The Prevalence of Lymphedema and Changes in Practice by hedongchenchen


									                                                                                                                  Page 1

The Prevalence of Lymphedema and Changes
in Practice to
Reduce its Occurrence in Women with Breast
Sarah A McLaughlin and Kimberly J Van Zee
Affiliation: Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Evelyn H Lauder Breast
Center, New York, NY, USA
Lymphedema is a chronic debilitating condition affecting many long-term breast cancer survivors. The incidence of
lymphedema is
reported to range from 6% to 70% after axillary surgery for breast cancer; however, its true incidence has been difficult to
quantify because of
the lack of standard diagnostic and universal assessment criteria. Extent of nodal dissection, axillary radiation, injury, and
infection in the
ipsilateral upper extremity remain significant risk factors for the development of lymphedema. Current changes in
axillary management,
including the adoption of sentinel node biopsy, the selective omission of completion axillary dissection after a positive
sentinel node, and the
elimination of axillary staging, have been proposed to further reduce axillary morbidity. Early research on lymphedema
risk reduction focuses
on supervised weight training after axillary surgery, axillary reverse mapping to avoid removal of lymph nodes draining
the upper extremity,
and incorporation of fused single photon emission computed tomography (SPECT)-CT axillary nodal images to better
plan adjuvant radiation
Keywords: lymphedema, axillary dissection, sentinel node biopsy, breast cancer, survivorship, patient perceptions
Correspondence: Kimberly J Van Zee, Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center,
and Weill Medical
College of Cornell University, Evelyn H Lauder Breast Center, 300 E. 66th St., New York, NY, 10065, USA. Tel:
(1)-646-888-5362; Fax: (1)-646-
888-4920; e-mail:
According to the National Cancer Institute and the
Surveillance Epidemiology and End Results (SEER) database,
the mortality rate for breast cancer has been in significant
decline [1, 2], resulting in more than 2.5 million breast cancer
survivors. Today, issues of survivorship are the focus of much
research in an effort to improve the overall quality of life in
these women. Lymphedema remains a focus of survivorship
research as it is a commonly feared and potentially long-term
complication of breast cancer therapy for which no cure exists.
Lymphedema is a chronic, disfiguring, and potentially
disabling accumulation of protein-rich fluid in the interstitial
tissues resulting in edema, hypertrophy, and eventually
fibrosis of the extremity tissues. In breast cancer, the term
lymphedema classically refers to swelling of the upper
extremity and will be the focus of this review; however, it is
recognized that it can be associated with a constellation of
other symptoms including musculoskeletal pain, paresthe-
sias, and loss of shoulder mobility, especially in the most
advanced stages. The physical changes in the upper extremity
due to lymphedema may be difficult to conceal and may
impair one from performing activities of daily living. Owing
to the fear of developing lymphedema, many women alter
their lifestyles, avoiding recreational activities and practicing
risk-reducing behaviors in an effort to keep symptoms from
worsening [3]. Furthermore, despite the lack of supportive
data, the majority of women avoid having blood pressures
obtained, blood draws taken, and intravenous needles placed
in the ipsilateral arm because of the risk of developing
lymphedema [3]. Clearly, lymphedema or the risk of
developing lymphedema remains a constant reminder of a
woman’s lifelong struggle with breast cancer.
The true incidence of lymphedema has been difficult to
determine accurately. The reasons for this are twofold. First,
no standardized definition of what constitutes lymphedema
exists. Both objective and subjective measures have been used.
However, the objective measure used—volume displacement,
truncated cone volumes, or simple circumferential upper
extremity arm measurements—is left to the discretion of the
investigator, who may use varying thresholds for diagnosing
lymphedema. To be meaningful, objective measures must
include baseline pretreatment values and both ipsilateral and
contralateral upper extremity measurements.
Subjective assessments of lymphedema give insight into the
patient’s perception of lymphedema, which may arguably be
the most important definition, but rarely are these subjective
findings correlated with objective measures. The dilemma
remains that measurement changes alone may not capture all
patients suffering from clinically significant lymphedema and
may overdiagnose those who are unaffected by their
measurement change.
Second, lymphedema may have a delayed onset of up to
20 years after breast cancer treatment [4]. Most series report
EJCMO 2010; 2:(2). June 2010

