Risk factors of unilateral breast cancer-related lymphedema: an updated systematic review and meta-analysis of 84 cohort studies

Purpose: To review and update the incidence and risk factors for breast cancer-related lymphedema based on cohort studies.

Methods: The study was guided by the Joanna Briggs Institute methodology and the Cochrane handbook for systematic reviews. PubMed, EMBASE, CINAHL, Scopus, Web of Science, The Cochrane Library, CNKI, SinoMed, and Wan Fang Database were searched from inception to November 15, 2021. Cohort studies reported adjusted risk factors were selected. PRISMA guideline was followed. Study quality were evaluated using the Newcastle-Ottawa scale. Random-effects models were adopted. The robustness of pooled estimates was validated by meta-regression and subgroup analysis. Lymphedema incidence and adjusted risk factors in the multivariable analyses with hazard / odds ratios and 95% CIs were recorded.

Results: Eighty-four cohort studies involving 58,358 breast cancer patients were included. The pooled incidence of lymphedema was 21.9% (95% CI, 19.8-24.0%). Fourteen factors were identified including ethnicity (black vs. white), higher body mass index, higher weight increase, hypertension, higher cancer stage (III vs. I-II), larger tumor size, mastectomy (vs. breast conservation surgery), axillary lymph nodes dissection, more lymph nodes dissected, higher level of lymph nodes dissection, chemotherapy, radiotherapy, surgery complications, and higher relative volume increase postoperatively. Additionally, breast reconstruction surgery, and adequate finance were found to play a protective role. However, other variables such as age, number of positive lymph nodes, and exercise were not correlated with risk of lymphedema.

Conclusion: Treatment-related factors still leading the development of breast cancer-related lymphedema. Other factors such as postoperative weight increase and finance status also play a part. Our findings suggest the need to shift the focus from treatment-related factors to modifiable psycho-social-behavioral factors.