Body Mass Index as a Major Risk Factor for Severe Breast Cancer-Related Lymphedema

Abstract

Background:

A few studies have examined the characteristics of severe breast cancer-related lymphedema (BCRL). This study aims at analyzing the factors associated with severe lymphedema (LE) across a specific population of patients with BCRL.

Methods and Results:

Seventy-four patients with BCRL were included and cared for in the Lymphology Unit of Toulouse University Hospital between 2015 and 2016. Characteristics of patients and factors related to severe BCRL were retrospectively assessed. The median age at time of LE was 56 years (30–82). Thirty-five patients (47.3%) had a mastectomy and 72 (97.3%) an axillary lymphadenectomy. Among patients treated with radiation therapy (n = 72), 76.3% received lymphatic nodes irradiation. Fifty-five patients (74.3%) received chemotherapy and 52 (70.3%) a hormonal suppression therapy. A high proportion of patients had severe (>400 mL, 64.9%) and premature LE, with a median time of 13 months since onset of surgery (0.1–400.2). Weight gain between surgery and LE management was more prevalent in obese patients (p = 0.0164). Body mass index (BMI) at BCRL diagnosis was the only risk factor associated with severe LE (p = 0.0132). There was no significant association between LE severity and treatments received for breast cancer.

Conclusions:

Our study did not show any influence of tumor characteristics and cancer-related treatments on the severity of BCRL. Only BMI at BCRL diagnosis appears as a factor related to severe LE. These results highlight the importance of an education care unit promoting personalized nutritional lifestyle and encouraging physical activity early in the management of breast cancer.

Introduction

Arm lymphedema (LE) was reported as the most frequent late outcome and complication that influenced breast cancer (BC) patients' quality of life.^1,2 The incidence of breast cancer-related lymphedema (BCRL) was about 20%.³ Currently, the gold standard of treatment was complete decongestive therapy (CDT).^4,5

Almost all studies analyzed risk factors for incident LE after BC. First, surgical factors were identified, as axillary-lymph-node dissection (ALND) and mastectomy, which had a strong level of evidence for LE onset.^3,6 Indeed, dissected axillary lymph nodes >10 appeared to be an independent risk factor for LE.^3,7 On the contrary, immediate implant reconstruction had the potential to reduce the risk of BCRL.⁸ The radiation therapy (RT), especially including ganglionic chains, was identified as an important risk factor for BCRL.⁹ The incidence of BCRL had reached 21.9% in women with RT including supraclavicular area versus 3.1% in those with breast or chest wall irradiation in a study of 1501 BC.¹⁰

Regarding systemic treatments, patients who received an adjuvant taxane-based chemotherapy were about three times more likely to develop BCRL than patients who did not receive chemotherapy¹¹ but the influence of taxane-based chemotherapy on BCRL remained unclear. Recently, a study seemed to demonstrate that estrogen influenced the management of the lymphatic system and provided more evidence that secondary LE was worsened by hormone therapy.¹²

Independently of BC-related treatments, skin infection and previous infection or inflammation on the ipsilateral arm were potential risk factors for LE.¹³ Further, obese patients had a higher risk of BCRL compared with nonobese patients. Significant postoperative changes in body weight (weight gain or weight loss) were also associated with an increased risk of BCRL.¹⁴

All these observational data stated that BC-related treatments and obesity were risk factors for the development of LE after BC. Most studies focused on the risk factors of BCRL occurrence, regardless of the severity of LE. This study aimed at identifying the factors associated with severe BCRL.

Materials and Methods

Study design

Patients diagnosed for BCRL who had been cared for at the Lymphology Unit of Toulouse University Hospital between 2015 and 2016 were included in this retrospective cohort study. Eligible patients had a history of unilateral nonmetastatic BC and a clinical diagnosis of BCRL, were not actively treated, and had no current evidence of cancer. LE was defined as a difference in the circumference (more than 2 cm) and/or volume (more than 200 mL or 10%) between the affected limb and the unaffected limb according to the International Society of Lymphology (ISL).¹⁵

Patients were treated with CDT, in two phases. All patients were involved in the health care approach between the Lymphology Unit and the Institute of University Cancer of Toulouse, and there was an integration of the therapeutic and educational programs. During the decongestive phase, patients were treated by experienced physical therapists with manual lymphatic drainage, compressive wrapping, exercises, and skin care. First, this decongestive phase was intended to reduce the volume of the LE and second, the maintenance phase aimed at maintaining the volumetric gain by self-bandaging and self-care.