                                                                  Page 2
only short-term follow-up of 1–3 years, thereby potentially
missing those with delayed presentation. Although 75–90%
of women affected with lymphedema present with swelling
within 3 years of treatment, the remaining women affected
with lymphedema will present with swelling at a rate of 1%
per year to 20 years [4, 5]. Therefore, it is likely that
lymphedema is more common than generally reported.
Historical estimates demonstrate wide variations in the
incidence of lymphedema, ranging from 6% to 70% [6–18].
Most attribute this wide range to differences in surgery in
both the breast and the axilla, as well as to variations in
postoperative radiation usage. In the 1990s, Petrek and
Heelan reported the lymphedema rate after axillary lymph
node dissection (ALND) was 6–30% [12], but in a study in
2001 evaluating the presence of lymphedema in 20-year breast
cancer survivors, the incidence of lymphedema was nearly
50% [4]. More recent studies confirm these findings and
underscore the necessity of long-term follow-up for detection
of lymphedema. Using a standardized telephone question-
naire validated against arm measurements, Norman et al [5,
19] conducted a 5-year population-based prospective study of
631 women who were treated for breast cancer between 1999
and 2001. They report a cumulative incidence of lymphedema
of 42%, with 89% of these patients having their first
lymphedema occurrence within 3 years of cancer diagnosis.
The adoption of sentinel lymph node biopsy (SLNB) as
standard of care for axillary staging has significantly reduced
the rate of lymphedema (Table 1). The results of three
prospective randomized trials and several non-randomized
trials conclude that rates of lymphedema after SLNB range
from 0% to 7% [3, 10, 14, 20–29]. However, these trials are
limited by the lack of long-term follow-up as most are
reported between 6 and 36 months post surgery. The largest
prospective series to date with 5 years of follow-up comparing
rates of lymphedema after SLNB and ALND followed nearly
1000 patients. All patients had baseline ipsilateral and
contralateral circumferential arm measurements, and all
patients completed a standardized interview process to
evaluate subjective findings of lymphedema [3, 24]. Overall,
5% of women undergoing SLNB had objective measurements
consistent with lymphedema, compared with 16% of patients
undergoing ALND (P,0.001). Interestingly, however, lym-
phedema was subjectively reported less frequently than it was
measured in women having SLNB, but more frequently than it
was measured in women having ALND, at 3% and 27%,
respectively. Furthermore, only 41% of women reporting arm
swelling had measured lymphedema. This finding suggests
that the most accurate diagnostic criteria for lymphedema
should include correlation of objective and subjective
measures, as reporting only one aspect may incorrectly
estimate the actual incidence of clinically significant lymphe-
Numerous published series have examined the associations
between breast cancer treatment factors and the development
of lymphedema. Unfortunately, the strength of each risk
factor is inconsistent across all series. The most commonly
cited contributing factors are extent of axillary surgery and the
use of axillary radiation.
Although some studies have found no relation between the
number of nodes removed and the incidence of lymphedema
Table 1. Select Series reporting Measured or Patient-Perceived Lymphedema after Sentinel Lymph Node Biopsy

Author, year [ref]


Follow-up (months)

Lymphedema by measurement or

patient perception

Proportion with lymphedema

Sener, 2001 [27]


Median 24



Veronesi, 2003 [28]


Median 24


Golshan, 2003 [20]


Minimum 12



Leidenius, 2005 [10]


Median 36



Ronka, 2005 [14]


Median 12



Purushotham, 2005 [25]


Median 12


OR 0.3

Barranger, 2005 [75]


Mean 20

Patient perception


Mansel, 2006 [23]


Median 12



Wilke, 2006 [29]


Median 6



Langer, 2007 [21]


Median 30

Patient perception


Lucci, 2007 [22]

Median 12



McLaughlin, 2008 [24]


Median 60



McLaughlin, 2008 [3]


Median 60

Patient perception


Ferreira, 2008 [76]


Mean 24



Yen, 2009 [77]


Median 48

Patient perception


OR, odds ratio.

