Abstract BACKGROUND: Triple negative breast cancer (TNBC) represents 15-20% of all newly diagnosed breast cancers. This form of the disease, which tends to have a higher mutational burden, responds favorably to modern systemic immunotherapy. As a systemic treatment, immunotherapy is associated with rare but potentially life-threatening side-effects. For local, early-stage disease there may be an opportunity to employ targeted intralesional immunotherapy. Preliminary data suggests that intralesional injection of interleukin 2 (IL-2) may be able to produce a favorable pathologic response in TNBC. However, there are currently no protocols for the study of intralesional IL-2 in early-stage TNBC breast cancer. METHODS: This is a single-center, single-arm, non-randomized experimental trial with an initial target enrollment of 10 patients. Women 18-80 years of age with a 2 cm TNBC confirmed on diagnostic imaging and core biopsy are eligible. Patients with major organ dysfunction, history of immune related disease or immunomodulating medication are excluded. In the window-of-opportunity between initial consultation and definitive surgery (6 weeks), eligible women receive weekly (x4), image-guided (ultrasound), intralesional injections of IL-2. Dose calculation per injection is 500,000 IU (5 million IU/ml) per millimetre of tumor width at index diagnostic imaging to a maximum dose of 15 million IU per injection. The primary outcome is pathologic response as defined by the residual cancer burden (RCB) score on final pathology. Secondary outcomes include, protocol feasibility and adverse events (Common Terminology Criteria for Adverse Events). Final pathological specimens will be evaluated for tumor infiltrating lymphocytes (TILs) and PD-L1 expression, in addition to RCB score. EXPECTED OUTCOME: We expect four weekly injections of intralesional IL-2, at a dose of 500,000 IU per mm of maximum tumor width, to be safe and well tolerated in this cohort of patients. Moreover, we anticipate this protocol will demonstrate treatment response characterized by tumor cell death and increased TILs. FUTURE DIRECTIONS: This study will generate preliminary data necessary to support a larger, adequately powered phase II trial to explore treatment optimization and efficacy. Future studies may explore other forms of intralesional immunotherapy, such as PD-L1 inhibitors, and mechanisms to enhance treatment response. Citation Format: R. Hemsworth, G. Knapp, A. Mayo, H. Stewart, A. Goyal, G. Bethune, K. Greenlaw, Z. Kellow, L. Helyer, A. Drohan. Intralesional Injection of IL-2 Prior to Surgery in Early-Stage Triple Negative Breast Cancer 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 PS4-10-25.
Hemsworth et al. (2026) studied this question.