The following clinical data were collected retrospectively: age, weight, height, body mass index (BMI) (kg/m²), weight fluctuations and delay between surgery and onset of LE, cardiovascular disease, occlusive disease of the artery, deep vein thrombosis, erysipelas, and osteoarticular disorders of the upper limb.

Assessment and treatments of arm lymphedema

The main clinical parameters used to diagnose a significant LE included a clinical upper limb edema with a volume difference between the upper affected limb and the other upper limb of 10% or 200 mL. Measurements were taken by two physical therapists experienced in LE treatment. Volumes were calculated by the same two physical therapists, after taking patient measurements every 5 cm, above (four measurements) and below (four measurements) the fold of the elbow (start point) and using the truncated cone formula: $\begin{matrix} H \times (C^{2} + C \times c + c^{2}) ∕ 12 π, \\ H = c o n e h e i g h t, \\ C = c o n e t o p c i r c u m f e r e n c e, \\ c = c o n e b a s e c i r c u m f e r e n c e . \end{matrix}$

The stage and the severity grade of LE according to the classification of the ISL,¹⁵ the localization, the potential complications, and the treatments received were collected.^16,17

Breast cancer histological characteristics and treatments

We recorded modalities of surgery of the breast with mastectomy or breast conservative surgery and axillary expertise with ALND or sentinel-lymph-node-biopsy (SLNB). Tumor characteristics such as histological type, grade, tumor size, hormone receptor status and human epidermal growth factor receptor-2 (HER2) status, and presence or absence of vascular invasion were recorded as well as the number of dissected lymph nodes and the number of positive lymph nodes for metastases.

Different systemic therapeutics used in the breast treatment were recorded: 1/chemotherapy with the sequence of the treatment, neoadjuvant or adjuvant chemotherapy, and the drugs used (5-fluorouracil, epirubicin, cyclophosphamide, and taxane), 2/hormonal suppression therapy (HST) using a Selective Estrogen Receptor Modulator (SERM) or an aromatase inhibitor (AI), 3/targeted therapy with trastuzumab. The locoregional treatment with the RT was recorded, and radiation fields were specified: breast or chest wall, supraclavicular region, infraclavicular region, internal mammary lymph nodes, and axillary region.

Statistical analysis

Continuous variables were represented as median with range (min–max). Qualitative variables were expressed as frequency with percentage. Association between limb volume and participants' characteristics were analyzed to determine risk factors of severe BCRL. Regarding qualitative variables, groups were compared by using chi-squared test or Fischer's exact test. The comparison between groups for quantitative variables required Kruskal Wallis' test. Statistics were performed by using STATA version 13 software (StataCorp, TX). Statistical significance was defined as a p-value <0.05.

Results

Patients' characteristics

Seventy-four patients (72 women and 2 men) who underwent clinical management for BCRL in Toulouse University Hospital with complete clinical data were included in this study.

The median age at time of LE diagnosis was 56 years (30–82). Nine patients (12.2%) had a history of cardiovascular disease, four patients had a history of erysipelas, and three patients experienced osteoarticular disorders of the upper limb. None experienced venous thromboembolic events of the affected upper limb, and none had arterial disease of the affected upper limb. The median BMI at time of clinical care for LE was 27.8 kg/m² (19.3–45.8). Twenty-five patients were overweight (41.7%), and 19 were obese (31.7%).

Weight gain from surgery to LE clinical care was most important in obese patients (median of 3.5 kg [0.0–24.0]) than normal weight patients and overweight patients (0 kg [−5.0 to 6.0] and 0 kg [−3.0 to 8.0] respectively; p = 0.0164). Most of the obese patients (90%) tended to gain weight compared with normal weight patients (36.4%) or overweight patients (35.7%) (p = 0.0481).