European Journal of Clinical & Medical Oncology
EJCMO 2010; 2:(2). June 2010

                                                               Page 3
after either SLNB or ALND [22], or after ALND alone [30],
others have suggested that the number of nodes removed is
related to the risk of lymphedema. Kiel and Rademacker [31]
found an odds ratio of 13 (95% CI 2–103) for more than 16
nodes removed. Similarly, Herd-Smith et al [32] found a
hazard ratio of 1.6 (95% CI 1–2.7) for patients having more
than 30 nodes removed compared with those having less than
20 removed. Paskett et al [33] found that the risk of arm
swelling increased by 3% with the removal of each
subsequent lymph node. Furthermore, the finding of lower
rates of lymphedema after SLNB compared with ALND
supports the concept that the risk of lymphedema is
proportional to the extent of axillary surgery.
Axillary radiation has also been used as a primary treatment
modality. Although fewer data exist regarding long-term
risks, it is associated with a 2.0- to 4.5-fold increased risk of
lymphedema, in addition to other long-term morbidities,
including brachial plexopathy [34]. The synergistic combina-
tion of ALND and axillary radiation appears to have the
highest morbidity, with a 3.5- to 10.0-fold increased risk for
lymphedema [35–39] when compared with surgery alone.
Current treatment strategies generally avoid direct axillary
radiation unless more than 10 lymph nodes are involved with
metastatic disease. Despite technical advances in radiation
planning, the amount and effect of scattered radiation
tangents to the axilla on lymphedema risk is unclear, but
must be considered as more patients are completing radiation
therapy after breast-conserving surgery and, more recently,
after mastectomy [40].
Other frequently reported risk factors include patient age,
body mass index (BMI), injury or infection in the ipsilateral
arm, and the presence of positive lymph nodes. Although data
both support and refute age as a risk factor for lymphedema
[33, 41, 42], a patient’s age may influence one’s perception of
lymphedema, with younger patients reporting lymphedema
more frequently than older patients [3, 24]. Increased BMI or
weight gain since surgery has been associated with a higher
risk for lymphedema [4, 18, 24, 33, 38]. Infection and injury
are also associated with significant increased risk for
lymphedema, but both are difficult to rigorously evaluate as
each is influenced by recall bias [3, 4, 22, 24, 29].
The most recent meta-analysis on lymphedema risk factors
reviewed 98 studies conducted in the United States and
Canada through January 2008 [43]. The authors report a
significant increased risk of lymphedema for women under-
going mastectomy compared with lumpectomy (RR 1.42; 95%
CI 1.15–1.76), axillary dissection compared with no dissection
(RR 3.47; 95% CI 2.34–5.15), ALND compared with SLNB
(RR 3.07; 95% CI 2.20–4.29), radiation therapy vs no
radiation therapy (RR 1.92; 95% CI 1.61–2.28), and for
positive vs negative axillary lymph nodes (RR 1.54; 95% CI
1.32–1.80). Although this analysis demonstrates the most
comprehensive review of lymphedema risk factors, the
heterogeneity of the data must be recognized, as 11 different
definitions for lymphedema were used and follow-up ranged
between 1 month and 30 years among the 98 studies reviewed.
Data are beginning to accumulate regarding lymphedema
progression, of which little was previously known. At first
occurrence, lymphedema is generally mild, and the data
suggest that it tends to remain mild over time. The authors’
experience is that, at 5 years post surgery, the majority of
women with lymphedema after SLNB or ALND have only mild
swelling (measurement difference of less than 2 cm between
affected and unaffected upper extremities) involving only the
upper arm, not the forearm or hand. Severe lymphedema
(greater than 5 cm difference) was rare and documented in only
3% of women after ALND and 0.5% after SLNB [24]. These
data support previously published documented rates of severe
lymphedema [4]. Contemporary studies find that the majority
of women with lymphedema have only mild lymphedema
(definitions vary) and further suggest that mild lymphedema is
an independent risk factor for the future development of severe
lymphedema. Although this concept is intuitive, little pro-
spective documentation exists to support this theory. Recently,
Norman et al [5] found that, although the majority of patients
had only mild lymphedema, defined subjectively as swelling
noticeable only to themselves, these patients were three times
more likely to develop moderate or severe lymphedema,
defined subjectively as swelling noticeable to close relatives
or others. Additionally, patients reporting symptoms of tight
clothing or jewelry were more likely to develop lymphedema at
a later date (HR 7.37; 95% CI 4.26–12.76). Similarly, Bar Ad et
al [44] found that 48% of patients with mild lymphedema at the
time of first occurrence progressed to more severe lymphe-
dema at 5 years. The influence of treatment interventions is not
recorded in these analyses, but likely slow progression from
mild to severe lymphedema. Nonetheless, the presence of mild
subjective or objective lymphedema should be viewed as a risk
factor for future debilitating lymphedema.
The adoption of SLNB as the standard method of axillary
staging has markedly reduced the incidence of lymphedema. It
is documented to have low short-term rates of axillary
recurrence (0.0–1.4%), even when disease is identified within
the sentinel node [45, 46]. Currently, further efforts to reduce
lymphedema and axillary surgery morbidity focus on reducing
the number of patients undergoing completion ALND after
positive SLNB. Some argue that SLNB is both diagnostic and
therapeutic as 50–80% of patients have no additional positive
non-sentinel lymph nodes at completion ALND, and that it
therefore brings into question the value of completion ALND
[47, 48]. As a result, numerous studies have evaluated tumor
and nodal characteristics associated with additional positive
non-sentinel lymph nodes [47–51], and have prompted the
development and usage of multiple nomograms in clinical
practice to predict the likelihood of positive non-sentinel nodes
[52, 53]. The risk estimated by the nomogram acts as an aid to
the clinician and patient to assess the risk of residual axillary
disease if completion ALND is omitted. It is therefore not
surprising that current trends in axillary surgery evaluated by
Bilimoria et al [54] demonstrate that 45% of patients with
Prevalence and treatment of lymphedema in breast cancer
EJCMO 2010; 2:(2). June 2010

