Abstract Background: Accurate targeting of axillary lymph nodes (ALNs) is important in breast cancer surgery, especially in patients with ALNs metastasis. Conventional methods such as charcoal tattooing, needle localization, clips or skin marking with ultrasound have significant limitations: incorrect targeting, rapid dispersion, irreversible pigmentation, or dislocation, complicating precise localization. LuminoMark, a novel near-infrared fluorescence (NIRF) imaging agent combining indocyanine green (ICG) with a dispersion-limiting polymer, offers real-time visualization of ALNs without staining or dislocation risk. Methods: This multicenter, prospective study aims to evaluate the safety and efficacy of LuminoMark compared to standard ALN-targeting methods (charcoal tattooing, needle localization, and ultrasound-guided skin marking). The study includes 330 breast cancer patients (165 per group), including those undergoing upfront surgery or surgery following neoadjuvant chemotherapy. The experimental group receives a 0.2-mL subcutaneous injection of LuminoMark into pathologically confirmed metastatic ALNs prior to surgery, while the control group follows institutional standard targeting procedures. The primary outcome is the successful detection rate of the targeted lymph node and check-up of adverse events, and secondary outcomes include time from incision to node detection, total axillary surgical time, postoperative complications, and correlation with sentinel lymph nodes. A prior Phase 2 trial showed no adverse drug reactions or significant differences in efficacy between doses of LuminoMark® and charcoal. A preliminary study involving 13 patients demonstrated a 100% detection rate with LuminoMark® compared to 92.3% with charcoal, with superior intraoperative visualization and no adverse events. The inclusion criteria include women aged 20-70 with invasive breast cancer and clinically/pathologically confirmed ALN metastasis. Exclusion criteria include stage IV disease, pregnancy, history of allergic reactions to the study drug, or inability to comply with study protocols. All participants undergo postoperative monitoring for 48 hours for safety evaluation. Randomization will be performed preoperatively in upfront surgery cases, or after neoadjuvant chemotherapy in neoadjuvant treatment cases. All procedures adhere to NCCN guidelines, which recommend excision of targeted ALNs. In a real comparative study, if LuminoMark® (100% detection rate) is set as experimental group and the various conventional methods (approximately 89.7%) is set as control group, approximately 1,480 subjects are required for each group. However, this study is composed as pilot study including only 10% of the actual required sample size, and the dropout rate was set to 10%. Therefore, 165 patients (164.4 patients) are needed in each group. Since the control group is composed of methods currently being implemented in each institution (charcoal dyeing, needle positioning, ultrasound-guided skin marking, etc.), the number of patients for each method is expected to be different. However, to configure the ratio as close to 1:1:1 as possible, the number of cases will be assigned differently for each institution. This study seeks to confirm its utility in a clinical setting and support future large-scale trials to establish LuminoMark as a feasible material in targeting ALNs for breast cancer surgery. The full protocol of this study was registered in clinicaltrial.gov (NCT06903429). Citation Format: J. Lee, H. Park, B. Kang, J. Moon, Y. Chae, L. Soo Jung, L. In Hee, J. Park, N. Park, E. Kim, S. Jeong, J. Kang, J. Yang, Y. Lim, T. Jung. A prospective, multicenter comparative pilot study to evaluate targeting axillary lymph node surgery for patients with clinically node-positive breast cancer (LUCAS study, KBCSG36) 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 PS5-08-06.
Lee et al. (2026) studied this question.