Assessment and experimental treatment of breast cancer-related lymphedema with adipose-derived regenerative cells and lipotransfer

Breast cancer-related lymphedema (BCRL) can be a devastating late-effect to breast cancer treatment. The disorder is associated with lymphatic fluid stasis in the subcutaneous tissue and swelling due to fluid and fat accumulation. Most treatments aim to improve BCRL patients’ quality of life and reduce the volume of BCRL. Cell therapy using adipose-derived regenerative cells (ADRCs) has shown promising results for lymphedema treatment in preclinical studies and earlyphase clinical studies, however high-level evidence is lacking and there is an information gap in subjective patient-reported and objective outcome measures in BCRL.


This PhD thesis cover results from four clinical studies using observational and experimental research methodologies. The main purpose of this thesis was to investigate the clinical efficacy of ADRC therapy in treating BCRL and secondarily to examine BCRL symptomology and biocomposition.


Study 1: This was a phase-1 clinical study evaluating ADRC and lipotransfer in the treatment of BCRL with four years of follow-up (n= 10). The results showed that several patient-reported outcome measures improved after treatment. However, we did not find treatment to decrease objective lymphedema severity in this study, consistent with prior results up to one year.


Study 2: This was a descriptive cross-sectional study investigating the impact of BCRL on HRQoL (n= 1067). We found that breast cancer patients with BCRL had a significant impaired HRQoL compared to breast cancer patients without BCRL. Within the BCRL population, we surprisingly found that BMI, disease severity, hand, and dominant arm affection only had a minor impact on HRQoL.


Study 3: This was a descriptive cross-sectional study investigating the impact of cellulitis on BCRL biocomposition (n= 206). We found that BCRL patients with cellulitis had more severe objective lymphedema with more excess fat and lean mass in the BCRL arm. In addition, patients BMI, body fat mass, and arm dominance were also associated with excess fat and lean mass in BCRL.


Study 4: This was a randomized controlled trial evaluating the clinical efficacy of ADRC and lipotransfer for alleviating BCRL (n= 80). The results showed equivalent outcomes for the treatment and placebo groups. In fact, both the treatment and placebo groups experienced some subjective improvements, but no decrease in objective lymphedema severity was observed in either group.