive disease and thus may be overtreated with the current standard of care. Consequently, active surveillance (AS) is emerging as a treatment option for patients with DCIS. DCIS is definitely a risk factor for breast cancer, and should be reframed as an opportunity for preventive intervention. RECAST (Re-evaluating Conditions for Active Surveillance Suitability as Treatment) is a Phase II adaptive platform trial studying the efficacy of up front endocrine therapy to identify appropriate candidates for long-term active surveillance versus those who would benefit from standard surgical treatment. Patients with hormone receptor positive DCIS of any grade undergo baseline breast MRI and are randomized to one of four hormonal therapy regimens, including standard endocrine therapy, z-endoxifen, elacestrant or HAV-008 with the potential to offer equivalent or improved benefit with less adverse effects. Serial MRI at 3 and 6 months is then used to evaluate change in background parenchymal enhancement (BPE) and DCIS lesion. Patients deemed low risk based on imaging response have the option to continue AS and avoid surgery and radiation and continue their endocrine therapy for 3 years. The primary endpoint of the trial is to determine whether novel endocrine therapy increases the fraction of patients who will be suitable for long-term AS as measured by the fraction of patients who remain on active surveillance at 7 months compared to control. To date, over 50 patients are enrolled in the trial. Our target accrual of 400 patients. A total of 17 (34%) patients have reported an AE, all grade 1 or 2, with no serious adverse events reported and no safety signals identified. Of the 50 patients currently on treatment, 25 have reached or gone beyond the 6-month mark and 22 (88%) of those patients remain on active surveillance with a median follow up of 351 days. At the 3 month point, one patient progressed on imaging and two chose to come off surveillance due to other reasons. At 6 months, 8% (2/25) progressed on imaging and one additional patient has proceeded to surgery at the 1 year point. One patient who went on to have surgery was found to have invasive disease (pT1bN0). Robust accrual continues at sixteen currently active sites with five more sites anticipated to open in the next few months. The shift to using hormonal therapy in the neoadjuvant setting allows investigators to assess response to endocrine therapy, characterize risk of progression to invasive cancer and helps to better inform treatment-making decisions before continuing AS or proceeding with surgery, and appropriately assesses the value of endocrine risk reduction prior to surgery to avoid it. The trial uses a patient-centered approach and gives all patients a window of opportunity to assess their response as well as medication tolerability to make an informed decision about treatment approach. Citation Format: K. C. Hewitt, C. Yau, R. Mukhtar, C. Thompson, J. Hui, K. Westbrook, J. Jackson, C. Carruthers, C. Farley, S. Bommakanti, K. Brownson, B. Fan, I. Meszoely, T. Balija, M. H. Mcnatt, P. Gilman, J. Marti, T. Li, S. Horton, A. Borowsky, J. Rosenbluth, L. Esserman. Initial results from RECAST DCIS: Multicenter platform trial testing active surveillance and novel endocrine therapy agents for DCIS management [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-03-08.