Elsevier

The Lancet Oncology

Volume 14, Issue 6, May 2013, Pages 500-515
The Lancet Oncology

Articles
Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis

https://doi.org/10.1016/S1470-2045(13)70076-7Get rights and content

Summary

Background

The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors.

Methods

We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between Jan 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings.

Findings

72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6% (95% CI 13·6–20·2). Our estimate was 21·4% (14·9–29·8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18·9%, 14·2–24·7), was highest when assessed by more than one diagnostic method (nine studies; 28·2%, 11·8–53·5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19·9%, 13·5–28·2) than it was in those who had sentinel-node biopsy (18 studies; 5·6%, 6·1–7·9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese.

Interpretation

Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder.

Funding

The National Breast Cancer Foundation, Australia.

Introduction

Lymphoedema after breast cancer is characterised by regional swelling, typically in one or both arms, due to excess accumulation of protein-rich fluid in body tissues.1 The adverse consequences of lymphoedema are well known, and cause much morbidity. Arm lymphoedema, and its associated symptoms, such as pain, heaviness, tightness, and decreased range of motion, impede daily function and adversely affect gross and fine motor skills, with negative ramifications for work, home, and personal care functions, as well as recreational and social relationships.2 The appearance of a swollen and sometimes disfigured limb provides an ever-present reminder of breast cancer, which can contribute to anxiety, depression, and emotional distress in affected women.3 Furthermore, preliminary findings show that lymphoedema might also lead to shortened survival.4 In view of the increasing incidence of breast cancer worldwide, understanding the incidence of subsequent secondary lymphoedema and its associated risk factors is clearly of public health importance.

Individual studies report arm lymphoedema in up to 94% of patients with breast cancer,5 with the wide variation (as low as 0%) in reported results an indication of differences in study design, diagnostic methods and criteria used, and timing of lymphoedema measurement with respect to breast cancer diagnosis and treatment.6 Some estimates suggest that about 20% of women will develop arm lymphoedema after breast cancer—this estimation is the average incidence of studies that have been included in several systematic reviews of lymphoedema after breast cancer.7, 8, 9 However, the average incidence of a group of studies does not take into account factors that are known to affect detection rates, such as study design or timing and method of lymphoedema assessment. How common such lymphoedema is after breast cancer is, therefore, unclear. Furthermore, our understanding of acquired and pre-existing risk factors is imperfect. Although more extensive treatment and a higher body-mass index have long been thought to be the major risk factors for the development of lymphoedema, advances in treatment over the past 10–15 years raise questions about whether associations between the risk of lymphoedema and these characteristics, as well as other personal, treatment, and behavioural characteristics, have changed.

The body of evidence relating to the incidence of arm lymphoedema after breast cancer has grown substantially and has improved in quality during the past decade, now including findings from several prospective cohort studies. We therefore did this systematic review and meta-analysis to provide the most up-to-date estimate of the incidence of arm lymphoedema after breast cancer. Also, although the strength of treatment-related risk factors has been assessed in a 2009 meta-analysis,10 it is important to also consider the strength and consistency of the association between lymphoedema and other non-treatment-related risk factors, as well as timely to update findings regarding treatment-related risk factors.

Section snippets

Search strategy and selection criteria

We did a systematic review to identify all studies addressing the incidence of, prevalence of, or risk factors for breast-cancer-related arm lymphoedema. We did a comprehensive search of databases including Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline to identify studies published between Jan 1, 2000, and June 30, 2012, that included women who had undergone surgery for breast cancer. The

Results

We identified 398 potentially relevant citations, of which 79 were included in our analysis (figure 1).

Most studies were either prospective or cross-sectional, but we also identified randomised control trials and retrospective cohort studies, nearly half of studies were from North America, and the most common method of lymphoedema measurement was arm circumference; timing of measurements varied greatly, ranging from 3 months to 20 years after diagnosis (Table 1, Table 2).

Discussion

Our findings suggest that of the 1·38 million women worldwide diagnosed with breast cancer every year,103 295 320 (21%) will develop arm lymphoedema. These findings are based on data from prospective cohort studies, which are well suited for assessing incidence. Although similar to reports from previous reviews,2, 7, 104 which averaged the incidence results from included studies, the subgroup analyses reported here provide additional insight. First, the incidence of arm lymphoedema seems to

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