Treatments for breast cancer

Clinical characteristics of BC, locoregional, and systemic treatments are reported in Table 1. Among patients with mastectomy, nine had a reconstruction of whom five had mammary implants and four had tissue flap procedure. Patients were operated between July 1979 and April 2015. The median number of dissected lymph nodes was 13 (2–25.0). Forty-seven patients (63.5%) had at least one positive lymph node(s). Among these patients, 14 patients (29.8%) had 4–9 positive lymph nodes. Twenty-one patients (32.3%) showed lymph node(s) with capsule disruption.

Table 1.

Tumor Characteristics and Treatments for Breast Cancer in 74 Patients

Characteristics and treatments for breast cancer	n (%)
Type of surgery
Mastectomy	35 (47.3)
Breast conservative surgery	39 (52.7)
Axillary lymph node dissection	72 (97.3)
Sentinel lymph node biopsy	2 (2.7)
Number of dissected axillary lymph nodes^a
≤10	17 (23.9)
11–20	47 (66.2)
≥21	7 (9.9)
Grade^a
1	6 (8.5)
2	34 (47.9)
3	31 (43.7)
pT^a
T1	38 (53.5)
T2	20 (28.2)
T3	8 (11.3)
T4	5 (7.0)
pN^a
N0	26 (35.6)
N1	30 (41.1)
N2	14 (19.2)
N3	3 (4.1)
Chemotherapy
Not done	19 (25.7)
Neoadjuvant chemotherapy	8 (10.8)
Adjuvant chemotherapy	46 (62.2)
Both	1 (1.4)
Radiation therapy
Not done	2 (2.7)
Done	72 (97.3)
Breast^a	39 (66.1)
Chest wall^a	20 (33.9)
Supra-clavicular and internal mammary lymph nodes^a	21 (35.6)
Supra-clavicular, internal mammary, and infra-clavicular lymph nodes ± axillary region^a	24 (40.7)
Hormonal suppression therapy
No	22 (29.7)
Yes	52 (70.3)

The number of patients could vary depending on data availability.

Fifty-five patients (74.3%) received chemotherapy. The most frequent chemotherapy protocol was three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide and three cycles of taxotere (69.8%). Trastuzumab was administered in conjunction with chemotherapy in 10 patients (13.7%) with tumor HER2 positive expression.

Thirty-five patients (67.3%) received an HST with a SERM with a median duration of therapy of 3 years (1.0–7.0), and 29 patients (61.7%) received an AI with a median duration of therapy of 5 years (2.0–5.0). Twenty-one patients carried on receiving an HST at the date of latest news.

Twenty-eight patients (45.2%) received chemotherapy before the appearance of LE, 4 patients (6.5%) received an HST, and 21 patients (33.9%) received an association of chemotherapy and HST.

Characteristics of LE and severity risk factors

Most patients (96.8%) presented with stage 2 LE according to the classification of the ISL. LE occurred quickly from surgery with a median time of 13 months (0.1–400.2). Forty-eight patients (66.7%) had an LE onset 2 years after surgery. LE was considered as severe in 64.9% of cases (volume of edema >400 mL). It was located at the forearm, the arm, the hand, and the fingers in, respectively, 94.6%, 77%, 64.9%, and 36.5% of cases. Patients suffered from axillary web syndrome in 34.3% of cases and limb heaviness in 31.3% of cases. Patients also complained about motion restriction and pain in the upper limb (respectively in 20.6% and 16.4% of cases).

All patients were treated with the CDT and self-care. In the maintenance phase, all patients wore a daytime compression. Seventy-one patients (95.9%) wore garment compression class 3 (30 mmHg), 52 patients (70.3%) did regular multilayer bandaging, and 40 patients (55.6%) had nighttime compression therapy. Forty-eight patients (73.8%) did physical activity during their management for LE.

BMI at BCRL onset was the only significant parameter related to severity of LE (Table 2). Neither age nor weight fluctuation between surgery and BCRL onset was significantly related to severity of LE. There was no significant association between LE severity and treatments received for BC (Table 3).

Table 2.

