Topical Tacrolimus in Breast Cancer Lymphedema Prevention: Insights from a Pilot Study

In an open-label, nonrandomized pilot trial of 61 women, topical tacrolimus was evaluated as a preventive topical immunomodulator for breast cancer-related arm lymphedema after axillary lymph node dissection. Applied daily for 12 months, the intervention generated exploratory signals, including smaller mean arm-volume increases and improved patient-reported trajectories.

At the preplanned 12-month assessment (evaluable n = 18 intervention, n = 37 control), lymphedema defined as ≥10% arm-volume increase occurred in 16.7% of the tacrolimus group versus 10.8% of controls (3/18 vs 4/37). The difference did not reach statistical significance (p > 0.05). The reduced evaluable sample reflected loss to follow-up and missing 12-month volume measurements.

Arm-volume change was measured by water displacement volumetry. Mean 12-month increases were 80.7 mL for tacrolimus versus 116.1 mL for controls. Between-group differences favored a smaller volume rise in the intervention arm but did not achieve statistical significance; secondary objective measures therefore suggest a trend toward reduced fluid accumulation without firm evidence of efficacy.

Tolerability was acceptable: adverse events were mostly local and mild (pruritus, transient folliculitis, skin irritation, and occasional flushing related to alcohol content), with a single temporary treatment pause and no unexpected systemic toxicity over 12 months. No serious safety signals emerged in the studied cohort, indicating outpatient application is feasible when clinics monitor for local skin reactions.

Quality-of-life measures returned to baseline only in the tacrolimus group, with slower symptomatic recovery compared with controls—a patient-centered signal that objective incidence metrics did not capture. These PROM trends support emphasizing patient-reported endpoints in future trial designs to capture clinically meaningful benefits.