                                                                       Page 4
micrometastatic disease in the sentinel node did not complete
ALND in 2005 compared with only 24% in 1998 (P,0.001). At
5 years of follow-up, the authors found that this trend resulted
in no change in either axillary recurrence or survival rates in this
population. Others have proposed forgoing axillary evaluation
altogether in certain populations. Martelli et al [55] completed a
randomized trial comparing ALND with no ALND in patients
aged 65–80 years with T1N0 estrogen receptor-positive breast
cancer. All patients were given tamoxifen. With 5 years of
follow-up, they concluded that older patients with T1N0 breast
cancer can be treated with breast surgery alone without
adversely affecting breast cancer mortality or overall survival,
arguing that even SLNB can be avoided in these patients.
At least two prospective randomized trials have been
designed comparing observation vs completion ALND for
patients with positive SLNB, including the International
Breast Cancer Study Group 23-01, which is open and
ongoing, and the American College of Surgeons Z-0011 trial,
which closed due to poor accrual. Results from both are
pending. Additionally, the European Organization for
Research and Treatment of Cancer (EORTC) cooperative
group is conducting a phase III trial named the AMAROS trial
(10981) comparing axillary radiation with completion ALND
for patients with positive SLNB. If these trials demonstrate
acceptable outcomes for the groups without completion
ALND, it is likely that the number of patients with a positive
SLNB pursuing completion ALND will continue to decrease,
which in turn will result in an overall lower incidence of
lymphedema. Long-term follow-up (.5 years) of these
populations is imperative to document such a trend.
No standard monitoring exists for the diagnosis of lymphe-
dema after breast cancer treatment. More rigorous lymphedema
monitoring may be of benefit if early intervention strategies are
proven successful. Recent data suggest that patients complain-
ing of arm symptoms such as heaviness, swelling, or tight
jewelry are more likely to develop lymphedema [5, 19]. Data
from a 5-year National Institutes of Health study support the
view that early assessment and intervention may prevent the
progression of lymphedema [56]. The authors used a simple,
portable, cost-effective, and easily interpretable bioimpedance
device to measure changes in arm fluid. It compares the
ipsilateral and contralateral arms, generating a lymphedema
index (L-DexTM) value [56, 57]. The procedure is performed
preoperatively and at 3-month, 6-month, 12-month, and annual
time points. A score increase of more than 10, or one that
registers outside the normal range, prompts intervention. After
4 weeks of compression therapy, patients demonstrated a
significant reduction in mean arm volume of 48 mL (¡103 mL;
P,0.0001) and maintained the reduction for 4.8 (¡4.1) months.
Validation of these findings, ease of adoption into clinical
practice, and longer follow-up are needed.
Once the diagnosis of lymphedema is made, many options
exist for maintenance and treatment of symptoms.
Therapeutic interventions include counseling on skin and
nail care, massage, manual lymphatic drainage, and com-
pression garments, bandages, or devices. Although the
Lymphology Association of North America has standardized
examinations to certify lymphedema therapists, treatment
approaches are not standardized among therapists [58].
Manual lymphatic drainage is a gentle massage technique that
includes lightly stroking the arm to stretch the superficial
lymphatic vessels and promote contraction of the underlying
deep lymphatics. Multiple trials demonstrate extremity
volume reductions of 130–400 mL per arm after 2–4 weeks
of therapy, but acknowledge that effective maintenance
therapy is required to sustain this initial reduction [59–63].
Multilayer compression bandages serve to increase tissue
pressure, promoting lymphatic and venous fluid return to
reshape the extremity. Although effective at reducing limb
volume, proper application of the bandages is difficult for
patients to learn and time-consuming to apply. Compression
sleeves and garments are easier to apply, but their mechanism
of action remains unclear. They are helpful in maintaining
tissue–fluid balance, preventing skin stretching, and protect-
ing skin from trauma. Because of their elasticity, compression
garments are not recommended for overnight use.
In addition to these standard treatment recommendations,
renewed interest exists in the role of exercise for lymphedema
treatment and risk reduction. Ahmed et al [64] randomized 78
women without lymphedema to weight training or standard
care for 6 months after ALND or SLNB and found no evidence
of increased incidence of lymphedema in the intervention
group. Sagen et al [65] found similar results with 2 years of
follow-up. Recently, Schmitz et al [66] completed a rando-
mized controlled trial of supervised twice-weekly progressive
weight lifting in 141 breast cancer survivors with stable
lymphedema. All patients were required to wear a well-fitted
compression garment. They found that 11% of women in the
weight lifting group and 12% of those in the control group
had an increase of more than 5% in arm swelling (cumulative
incidence ratio 1.0; 95% CI 0.88–1.13), and concluded that
slow progressive weight lifting had no significant impact on
arm swelling and actually decreased episodes of lymphedema
exacerbation (P50.04). These findings by Schmitz et al mirror
the findings of others previously demonstrating that exercise
may not exacerbate existing symptoms of lymphedema [61].
Collectively, these four studies suggest that, contrary to prior
teachings, supervised activity and exercise should be encour-
aged in breast cancer survivors.
A new surgical technique, called axillary reverse mapping
(ARM), was introduced in 2007 in an attempt to further
reduce the incidence of lymphedema. ARM is based on the
concept that the arm and breast each have separate primary
drainage pathways. By injecting blue dye into the arm and
radioisotope into the breast, one can distinguish between the
two pathways and spare lymphatics draining the upper
extremity. Successful mapping of the upper extremity path-
way has been demonstrated in 40–90% of cases; however, a
European Journal of Clinical & Medical Oncology
EJCMO 2010; 2:(2). June 2010
                                                                 Page 5
fraction of women have overlapping arm and breast drainage
pathways, making salvage of the upper extremity pathways
difficult [67–71]. No lymphedema is reported in patients
completing the ARM procedure, but follow-up is short at only
6 months [67]. Although promising in concept, clinicians
have been cautious in adopting ARM into clinical practice
because mapping may be altered in women with significant
axillary tumor nodal burden (.four positive nodes) [69].
Overlapping breast and upper extremity drainage patterns are
seen in up to 20% of women [72], and the ARM node has
been involved by breast cancer in 9–18% of patients [72, 73].
Further study of and indications for this technique are
Finally, Cheville et al [74] have explored the possibility of
being able to map lymph nodes draining the upper extremity
using 99mTc-sulfur. Using a dual-head single photon
emission computed tomography (SPECT) camera and low-
dose, single-slice computed tomography (CT) images, they
are able to develop fusion images which serve as a map of
upper extremity lymph node coordinates. Ideally, these nodes
can be avoided in three-dimensional radiation treatment
planning, limiting the radiation dose to lymph nodes draining
the upper extremity. Although merely a feasibility study, this
concept adds to the potential possibilities for further risk
reduction of lymphedema, but clearly more study is needed as
it is likely to be subject to similar limitations as the ARM
The number of breast cancer survivors is continuing to
increase, and issues of survivorship are being pushed to the
forefront of breast cancer research. Lymphedema is a feared
complication of breast cancer treatment because it is
unpredictable and chronic. Although lymphedema is primar-
ily defined as swelling of the upper extremity due to the
accumulation of protein-rich fluids, other symptoms, includ-
ing musculoskeletal pain, paresthesias, and decreased
shoulder range of motion may exist concurrently. It is
difficult to accurately determine the incidence of lymphe-
dema; however, contemporary literature would suggest that it
ranges from 15% to 25% within 5 years after ALND and that it
is likely to rise to 40% or higher with longer follow-up. In
current series, most cases of lymphedema are mild. The
technique of SLNB has certainly reduced the morbidity
associated with axillary staging for breast cancer; however,
there remains a small but significant risk of measured
lymphedema ranging from 0% to 7%.
Risk factors associated with lymphedema are inconsistent
across studies, but most are related to the extent of axillary
surgery, axillary radiation, injury, or infection in the ipsilateral
upper extremity, and body weight. New data are accumulating
on lymphedema progression, suggesting that patients with
mild lymphedema (noticeable only to themselves) are three
times more likely to develop moderate or severe lymphedema.
In an effort to further reduce axillary morbidities, many have
proposed further changes to axillary management.
Nomograms predicting residual disease in non-sentinel
nodes are frequently used in clinical practice to determine
the need for completion ALND. Furthermore, reported trends
in axillary surgery demonstrate decreased rates of completion
ALND after positive SLNB for micrometastatic or isolated
tumor cell disease. Finally, current surgical research focuses
on risk-reducing techniques that may allow for more selective
nodal treatments, sparing the drainage pathways of the upper
extremity. However, all patients remain at risk for lymphe-
dema if axillary radiation is used.
Disclosure: The authors report no conflict of interest.
1. SEER Stat Fact Sheets. Breast Cancer. 2006. Available from: http:// (accessed January 2010).