Age, Body Mass Index, Weight Fluctuation, and Severity of Breast Cancer-Related Lymphedema

	Overall population, n (%)	LE <200 mL (n = 10), n (%)	LE 200–400 mL (n = 16), n (%)	LE >400 mL (n = 48), n (%)	p
Age at BCRL onset					0.327
<50 years	18 (24.7)	4 (44.4)	3 (18.8)	11 (22.9)
≥50 years	55 (75.3)	5 (55.6)	13 (81.3)	37 (77.1)
BMI (kg/m²) at BCRL onset					0.0132
17–25	16 (26.7)	2 (33.3)	4 (28.6)	10 (25.0)
25–30	25 (41.7)	2 (33.3)	10 (71.4)	13 (32.5)
≥30	19 (31.7)	2 (33.3)	0 (0.0)	17 (42.5)
Weight fluctuation between surgery and BCRL onset					0.2099
Weight loss	10 (27.8)	0 (0.0)	5 (45.5)	5 (25.0)
No change	8 (22.2)	2 (40.0)	3 (27.3)	3 (15.0)
Weight gain	18 (50.0)	3 (60.0)	3 (27.3)	12 (60.0)

BCRL, breast cancer-related lymphedema; BMI, body mass index; LE, lymphedema.

Table 3.

Cancer Treatments, Clinical Characteristics, and Severity of Breast Cancer-Related Lymphedema

	LE <400 mL (n = 25), n (%)	LE ≥400 mL (n = 49), n (%)	p
Treatment for cancer
Surgery			0.9311
Mastectomy	12 (48.0)	23 (46.9)
Tumorectomy	13 (52.0)	26 (53.1)
Axillary expertise
Sentinel lymph node biopsy	2 (8.0)	0 (0.0)
Axillary-lymph node dissection	23 (92.0)	49 (100.0)
Dissected axillary lymph nodes			0.7912
≤10	6 (26.1)	11 (22.9)
10–20	14 (60.9)	33 (68.8)
≥21	3 (13.0)	4 (8.3)
Neo-adjuvant chemotherapy and/or adjuvant chemotherapy
No	5 (20.0)	14 (28.6)
Neo-adjuvant	4 (16.0)	4 (8.2)
Adjuvant	16 (64.0)	30 (61.2)
Both	0 (0.0)	1 (2.0)
Radiation therapy (n = 59)			0.4679
Without lymph node irradiation	6 (26.1)	8 (22.2)
With IM or SC irradiation	6 (26.1)	15 (41.7)
With IC or axillary irradiation	11 (47.8)	13 (36.1)
Hormonal suppression therapy			0.7602
No	8 (32.0)	14 (28.6)
Yes	17 (68.0)	35 (71.4)
Tumor grade
Grade			0.7099
1	1 (4.0)	5 (10.9)
2	13 (52.0)	21 (45.7)
3	11 (44.0)	20 (43.5)
pN			0.7279
N0	8 (32.0)	18 (37.5)
N1	10 (40.0)	20 (41.7)
N2	5 (20.0)	9 (18.8)
N3	2 (8.0)	1 (2.1)
Lymphedema clinical characteristics
Delay from surgery to lymphedema onset (months)			0.6715
Median (range)	13.0 (0.9–189.7)	11.4 (0.1–400.2)
Erysipelas			0.2439
No	23 (95.8)	37 (84.1)
Yes	1 (4.2)	7 (15.9)
Decrease articular amplitude			0.5288
No	17 (73.9)	37 (82.2)
Yes	6 (26.1)	8 (17.8)

IC, infra-clavicular; IM, internal mammary; SC, supra-clavicular.

Discussion

The presented results highlight that neither tumor characteristics nor cancer-related treatments are associated with severity of BCRL. In our patients' cohort, only BMI at BCRL onset appears related to the severity of LE. According to the American Cancer Society guidelines, maintaining normal weight through an active and healthy lifestyle is part of the treatment of BCRL.¹⁸ Our results highlight the importance of an education care unit promoting personalized nutritional lifestyle and encouraging physical activity early in the management of BC.

A French study, published by Vignes et al., including 807 patients with an ALND, found that BMI, duration of LE, delay between BC and LE occurrence, history of cellulitis, and mastectomy were correlated to the volume of LE. The authors did not show any influence of RT, chemotherapy, and HST on the severity of BCRL.¹⁹ In 2015, a U.S. study showed that, in 50 patients with a median BMI of 32.9 kg/m², age older than 50 years and grade-3 tumor were considered as severity risk factors of LE.²⁰

In our population, median BMI at time of clinical care for LE was 27.8 kg/m². Weight gain from surgery to LE clinical care was the most important in obese patients compared with normal weight and overweight patients. Usually, high BMI (at diagnosis, BMI ≥30 kg/m²) and weight fluctuations were frequently considered as risk factors for LE development.^3,21,22 Jammallo et al. reported on a cohort of 787 patients who were prospectively screened for BCRL via perometry that BMI ≥30 kg/m² was an independent risk factor for BCRL. Weight fluctuations (loss or gain) >10 pounds per month postoperatively also resulted in a higher risk of BCRL.¹⁴ However, weight gain was not significantly associated with the severity of BCRL in our population.

