Five-Year Cumulative Incidence of Axillary Web Syndrome and Comparison in Upper Extremity Movement, Function, Pain, and Lymphedema in Breast Cancer Survivors With and Without Axillary Web Syndrome

Abstract

Objective:

To determine the cumulative incidence and natural history of axillary web syndrome (AWS) and its related postoperative risk for physical impairments in a cohort of women followed for 5 years post breast cancer surgery.

Design:

Prospective, longitudinal study

Setting:

Academic health center

Participants:

Women (n=36) with and without AWS following breast cancer surgery with sentinel node biopsy or axillary lymph node dissection

Interventions:

Not applicable.

Main Outcome Measures:

Participants were assessed for AWS, shoulder goniometric flexion and abduction range of motion (ROM), function (Disability of the Arm, Shoulder, and Hand), lymphedema (bioimpedance spectroscopy, girth measures, and tissue dielectric constant), and pain (visual analog scale) at 2-, 4-, 12-, and 78- weeks and 5-years after breast cancer surgery. Analysis of variance compared ROM, function, lymphedema, and pain in women identified with AWS to those without AWS across visits. Univariate logistic regression assessed if AWS was a risk factor for physical impairment at 5-years.

Results:

The cumulative incidence of AWS was 57%. Fifty percent (14/28) of the women that completed all study visits had signs of AWS at 5-years. Abduction active ROM was significantly lower in women with AWS at 2- and 4- weeks post-surgery. AWS was identified as a risk factor for reduced shoulder motion at 5-years. Regardless of AWS, 75% of the women experienced one or more upper extremity physical impairments at 5-years, which is an increase from 66% at 78-weeks in the same cohort.

Conclusions:

AWS is associated with reduced shoulder ROM in the early post-operative time period, can persist for 5-years after breast cancer surgery, and increases the risk of long-term reduced shoulder ROM. Long-term physical issues are apparent following breast cancer surgery regardless of AWS.

Advances in the treatment of breast cancer have resulted in increased survival rates and decreased mortality.¹ Nonetheless, there are morbidities that occur as a result of both cancer and the cancer treatment. Upper extremity complications include lymphedema, pain, and reduction in range of motion and function, all of which negatively impact quality of life.^2–4 An additional complication that is often overlooked is axillary web syndrome (AWS).⁵ Another term for AWS is cording, since its defining characteristic is the development of a tight cord or cords of tissue in the axillae that become apparent with shoulder abduction. Cords may extend down along the medial arm as distal as the thumb, and even along the chest wall.^5–7 The etiology of AWS has been thought to be iatrogenic damage to the lymphatic or venous system. A growing body of evidence has suggested that local pathophysiologic injury to the lymphatic system, is more likely than injury to the venous system.^5,6,8–12

AWS was once thought to be a benign, self-limited condition only occurring in the early postoperative period.^5,13 Our research represents a potential paradigmatic shift by refuting these ideas by demonstrating the chronicity of AWS.^14,15 We found that AWS can develop after the early postoperative time period, linger for months to years after surgery, and recur after resolution.^14,15 We demonstrated that AWS is associated with physical impairments including reduced upper extremity range of motion and dysfunction during the early postoperative time period (i.e. 12 weeks) and up to 18 months after surgery.^14,15 Other research demonstrated that AWS has been associated with increased upper extremity lymphedema circumferential volume measures.^16–18 Additionally, women with a lower BMI, more invasive surgery, and reduced shoulder range of motion have all been shown to be at higher risk for the development of AWS.^14–17 Our previous findings revealed the prevalence of AWS to be 47% and 50% at 12- and 78-weeks post-surgery, respectively.^14,15

The aims of this study were to 1) determine the 5-year cumulative incidence of AWS, 2) characterize the 5-year natural history in women with and without AWS post breast cancer surgery related to upper extremity range of motion, function, lymphedema, and pain, and 3) determine if AWS is a risk factor for long term physical impairments 5 years after surgery. We hypothesized that the cumulative incidence of AWS would increase over time and women with AWS would have more significant and have a higher risk of upper extremity range of motion, function, pain and lymphedema problems compared to women without AWS.