2. Horner MJ, Ries LAG, Krapcho M, et al. SEER Cancer Statistics Review, 1975–

2006. Bethesda, MD: National Cancer Institute; 2009. Available from: (accessed January 201).

3. McLaughlin SA, Wright MJ, Morris KT, et al. Prevalence of lymphedema

in women with breast cancer 5 years after sentinel lymph node biopsy or

axillary dissection: patient perceptions and precautionary behaviors. J Clin

Oncol. 2008;26(32):5220–5226.

4. Petrek JA, Senie RT, Peters M, et al. Lymphedema in a cohort of breast

carcinoma survivors 20 years after diagnosis. Cancer. 2001;92(6):1368–


5. Norman SA, Localio AR, Potashnik SL, et al. Lymphedema in breast

cancer survivors: incidence, degree, time course, treatment, and

symptoms. J Clin Oncol. 2009;27(3):390–397.

6. Blanchard DK, Donohue JH, Reynolds C, et al. Relapse and morbidity in

patients undergoing sentinel lymph node biopsy alone or with axillary

dissection for breast cancer. Arch Surg. 2003;138(5):482–487; discussion


7. Haid A, Koberle-Wuhrer R, Knauer M, et al. Morbidity of breast cancer
patients following complete axillary dissection or sentinel node biopsy

only: a comparative evaluation. Breast Cancer Res Treat. 2002;73(1):31–36.

8. Hoe AL, Iven D, Royle GT, et al. Incidence of arm swelling following

axillary clearance for breast cancer. Br J Surg. 1992;79(3):261–262.