Treatments for BC could explain BCRL. In our study, about half of the patients had a mastectomy (47.3%) and all the patients, except 2, had ALND. These results followed the same trends as other studies observing that ALND and mastectomy had a strong level of evidence for BCRL.^3,6,23,24 In fact, Miller et al. highlighted an increased incidence of LE in 627 patients who underwent a mastectomy, after ALND with or without RT (30.1% and 19.3%, respectively) compared with SLNB (<10%).²⁵ Our population seemed to be representative of other cohorts with the same risk factors as ALND and RT.^6,21 Moreover, the number of dissected lymph nodes was high with a median of 13 nodes. However, no significant association was found between LE severity and surgical management of cancer.

LE onset is not only a side effect of the surgery but also appears to be highly dependent on cancer treatments. In our study, among patients treated with RT (n = 72), 76.3% received lymphatic node irradiation. Indeed, in a recent meta-analysis, irradiation of the locoregional ganglionic chains in addition to the irradiation of the breast or the chest wall increased the risk of LE (odds ratio [OR] = 2.85, 95% confidence interval [CI]: 1.24–6.55). The authors identified that, in patients who underwent an SLNB, there was no significant increase of the risk of LE with the addition of an irradiation of the ganglionic chains (OR = 1.58, 95% CI: 0.54–4.66). In contrast, in patients treated by ALND, the addition of an irradiation of the ganglionic chains and an irradiation of the breast or the chest wall significantly increased the risk of LE (OR = 2.74, 95% CI: 1.38–5.44).⁹

Consequently, in our population, BCRL was considered as severe (volume of edema >400 mL) in 48 patients (64.9%) and with early occurrence with a median time of onset of LE of 13 months after surgery. The high proportion of patients who experienced ALND and RT, including irradiation of lymph node areas, may explain these findings.^3,6,26 In line with previously published data, RT did not appear as a risk factor for severe LE in the present population.¹⁹

Regarding systemic treatments, chemotherapy might influence incidence of BCRL, especially taxane-based chemotherapy. In fact, Nguyen et al. analyzed different drugs of chemotherapy and observed that taxane-based chemotherapy conferred the highest increase in BCRL risk, with or without anthracyclines; whereas anthracyclines without taxanes showed a smaller but still significant increase in risk compared with no chemotherapy.²³ Swaroop et al. evidenced that ALND, high BMI, and older age at surgery were significantly associated with a high risk of BCRL; whereas taxane-based chemotherapy was not significant in comparison with no chemotherapy.²⁷

In our study, we did not highlight any influence of chemotherapy on the severity of LE. In fact, the higher incidence of LE in women who experienced ALND appears not only due to the addition of RT, and chemotherapy, but also due to obesity.²³ Experimental data suggest that HST with SERM, which is usually initiated postoperatively for a period of 5 years, could worsen LE.¹² However, HST seemed to have no effect on the severity of BCRL in our cohort.

BCRL is a chronic complication that negatively affects patients' body image and quality of life after BC.^2,28 In our study, symptoms such as heaviness and complications as an axillary bridle were found around within a quarter of the patients. Only 11.8% of patients had erysipelas and 16.4% had pain, which might predict LE morbidity.^28,29 In other studies, symptoms such as osteoarticular lesions or infectious complications were more frequent around 30% or even 40%.³⁰ An education care unit could explain the decrease of these complications, promoting advice to avoid cellulitis, hygieno-dietetic rules, physical activity, and compression therapy, allowing better control of lymphatic pathology.

