From Gamma Rays to Green Light: Comparative Efficacy of Indocyanine Green and Technetium-99m in Sentinel Lymph Node Biopsy for Breast Cancer

<b>Background/Objectives</b>: Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in breast cancer. Conventional techniques are radioisotope-based (Technetium-99m, Tc99m) and remain widely used, but novel tracers like Indocyanine Green (ICG) fluorescence provide potential advantages regarding feasibility and logistics. <b>Methods</b>: We conducted a prospective, observational study including 476 female patients diagnosed with primary invasive breast cancer who underwent SLNB at the Institute of Oncology "Prof. Dr. I. Chiricuță", Cluj-Napoca, Romania, between January 2022 and May 2025. Clinical, surgical, and pathological variables were systematically extracted. SLNB was performed using either Tc99m or ICG, according to institutional protocols. Comparative analyses were performed to evaluate sentinel node characteristics, histopathological parameters, and positive surgical margins predictors. <b>Results</b>: The median age was 60 years (IQR: 52-69). Breast-conserving surgery (BCS) was performed in 77.9% of cases, while mastectomy was performed in 22.1%. Sentinel lymph node positivity was reported in 25.6% of cases, with no significant differences in the number of excised or metastatic nodes between Tc99m and ICG (mean nodes: 3.23 vs. 3.20, <i>p</i> = 0.860; mean positive nodes: 0.35 vs. 0.36, <i>p</i> = 0.897). Histologically, invasive carcinoma NST was predominant (90.1%), and surgical margins were negative in 96.8% of patients, with all margin-positive cases occurring following BCS. No pathological markers (grade, Ki67, TILs, DCIS extent) predicted margin status or nodal involvement. Notably, younger age correlated inversely with the extent of ductal carcinoma in situ (r = -0.21, <i>p</i> < 0.00001). <b>Conclusions</b>: Tc99m and ICG provided comparable diagnostic performance in performing SLNB, with equivalent rates of nodal detection and pathological yield. These findings support that ICG is a safe and effective alternative for routine axillary staging in breast cancer.