9. Ivens D, Hoe AL, Podd TJ, et al. Assessment of morbidity from complete

axillary dissection. Br J Cancer. 1992;66(1):136–138.

10. Leidenius M, Leivonen M, Vironen J, et al. The consequences of long-time

arm morbidity in node-negative breast cancer patients with sentinel node

biopsy or axillary clearance. J Surg Oncol. 2005;92(1):23–31.

11. Ozaslan C, Kuru B. Lymphedema after treatment of breast cancer. Am J

Surg. 2004;187(1):69–72.

12. Petrek JA, Heelan MC. Incidence of breast carcinoma-related lymphe-

dema. Cancer. 1998;83(12 Suppl American):2776–2781.

13. Rockson SG. Lymphedema. Am J Med. 2001;110(4):288–295.

14. Ronka R, von Smitten K, Tasmuth T, et al. One-year morbidity after

sentinel node biopsy and breast surgery. Breast. 2005;14(1):28–36.

15. Schijven MP, Vingerhoets AJ, Rutten HJ, et al. Comparison of morbidity

between axillary lymph node dissection and sentinel node biopsy. Eur J

Surg Oncol. 2003;29(4):341–350.

16. Schrenk P, Rieger R, Shamiyeh A, et al. Morbidity following sentinel

lymph node biopsy versus axillary lymph node dissection for patients

with breast carcinoma. Cancer. 2000;88(3):608–614.

17. Swenson KK, Nissen MJ, Ceronsky C, et al. Comparison of side effects

between sentinel lymph node and axillary lymph node dissection for

breast cancer. Ann Surg Oncol. 2002;9(8):745–753.

18. Werner RS, McCormick B, Petrek J, et al. Arm edema in conservatively

managed breast cancer: obesity is a major predictive factor. Radiology.


19. Norman SA, Miller LT, Erikson HB, et al. Development and validation of a

telephone questionnaire to characterize lymphedema in women treated

for breast cancer. Phys Ther. 2001;81(6):1192–1205.

20. Golshan M, Martin WJ, Dowlatshahi K. Sentinel lymph node biopsy

lowers the rate of lymphedema when compared with standard axillary

lymph node dissection. Am Surg. 2003;69(3):209–211; discussion 212.

Prevalence and treatment of lymphedema in breast cancer
EJCMO 2010; 2:(2). June 2010

                                                                               Page 6
21. Langer I, Guller U, Berclaz G, et al. Morbidity of sentinel lymph node

biopsy (SLN) alone versus SLN and completion axillary lymph node

dissection after breast cancer surgery: a prospective Swiss multicenter

study on 659 patients. Ann Surg. 2007;245(3):452–461.
22. Lucci A, McCall LM, Beitsch PD, et al. Surgical complications associated with

sentinel lymph node dissection (SLND) plus axillary lymph node dissection

compared with SLND alone in the American College of Surgeons Oncology

Group Trial Z0011. J Clin Oncol. 2007;25(24):3657–3663.

23. Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of

sentinel node biopsy versus standard axillary treatment in operable breast

cancer: the ALMANAC trial. J Natl Cancer Inst. 2006;98(9):599–609.

24. McLaughlin SA, Wright MJ, Morris KT, et al. Prevalence of lymphedema

in women with breast cancer 5 years after sentinel lymph node biopsy or

axillary dissection: objective measurements. J Clin Oncol. 2008;26(32):


25. Purushotham AD, Upponi S, Klevesath MB, et al. Morbidity after sentinel

lymph node biopsy in primary breast cancer: results from a randomized

controlled trial. J Clin Oncol. 2005;23(19):4312–4321.

26. Rietman JS, Dijkstra PU, Geertzen JH, et al. Treatment-related upper limb

morbidity 1 year after sentinel lymph node biopsy or axillary lymph node

dissection for stage I or II breast cancer. Ann Surg Oncol. 2004;11(11):1018–


27. Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel

lymphadenectomy for breast carcinoma. Cancer. 2001;92(4):748–752.

28. Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of

sentinel-node biopsy with routine axillary dissection in breast cancer. N

Engl J Med. 2003;349(6):546–553.

29. Wilke LG, McCall LM, Posther KE, et al. Surgical complications

associated with sentinel lymph node biopsy: results from a prospective

international cooperative group trial. Ann Surg Oncol. 2006;13(4):491–


30. Hinrichs CS, Watroba NL, Rezaishiraz H, et al. Lymphedema secondary to

postmastectomy radiation: incidence and risk factors. Ann Surg Oncol.


31. Kiel KD, Rademacker AW. Early-stage breast cancer: arm edema after

wide excision and breast irradiation. Radiology. 1996;198(1):279–283.

32. Herd-Smith A, Russo A, Muraca MG, et al. Prognostic factors for

lymphedema after primary treatment of breast carcinoma. Cancer. 2001;


33. Paskett ED, Naughton MJ, McCoy TP, et al. The epidemiology of arm and

hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol

Biomarkers Prev. 2007;16(4):775–782.