METHODS

This prospective, observational, longitudinal study followed women for 5 years after breast cancer surgery with visits at 2-, 4-, 12-, and 78-weeks; and with a long-term follow-up visit at 5-years. This human research study was approved by the University of Minnesota Internal Review Board for all visits. The women who completed all the previous visits were contacted by phone and asked if they would be willing to return for an additional follow-up.^14,15 Women who agreed to participate attended a 5-year follow-up visit and provided written consent prior to further study participation. Full details on the recruitment strategies for the original study have been previously published.^14,15 Subjects were consecutively recruited from a single academic health care center.

Women who underwent surgical breast cancer treatment (lumpectomy or mastectomy) with a minimum removal of one axillary lymph node (sentinel lymph node surgery or axillary lymph node dissection) were included in the study. Women who had undergone a prophylactic contralateral mastectomy were also allowed to participate. Women were excluded if they had previous surgery for breast cancer, synchronous bilateral breast cancer, previous history of shoulder surgery or dysfunction, or upper extremity deep vein thrombosis. Only women who participated in all of the previous study visits were allowed to return for the 5-year follow-up. Participants from the original study were eligible to participate in the 5-year follow-up regardless of cancer and/or rehabilitation treatment that was received.

Demographic data was collected using self-report forms and was validated using medical records. The methodology for the clinical outcome measures has been well described in the previous study and is summarized below.^14,15 A single assessor (LK) and study primary investigator (PI), a physical therapist and certified lymphedema therapist with over 15 years working with breast cancer survivors, took all the measures at each time point for the study.

Axillary Web Syndrome Assessment

The PI (LK) in the study assessed each patient for AWS at each visit as described in the previous literature.^14,15 Women were considered to have AWS if they had the presence of a visible or palpable cord of tissue in the axilla, upper extremity, or trunk during maximal shoulder abduction. This type of assessment has been validated, however, reliability has yet to be tested.¹⁹ AWS status was assessed after all the outcome measures were taken to reduce potential measuring bias.

Range of Motion

Active and passive range of motion (AROM, PROM) were measured bilaterally for shoulder flexion and abduction using a standard, reliable goniometric method.^20,21 Shoulder AROM was measured in a standing position. Shoulder PROM was measured supine. Full elbow extension was maintained during all shoulder range of motion measurements to avoid elbow flexion, which could potentially reduce tension on and obscure the AWS cords.

Function and Pain

The Disabilities of Arm, Shoulder, and Hand (DASH) self-report questionnaire measured upper extremity function through responses to questions about arm, shoulder and hand functional activities.²² DASH scores range from 0–100 with higher scores reflecting more dysfunction. The DASH questionnaire is a reliable and validated questionnaire recommended by the American Physical Therapy Association Clinical Practice Guidelines for measuring function in individuals with breast cancer.^23,24 The MCID for DASH is 10 for adults with musculoskeletal upper extremity problems.²⁵ DASH data was collected through a secure online survey in Research Electronic Data Capture (REDCAP) or a written questionnaire, per patient preference.

A visual analog scale (VAS) measured pain with movement in the affected arm.^14,15 The VAS for pain provided quantifiable, reliable measurements of pain ranging from 0–100, with 0 reflecting no pain and 100 indicating worst pain possible.²⁶ The VAS pain MCID is 10 points in individuals following surgery.²⁷

Lymphedema Measures

Participants underwent all of the following lymphedema measures at each visit. Utilizing multiple measures allowed for a more thorough assessment of the individual’s lymphedema status since lymphedema could be localized or diffuse depending on the participant’s presentation.