Even though water volumetry is considered the reference measurement instrument for assessing upper limb LE,³¹ utilization of volumetric measures according to French recommendations³² represents a strength of this study, reporting precise and reliable data.^33,34 Our study has limitations common to cross-sectional design, especially in establishing cause–effect relationships between clinical parameters, treatments, and severity of BCRL. Further, BC treatments are multimodal in nature and many patients underwent a combination of therapies. Our results pointed out the clinical relevance of BMI early in the prevention of BCRL and should be confirmed in a large-scale study.

Conclusion

The presented results highlight the impact of overweight on the severity of BCRL, with no influence on cancer characteristics or cancer-related treatments. The importance of weight control and physical activity may prevent the incidence of severe BCRL. Maintaining normal weight or initiating weight loss for those patients who are overweight or obese are significant parts of the individual tailored exercise program that is recommended by the American Cancer Society guidelines to prevent BCRL.¹⁸ Education care unit plays a strong role in the management of this pathology to offer personalized care management for each patient.

Footnotes

Acknowledgments

The authors thank the multidisciplinary team of Lymphology Department of the Toulouse University Hospital (physiotherapists: Y. Smati, N. Elkamil; therapeutic education nurse: K. Faucher, dietician: K. Espitalier, psychologist: H. Bengrouba) and the Sport Medicine Department of the Toulouse University Hospital, France (Pr D. Rivière).

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was not supported by any funding.

References

Ahmed

, Prizment

, Lazovich

, Schmitz

, Folsom

. Lymphedema and quality of life in breast cancer survivors: The Iowa Women's Health Study. J Clin Oncol, 2008; 26:5689–5696.

Taghian

, Miller

, Jammallo

, O'Toole

, Skolny

. Lymphedema following breast cancer treatment and impact on quality of life: A review. Crit Rev Oncol Hematol, 2014; 92:227–234.

DiSipio

, Rye

, Newman

, Hayes

. Incidence of unilateral arm lymphoedema after breast cancer: A systematic review and meta-analysis. Lancet Oncol, 2013; 14:500–515.

Vignes

, Porcher

, Arrault

, Dupuy

. Long-term management of breast cancer-related lymphedema after intensive decongestive physiotherapy. Breast Cancer Res Treat, 2007; 101:285–290.

Vignes

. [Lymphedema: From diagnosis to treatment]. Rev Med Interne, 2017; 38:97–105.

Zou

, Liu

F-H

, Shen

P-P

, et al. The incidence and risk factors of related lymphedema for breast cancer survivors post-operation: A 2-year follow-up prospective cohort study. Breast Cancer, 2018; 25:309–314.

Kim

, Park

, Lee

, et al. Breast cancer-related lymphedema after neoadjuvant chemotherapy. Cancer Res Treat, 2015; 47:416–423.

Miller

, Colwell

, Horick

, et al. Immediate implant reconstruction is associated with a reduced risk of lymphedema compared to mastectomy alone: A prospective cohort study. Ann Surg, 2016; 263:399–405.

Shaitelman

, Chiang

Y-J

, Griffin

, et al. Radiation therapy targets and the risk of breast cancer-related lymphedema: A systematic review and network meta-analysis. Breast Cancer Res Treat, 2017; 162:201–215.

10.

Warren

LEG

, Miller

, Horick

, et al. The impact of radiation therapy on the risk of lymphedema after treatment for breast cancer: A prospective cohort study. Int J Radiat Oncol Biol Phys, 2014; 88:565–571.

11.

Cariati

, Bains

, Grootendorst

, et al. Adjuvant taxanes and the development of breast cancer-related arm lymphoedema. Br J Surg, 2015; 102:1071–1078.

12.

Morfoisse

, Tatin

, Chaput

, et al. Lymphatic vasculature requires estrogen receptor-α signaling to protect from lymphedema. Arterioscler Thromb Vasc Biol, 2018; 38:1346–1357.

13.

Asdourian

, Skolny

, Brunelle

, Seward

, Salama

, Taghian

. Precautions for breast cancer-related lymphoedema: Risk from air travel, ipsilateral arm blood pressure measurements, skin puncture, extreme temperatures, and cellulitis. Lancet Oncol, 2016; 17:e392–e405.

14.

Jammallo

, Miller

, Singer

, et al. Impact of body mass index and weight fluctuation on lymphedema risk in patients treated for breast cancer. Breast Cancer Res Treat, 2013; 142:59–67.