34. Pierquin B, Mazeron JJ, Glaubiger D. Conservative treatment of breast

cancer in Europe: report of the Groupe Europeen de Curietherapie.

Radiother Oncol. 1986;6(3):187–198.

35. Bentzen SM, Dische S. Morbidity related to axillary irradiation in the

treatment of breast cancer. Acta Oncol. 2000;39(3):337–347.

36. Coen JJ, Taghian AG, Kachnic LA, et al. Risk of lymphedema after
regional nodal irradiation with breast conservation therapy. Int J Radiat

Oncol Biol Phys. 2003;55(5):1209–1215.

37. Meek AG. Breast radiotherapy and lymphedema. Cancer. 1998;83(12 Suppl


38. van der Veen P, De Voogdt N, Lievens P, et al. Lymphedema development

following breast cancer surgery with full axillary resection. Lymphology.


39. Ververs JM, Roumen RM, Vingerhoets AJ, et al. Risk, severity and

predictors of physical and psychological morbidity after axillary lymph

node dissection for breast cancer. Eur J Cancer. 2001;37(8):991–999.

40. Yang PS, Chen CM, Liu MC, et al. Radiotherapy can decrease locoregional

recurrence and increase survival in mastectomy patients with T1 to T2

breast cancer and one to three positive nodes with negative estrogen

receptor and positive lymphovascular invasion status. Int J Radiat Oncol

Biol Phys. 2009 Jul 3. Epub ahead of print. PubMed ID number is


41. Purushotham AD, Bennett Britton TM, Klevesath MB, et al. Lymph node

status and breast cancer-related lymphedema. Ann Surg. 2007;246(1):42–45.

42. Starritt EC, Joseph D, McKinnon JG, et al. Lymphedema after complete

axillary node dissection for melanoma: assessment using a new, objective

definition. Ann Surg. 2004;240(5):866–874.

43. Tsai RJ, Dennis LK, Lynch CF, et al. The risk of developing arm

lymphedema among breast cancer survivors: a meta-analysis of treatment

factors. Ann Surg Oncol. 2009;16(7):1959–1972.

44. Bar Ad V, Cheville A, Solin LJ, et al. Time course of mild arm lymphedema

after breast conservation treatment for early-stage breast cancer. Int J

Radiat Oncol Biol Phys. 2010;76(1):85–90.

45. Naik AM, Fey J, Gemignani M, et al. The risk of axillary relapse after

sentinel lymph node biopsy for breast cancer is comparable with that of

axillary lymph node dissection: a follow-up study of 4008 procedures.

Ann Surg. 2004;240(3):462–468; discussion 468–471.

46. Pernas S, Gil M, Benitez A, et al. Avoiding axillary treatment in sentinel

lymph node micrometastases of breast cancer: a prospective analysis of

axillary or distant recurrence. Ann Surg Oncol. 2010;17(3):772–7.

47. Cserni G, Gregori D, Merletti F, et al. Meta-analysis of non-sentinel node

metastases associated with micrometastatic sentinel nodes in breast

cancer. Br J Surg. 2004;91(10):1245–1252.

48. Kim T, Giuliano AE, Lyman GH. Lymphatic mapping and sentinel lymph

node biopsy in early-stage breast carcinoma: a metaanalysis. Cancer. 2006;


49. Hwang RF, Krishnamurthy S, Hunt KK, et al. Clinicopathologic factors

predicting involvement of nonsentinel axillary nodes in women with

breast cancer. Ann Surg Oncol. 2003;10(3):248–254.

50. Samoilova E, Davis JT, Hinson J, et al. Size of sentinel node tumor
deposits and extent of axillary lymph node involvement: which breast

cancer patients may benefit from less aggressive axillary dissections? Ann

Surg Oncol. 2007;14(8):2221–2227.

51. Viale G, Maiorano E, Pruneri G, et al. Predicting the risk for additional

axillary metastases in patients with breast carcinoma and positive sentinel

lymph node biopsy. Ann Surg. 2005;241(2):319–325.

52. Coutant C, Olivier C, Lambaudie E, et al. Comparison of models to

predict nonsentinel lymph node status in breast cancer patients with

metastatic sentinel lymph nodes: a prospective multicenter study. J Clin

Oncol. 2009;27(17):2800–2808.

53. Van Zee KJ, Manasseh DM, Bevilacqua JL, et al. A nomogram for

predicting the likelihood of additional nodal metastases in breast cancer

patients with a positive sentinel node biopsy. Ann Surg Oncol. 2003;10(10):


54. Bilimoria KY, Bentrem DJ, Hansen NM, et al. Comparison of sentinel

lymph node biopsy alone and completion axillary lymph node dissection

for node-positive breast cancer. J Clin Oncol. 2009;27(18):2946–2953.

55. Martelli G, Boracchi P, De Palo M, et al. A randomized trial comparing

axillary dissection to no axillary dissection in older patients with T1N0

breast cancer: results after 5 years of follow-up. Ann Surg. 2005;242(1):1–

6; discussion 7–9.

