Early Disturbance of Lymphatic Transport as a Risk Factor for the Development of Breast-Cancer-Related Lymphedema

SIMPLE SUMMARY: Lymphedema is a chronic debilitating condition that requires continuous attention. ICG fluoroscopy shows a detailed superficial lymphatic architecture, can provide additional information regarding the functionality of lymphatic transport and can show early abnormalities of the lymphatic system. The aim of this study is to investigate whether his early disturbance of lymphatic transport visualized by lymphofluoroscopy is a risk factor for the development of breast-cancer-related lymphedema (BCRL). No such research has been conducted to date. All patients scheduled for breast cancer surgery with unilateral axillary lymph node dissection or sentinel node biopsy were considered. Patients were assessed at baseline and 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. During each visit, a clinical assessment was performed to determine the presence of clinical lymphedema (≥5% increase in relative arm volume difference compared to the baseline value). Variables related to (1) the disturbance of lymphatic transport, (2) the demographics and general health of the patient and (3) the breast cancer and treatment of the patient were also investigated. Early disturbance of lymphatic transport visualized by lymphofluoroscopy was identified as a risk factor for the development of clinical BCRL. Age and axillary lymph node dissection were withheld as independent risk factors. A surveillance program of these high-risk patients with lymphofluoroscopy can be useful to identify lymphedema in a subclinical stage and prevent development to more advanced stages. ABSTRACT: Introduction: Breast-cancer-related lymphedema (BCRL) is a frequently occurring and debilitating condition. When lymphedema is diagnosed late, treatment can be expected to be less effective. Lymphofluoroscopy can provide details about the superficial lymphatic architecture and can detect an early disturbance of lymphatic transport (i.e., dermal backflow) before the lymphedema is clinically visible. The main objective of this study is to investigate whether this early disturbance of lymphatic transport visualized by lymphofluoroscopy is a risk factor for the development of BCRL. Methodology: All patients scheduled for unilateral breast cancer surgery with axillary lymph node dissection or sentinel node biopsy were considered. Patients were assessed at baseline and 1, 3, 6, 9, 12, 18, 24 and 36 months postoperatively. During each visit, a clinical assessment was performed to determine the volume difference between both arms and hands (through circumference measurements and water displacement). Clinical BCRL was defined as a ≥5% increase in relative arm volume difference compared to the baseline value. Variables related to (1) the disturbance of lymphatic transport (through lymphofluoroscopy), (2) the demographics and general health of the patient and (3) the breast cancer and treatment of the patient were collected. Results: We included data of 118 patients in the present study. Thirty-eight patients (39.8%) developed BCRL. Early disturbance of lymphatic transport was identified as a risk factor for the development of clinical BCRL (HR 2.808). Breast-cancer- and treatment-related variables such as axillary lymph node dissection (ALND) (HR 15.127), tumor stage (HR 1.745), mastectomy (HR 0.186), number of positive lymph nodes (HR 1.121), number of removed lymph nodes (HR 1.055), radiotherapy of the axilla (HR 2.715), adjuvant taxanes (HR 3.220) and postsurgical complications (HR 2.590) were identified as significant risk factors for the development of BCRL. In the multivariate analysis, age and ALND were withheld as independent risk factors for the development of BCRL. Conclusion: Lymphofluoroscopy can identify an early disturbance of lymphatic transport after breast cancer treatment. Patients with an early disturbance of lymphatic transport are considered to be a high-risk group for the development of BCRL. This study also confirms that age and ALND are predictors for the development of BCRL. Therefore, a surveillance program of these patients with lymphofluoroscopy could be useful to identify lymphedema in subclinical stages.