Abstract Background: Lymphedema is one of the most common and disabling complications of breast cancer treatment. It develops due to impaired lymphatic drainage following surgery and/or radiotherapy, affects up to 15–30% of patients, and significantly reduces quality of life. Current strategies for lymphedema prevention include: • Sentinel lymph node biopsy: minimizes the extent of lymph node removal in the absence of metastatic involvement. • LYMPHA protocol (Lymphatic Microsurgical Preventive Healing Approach): preventive lymphovenous anastomosis (LVA) during mastectomy or axillary lymph node dissection. Both approaches aim to preserve or restore lymphatic pathways, which has been shown to reduce the risk of lymphedema. A critical step in the LYMPHA protocol is accurate visualization of lymphatic vessels, achieved through various dyes. Objective: To evaluate the effectiveness of different dyes in reverse lymphatic mapping. Materials and Methods: This study assessed the ability of different dyes to visualize lymphatic vessels originating from: • the upper limb; • the breast. Dyes used: 1. Indigo carmine (methylene blue) 2. Fluorescein (fluorescein sodium) 3. Indocyanine green Protocol: • One dye was administered for mapping lymphatic pathways from the upper limb, another from the breast. • When combined with SLNB, a radiopharmaceutical was always used alongside one of the dyes. • If axillary lymph node dissection was required, lymphatic mapping of the upper limb was performed using a different dye. Study volume: A total of 86 surgical procedures were analyzed, including: • 9 (10.08%) — indigo carmine only • 14 (15.68%) — fluorescein only • 20 (22.4%) — indocyanine only • 8 (8.96%) — indigo carmine + fluorescein • 14 (15.68%) — indigo carmine + indocyanine • 21 (23.52%) — fluorescein + indocyanine Results: Stable staining of lymphatic pathways from the breast, upper limb, and axillary lymph nodes was achieved in all cases. • At the initial stage, 4 patients receiving indigo carmine had insufficient staining; this was corrected by an additional injection of 5 ml saline. • Indocyanine green demonstrated the highest versatility, enabling transcutaneous visualization of vessels and offering advantages in complex anatomical conditions. • Fluorescein proved practical when expensive equipment was unavailable but was limited in visualization depth. • Indigo carmine was reliable, though limited in depth penetration and occasionally resulted in prolonged skin staining. No adverse events were reported. Discussion and Analysis: • The findings are consistent with international studies (Yamamoto et al., 2020; Boccardo et al., 2016), confirming the high efficacy of ICG in reverse lymphatic mapping. • Use of dye combinations enhances accuracy in identifying relevant lymphatic pathways and reduces the risk of damaging vessels draining the arm. • In resource-limited settings, methylene blue or fluorescein remain optimal choices, whereas ICG provides advantages when appropriate equipment is available. Conclusions: 1. All dyes tested were effective for reverse lymphatic mapping, providing stable staining of lymphatic pathways. 2. Each dye has unique strengths and limitations, necessitating individualized selection based on clinical context and institutional resources. 3. Availability of multiple dyes within the surgical team’s toolkit allows for flexible adaptation of strategy, improving both safety and surgical outcomes. Citation Format: T. G. Mchedlidze, V. V. Vorotnikov, I. V. Kopytych, S. A. Abdugafforov, A. V. Soinov, M. I. Mukueva, M. v. Sharavina. Comparison of dyes for reverse lymphatic mapping in breast cancer surgery 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 PS5-04-24.
Mchedlidze et al. (Tue,) studied this question.