56. Stout Gergich NL, Pfalzer LA, McGarvey C, et al. Preoperative assessment

enables the early diagnosis and successful treatment of lymphedema.

Cancer. 2008;112(12):2809–2819.

57. Cornish BH, Chapman M, Hirst C, et al. Early diagnosis of lymphedema

using multiple frequency bioimpedance. Lymphology. 2001;34(1):2–11.

58. National Lymphedema Network Medical Advisory Committee: Training

of lymphedema therapies. Position statement of the National

Lymphedema Network. 2005. Available from:

pdfDocs/nlntraining.pdf (accessed March 18, 2010).

59. Hamner JB, Fleming MD. Lymphedema therapy reduces the volume of

edema and pain in patients with breast cancer. Ann Surg Oncol. 2007;14(6):


60. Koul R, Dufan T, Russell C, et al. Efficacy of complete decongestive

therapy and manual lymphatic drainage on treatment-related

lymphedema in breast cancer. Int J Radiat Oncol Biol Phys. 2007;67(3):


61. McKenzie DC, Kalda AL. Effect of upper extremity exercise on secondary

lymphedema in breast cancer patients: a pilot study. J Clin Oncol. 2003;


62. Mondry TE, Riffenburgh RH, Johnstone PA. Prospective trial of complete

decongestive therapy for upper extremity lymphedema after breast cancer

therapy. Cancer J. 2004;10(1):42–48; discussion 17–19.

63. Vignes S, Porcher R, Arrault M, et al. Long-term management of breast
cancer-related lymphedema after intensive decongestive physiotherapy.

Breast Cancer Res Treat. 2007;101(3):285–290.

European Journal of Clinical & Medical Oncology
EJCMO 2010; 2:(2). June 2010

                                                                                    Page 7
64. Ahmed RL, Thomas W, Yee D, et al. Randomized controlled trial of

weight training and lymphedema in breast cancer survivors. J Clin Oncol.


65. Sagen A, Karesen R, Risberg MA. Physical activity for the affected limb

and arm lymphedema after breast cancer surgery. A prospective,

randomized controlled trial with two years follow-up. Acta Oncol. 2009;


66. Schmitz KH, Ahmed RL, Troxel A, et al. Weight lifting in women with

breast-cancer-related lymphedema. N Engl J Med. 2009;361(7):664–673.

67. Boneti C, Korourian S, Diaz Z, et al. Scientific Impact Award: axillary

reverse mapping (ARM) to identify and protect lymphatics draining the

arm during axillary lymphadenectomy. Am J Surg. 2009;198(4):482–487.

68. Nos C, Lesieur B, Clough KB, et al. Comments to the letter to the editor

by Dr. Ponzone.Ann Surg Oncol 2008;15:392–393.

69. Ponzone R, Cont NT, Maggiorotto F, et al. Extensive nodal disease may

impair axillary reverse mapping in patients with breast cancer. J Clin

Oncol. 2009;27(33):5547–5551.

70. Ponzone R, Mininanni P, Cassina E, et al. Axillary reverse mapping in

breast cancer: can we spare what we find? Ann Surg Oncol. 2008;15(1):390–

391; author reply 392–393.

71. Thompson M, Korourian S, Henry-Tillman R, et al. Axillary reverse

mapping (ARM): a new concept to identify and enhance lymphatic

preservation. Ann Surg Oncol. 2007;14(6):1890–1895.

72. Kang SH, Choi JE, Jeon YS, et al. Preservation of lymphatic drainage from

arm in breast cancer surgery: is it safe? Cancer Res. 2009;69(201 Suppl 2).

73. Bedrosian I, Babiera GV, Mittendorf EA, et al. A phase-I study to assess

the feasibility and oncologic safety of axillary reverse mapping in breast

cancer patients. Abstract #220. ASCO Breast Cancer Symposium, San

Antonio, TX, October 8–10, 2009.

74. Cheville AL, Das I, Srinivas S, et al. A pilot study to assess the utility of

SPECT/CT-based lymph node imaging to localize lymph nodes that drain

the arm in patients undergoing treatment for breast cancer. Breast Cancer

Res Treat. 2009;116(3):531–538.

75. Barranger E, Dubernard G, Fleurence J, et al. Subjective morbidity and

quality of life after sentinel node biopsy and axillary lymph node

dissection for breast cancer. J Surg Oncol. 2005;92(1):17–22.
76. Ferreira BP, Pimentel MD, Santos LC, et al. [Morbidity after sentinel node

biopsy and axillary dissection in breast cancer]. Rev Assoc Med Bras. 2008;


77. Yen TW, Fan X, Sparapani R, et al. A contemporary, population-based

study of lymphedema risk factors in older women with breast cancer. Ann

Surg Oncol. 2009;16(4):979–988.

Prevalence and treatment of lymphedema in breast cancer
EJCMO 2010; 2:(2). June 2010

To top