15.

International Society of Lymphology. The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology. Lymphology, 2013; 46:1–11.

16.

Campisi

, Boccardo

. Microsurgical techniques for lymphedema treatment: Derivative lymphatic-venous microsurgery. World J Surg, 2004; 28:609–613.

17.

Garza

, Skoracki

, Hock

, Povoski

. A comprehensive overview on the surgical management of secondary lymphedema of the upper and lower extremities related to prior oncologic therapies. BMC Cancer, 2017; 17:468.

18.

Runowicz

, Leach

, Henry

, et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J Clin Oncol, 2016; 34:611–635.

19.

Vignes

, Arrault

, Dupuy

. Factors associated with increased breast cancer-related lymphedema volume. Acta Oncol, 2007; 46:1138–1142.

20.

Coriddi

, Khansa

, Stephens

, Miller

, Boehmler

, Tiwari

. Analysis of factors contributing to severity of breast cancer-related lymphedema. Ann Plast Surg, 2015; 74:22–25.

21.

Ribeiro Pereira

ACP

, Koifman

, Bergmann

. Incidence and risk factors of lymphedema after breast cancer treatment: 10 years of follow-up. Breast, 2017; 36:67–73.

22.

, Axelrod

, Guth

, et al. Patterns of obesity and lymph fluid level during the first year of breast cancer treatment: A prospective study. J Pers Med, 2015; 5:326–340.

23.

Nguyen

, Hoskin

, Habermann

, Cheville

, Boughey

. Breast cancer-related lymphedema risk is related to multidisciplinary treatment and not surgery alone: Results from a large cohort study. Ann Surg Oncol, 2017; 24:2972–2980.

24.

Tsai

, Dennis

, Lynch

, Snetselaar

, Zamba

GKD

, Scott-Conner

. The risk of developing arm lymphedema among breast cancer survivors: A meta-analysis of treatment factors. Ann Surg Oncol, 2009; 16:1959–1972.

25.

Miller

, Specht

, Skolny

, et al. Risk of lymphedema after mastectomy: Potential benefit of applying ACOSOG Z0011 protocol to mastectomy patients. Breast Cancer Res Treat, 2014; 144:71–77.

26.

Kim

, Kim

, Lee

, et al. A model to estimate the risk of breast cancer-related lymphedema: Combinations of treatment-related factors of the number of dissected axillary nodes, adjuvant chemotherapy, and radiation therapy. Int J Radiat Oncol Biol Phys, 2013; 86:498–503.

27.

Swaroop

, Ferguson

, Horick

, et al. Impact of adjuvant taxane-based chemotherapy on development of breast cancer-related lymphedema: Results from a large prospective cohort. Breast Cancer Res Treat, 2015; 151:393–403.

28.

McWayne

, Heiney

. Psychologic and social sequelae of secondary lymphedema: A review. Cancer, 2005; 104:457–466.

29.

Dawes

, Meterissian

, Goldberg

, Mayo

. Impact of lymphoedema on arm function and health-related quality of life in women following breast cancer surgery. J Rehabil Med, 2008; 40:651–658.

30.

Vignes

, Coupé M, Baulieu F, Vaillant L, Groupe Recommandations de la Société Française de Lymphologie. [Limb lymphedema: Diagnosis, explorations, complications. French Lymphology Society]. J Mal Vasc, 2009; 34:314–322.

31.

Hidding

, Viehoff

, Beurskens

CHG

, van Laarhoven

HWM

, Nijhuis-van der Sanden

MWG

, van der Wees

. Measurement properties of instruments for measuring of lymphedema: Systematic review. Phys Ther, 2016; 96:1965–1981.

32.

Boulon

, Becker

, Vignes

. [How to quantify limb edema?]. J Mal Vasc, 2010; 35:163–168.

33.

Mori

, Lustman

, Katz-Leurer

. Self-measurement of upper extremity volume in women post-breast cancer: Reliability and validity study. Physiother Theory Pract, 2015; 31:283–287.

34.

Levenhagen

, Davies

, Perdomo

, Ryans

, Gilchrist

. Diagnosis of upper quadrant lymphedema secondary to cancer: Clinical practice guideline from the oncology section of the American Physical Therapy Association. Phys Ther, 2017; 97:729–745.