Loco-regional therapy and the risk of breast cancer-related lymphedema: a systematic review and meta-analysis

Background: This meta-analysis was designed to assess the association between two loco-regional therapies, regional nodal irradiation (RNI) and axillary lymph node dissection (ALND), and breast cancer-related lymphoedema (BCRL).

Methods: We searched PubMed, Science Direct, Embase, and BMJ databases for clinical studies published between January 1, 2010 and January 1, 2020, which assessed risk factors and incidence/prevalence of BCRL. Two investigators independently selected articles to extract relative data and calculate corresponding exact binomial 95% confidence intervals (CIs). In total, 93 articles were reviewed, from which 19 studies were selected. The extracted data were pooled using a random-effects mixed model.

Results: The incidence of lymphedema in the selected studies ranged from 3% to 36.7%, with a pooled incidence of 14.29% (95% CI 13.79-14.79). The summary odds ratio/risk ratio (OR/RR) of ALND vs. no-ALND was 3.67 (95% CI 2.25-5.98) with a heterogeneity (I²) of 81% (P < 0.00001). After excluding the studies with an abnormally high risk of lymphedema from self-reporting, the summary hazard ratio (HR) was 2.99 (95% CI 2.44-3.66) with no heterogeneity (I² = 0%, P = 0.83). The summary OR/RR of patients with vs. without radiotherapy (RT) was 1.82 (95% CI 0.92-3.59), but the RR of RT to breast/chest vs. both axillary and supraclavicular areas was 2.66 (95% CI 0.73-9.70).

Conclusion: Regional nodal irradiation has a significantly higher risk for developing lymphedema than irradiation of the breast/chest wall. Axillary dissection and axillary RT have a similar risk for early-onset of breast cancer-related lymphoedema, although the risk trends higher for axillary dissection.