The detection of sedentary lifestyle as a risk factor is, to our knowledge, a new finding and could

be as a consequence of a major lymph flow mechanism (the muscle pump) being inactive.
There are several factors to be considered before our risk-factor findings are used for risk-
stratification purposes. First, these risk factors alone do not accurately predict who will develop
arm lymphoedema and who will not. These specific factors represent six of 12 identified risk
factors in one, prospective, population-based cohort study, which together explained only 35% of
variation between those who did and those who did not develop lymphoedema.39 Furthermore,
women can and do present with arm lymphoedema despite having healthy bodyweight, regular
physical activity levels, and lumpectomy surgery. Finally, little is known about the potential
contribution of the cancer itself, or the possible importance of genetic predisposition, to
lymphoedema risk. Findings from animal models110 and one study in human beings111 provide
preliminary evidence for a contribution of genetic susceptibility to the development of secondary
lympho edema after breast cancer. Nonetheless, current understanding of risk factors can inform
lymphoedema prevention and management strategies. Although treatment-related risk factors are
largely not modifiable (because they are generally dictated by the type and stage of disease and
available treatment options), substantial scope exists for the modification of patients' physical
activity levels and bodyweight after breast cancer: most women with breast cancer are
insufficiently active at diagnosis112114 and more than 50% are overweight or obese.115
Further research is needed to improve our understanding of risk factors (including further
exploration of known risk factors, such as whether lymphedoema rates differ between those with
delayed axillary-lymph-node dissection after sentinel-node biopsy compared with axillary-
lymph-node dissection from the outset), as well as prevention and treatment strategies. Only with
. increased knowledge will we be in a position to improve further the lives of women with breast
cancer, and reduce the overall socioeconomic burden of this disabling, distressing disorder.

398 individual studies identified and screened

286 excluded after assessment of abstracts and titles
112 full-text articles for eligibility
33 articles excluded
7 duplicate or secondary analyses
3 recorded pre-operation incidence only
19 did not meet eligibility criteria
3 simply assessed lymphedema
1 was done more than 30 years ago
79 articles included in review (74 incidence
and 31 risk factors)
72 studies on incidence*
29 studies on risk factors
Figure 1: Flow diagram of study selection for inclusion in this review and meta-analysis *We
included 74 articles, which presented results of 72 studies (two studies were each presented in
two articles). We included 31 articles, which presented results of 29 studies (two studies were
each presented in two articles).

Included studies (n)

Incidence (%; 95% CI)
Pooled estimate
All studies 72 166 (136202)
Prospective cohort studies 30 214 (149298)
Randomized clinical trial 7 104 (79135)
Retrospective cohort 10 84 (54128)
Cross-sectional studies 25 177 (138224)
Location of study
Asia 4 180 (102298)
Australasia 7 215 (150298)
Europe 17 142 (109184)
Middle East 1 175 (139218)
North America 32 210 (151285)
South America 3 137 (81222)
UK 8 84 (51136)
Axillary surgery
SLNB 18 56 (6179)
ALND 18 199 (135282)
Measurement method*
Lymphoscintigraphy 1 50 (16144)
Bioelectrical impedance 3 159 (46426)
Self-reported clinical diagnosis 5 125 (62236)
Clinical diagnosis 7 126 (81193)
Circumference 38 148 (114190)
Perometry 17 164 (109241)
Self-reported swelling 19 204 (138290)
More than one measure 9 282 (118535)
Time since breast cancer diagnosis or surgery*
3 to <6 months 8 103 (62167)
6 to <12 months 15 138 (73245)
12 to <24 months 24 189 (142247)
2 to <5 years 30 186 (136248)
5 years 16 156 (100235)
More than one time category 6 76 (27195)
ALND=axillary-lymph-node dissection. SLNB=sentinel-lymph-node biopsy. *Numbers
(percentages) might not add to 72 (100%) because some studies measured lymphoedema with
more than one method or at more than one timepoint.
Table 1: Incidence of breast cancer-related lymphoedema

Contributors TD, BN, and SH participated in the conception and design of the review. TD and
SR participated in the extraction and analysis of data. TD, SR, BN, and SH participated in the
interpretation of data and writing of the paper. All authors approved the final version.