Targeting Lymphedema in Overweight Breast Cancer Survivors: A Pilot Randomized Controlled Trial of Diet and Exercise Intervention.

Background/Objectives: Breast cancer-related lymphedema (BCRL) is more prevalent and severe in women with overweight or obesity. This study evaluated the effect of a comprehensive lifestyle intervention-comprising supervised exercise, a hypocaloric Mediterranean diet, and optional meal replacement-on lymphedema outcomes in this population. Methods: In this pilot randomized controlled trial, 112 women with BCRL and BMI 25-40 kg/m2 were assigned to an intervention group-receiving supervised resistance and aerobic training, dietary counseling, and optional high-protein meal replacement-or to a control group with standard advice. The primary outcome was change in affected limb volume at 3 and 6 months. Secondary outcomes included morphofunctional parameters, muscle strength, dietary intake, and serum levels of cytokines (IL-1β, IL-6, IL-10, and TNF-α). Analyses also explored outcomes according to whether participants achieved ≥ 5% weight loss. Results: Ninety-four participants completed the trial (intervention n = 43, control n = 51). At 6 months, women who achieved ≥5% weight loss had greater reductions in affected limb volume (-664.9 ± 362.1 mL vs. -395.6 ± 596.9 mL). The intervention group showed significantly greater improvements in BMI (-1.14 ± 1.22 kg/m2), waist circumference (-3.59 ± 4.6 cm), triceps skinfold (-4.61 ± 3.02 mm), fat mass (-2.38 ± 2.75 kg), extracellular water (-0.58 ± 0.85 L), and quadriceps strength (+7.1 ± 9.7 kg). No significant changes were observed in circulating cytokines. Conclusions: In this pilot randomized controlled trial, a structured dietary and exercise intervention improved morphofunctional outcomes in overweight women with BCRL. Weight loss of ≥5% emerged as a potentially relevant therapeutic target that may inform the design of future studies aimed at optimizing lymphedema management.