A systematic review and meta-analysis of the incidence of breast cancer-related lymphoedema due to treatment combinations

BACKGROUND Breast cancer related-lymphoedema (BCRL) is a chronic, debilitating disease for which there is no cure. A meta-analysis was conducted to estimate the association between different treatment combinations on the incidence of BCRL.

The review was conducted according to PRISMA guidelines with four databases searched for studies published from 2000-2020, including OVID Medline, OVID Embase, Cochrane Library for Registered Controlled Trials, and Cumulative Index to Nursing and Allied Health, yielding 2640 studies. A random effects model was used to determine BCRL incidence rates stratified by treatment types of the qualifying studies.

The pooled incidence rate was 23% (95% CI 20.8 – 25.4) for patients who received axillary lymph node dissection (ALND) and 5.6% (95% CI 4.5 – 6.8) for patients who underwent sentinel lymph node biopsy (SLNB). A higher level of intervention to the axilla was identified as the key factor associated with significantly increased BCRL incidence, including ALND (p<0.001), the number of lymph nodes removed (p<0.001), and axillary radiotherapy (p<0.001). Higher patient BMI was also identified to increase BCRL incidence. Combinations of other treatments, in conjunction with ALND or SLNB, did not lead to statistically significant differences in incidence. Furthermore, different diagnostic criteria resulted in substantial variation in BCRL incidence rates.

Axilla intervention was associated with increased BCRL incidence including ALND, number of lymph nodes removed, and radiotherapy. The inclusion of additional surgical or non-surgical treatments did not. This analysis re-emphasises the clear need for standardised reporting of patient treatments as well as universally applied diagnostic protocols. Competing Interest Statement The authors have declared no competing interest. Funding Statement This project is funded by the National Institute for Health and Care Research (NIHR) under its Invention for Innovation Programme (Grant Reference Number NIHR201646). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes Funding: This project is funded by the National Institute for Health and Care Research (NIHR) under its Invention for Innovation Programme (Grant Reference Number NIHR201646). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. Conflicts of Interest: Dr. Paul Thiruchelvam has received honoraria from Stryker, Endomagnetics for lectures and is a consultant for Cytoveris. The other authors have no relevant conflicts to report. Data Availability: Data is available upon reasonable request. Data Availability All data produced in the present study are available upon reasonable request to the authors