Upper extremity lymphedema measurements: Upper extremity lymphedema was measured using upper extremity circumferential measurements and bioimpedance spectroscopy (BIS). Upper extremity circumferential measurements were taken at 8 cm increments bilaterally starting at the ulnar styloid. Volume was calculated for each arm using the formula for a truncated cone, and volume differences between sides were used for analysis.^28–30 BIS (LDex U400, Impedimed, San Diego, California) measured the amount of extracellular fluid in the upper extremities. The device provides an L-Dex value, which accounts for the differences in extracellular fluid between affected and unaffected sides. A normal L-Dex range is between −10 to 10.³¹

Trunk measurement: Trunk lymphedema measures were taken using the MoisturemeterD (Delfin Technologies Ltd.,Kuopio Finland;www.delfintech.com), which measured local tissue water bilaterally on the trunk at a location 8 cm below the axillary fold. The MoisturemeterD provided the tissue dielectric constant (TDC) value, which is reflective of the amount of water in the tissue under the MoisturemeterD transducer head. TDC has been well described in other literature.^14,32,33 TDC ratio (TDC affected/TDC unaffected = TDC ratio) was calculated for assessment of trunk edema and data analysis.

Upper Extremity Physical Impairments:

A shoulder flexion or abduction AROM or PROM difference of >10 degrees between affected and unaffected sides was considered diagnostic for a reduced shoulder range of motion physical impairment based on previous research.^34–36 DASH scores >10.1 were identified as having an upper extremity functional physical impairment.³⁷ A pain level of >30 was indicative of a painful upper extremity physical impairment.^38,39 Upper extremity and trunk lymphedema was deemed present if a participant presented with one or more of the following criteria: an upper extremity volume difference of more than 10% or 200ml, a circumference difference of > 2cm, an L-Dex value >10, or a trunk TDC ratio of >1.2.^15,40

Rehabilitation

Rehabilitation treatment received within the 5 years, such as physical therapy and/or occupational therapy, was collected through self-report. Although this was a non-intervention study, the women were educated in lymphedema signs and symptoms as well as lymphedema precautions at 12 weeks following surgery.

Data Analysis

Descriptive statistics calculated the cumulative incidence of AWS at each visit and presence of AWS at 5 years. Women identified with AWS at any visit were included in the AWS group and those without AWS at any visit were included in the Non-AWS group for the statistical group analyses.

Chi squared or two sample student t-test were used to compare demographic data. Difference between the groups (AWS vs. Non-AWS) in the clinical outcome measures (ROM, pain, lymphedema measures, and function) were analyzed across time (2-, 4-, 12-, 78-weeks, and 5-years) using repeated measures ANOVA. A p-value of ≤ 0.05 was deemed significant. If the Mauchly test for homogeneity of variance was violated, the corrected Geisser-Greenhouse p-value was used. If an interaction existed, a Tukey-Kramer adjustment analyzed multiple comparisons. A univariate logistic regression was used to explore if AWS was a risk factor for long-term physical impairments of reduced range of motion, reduced function, pain, and lymphedema. A higher p value of 0.10 was chosen a priori with statistical consultation to avoid excluding a potentially important variable because the sample size was low. Analysis was performed using NCSS statistical program Version 9.0 (Kaysville, Utah). Descriptive statistics were used to describe the rehabilitation treatment that women received.

The original a priori sample size calculation of 36 has been previously published.^14,15 A sample size of 36 was calculated a priori to detect a 20 point difference in DASH scores between groups, which provided a power level of 0.95 at the 0.05 significance level. The DASH outcome was established as the primary outcome a priori. Assuming a 20% drop out rate, a sample size of 28 (1:1 ratio in each group) provided a power level of 0.80–0.85 at the 0.05 significance level (2-sided) to detect a difference of 9 in the DASH score with a standard deviation (SD) of 8. The estimated sample size for all other outcome measures have been previously published. ¹⁴

Yates’ Continuity Corrected Chi-Square Test (or Fisher’s exact) was used to assess treatment differences between groups.

RESULTS

Twenty-eight of 36 eligible women consented to and participated in the 5-year follow-up visit. Seven individuals were lost to follow-up (three at the 78-week and four at the 5-year timepoint) which was a 19% drop out rate. One participant was deceased at the 78-week timepoint. The reasons for loss to follow-up were four individuals moved away, two did not return a phone call, and one was too busy to participate. Of the eight participants lost to follow up, three individuals had AWS and five individuals did not have AWS at previous visits. Sixteen of the 28 women experienced AWS at least one time within 5-years making the cumulative incidence of AWS 47% at 12-weeks, 50% at 78 weeks, and 57% at 5-years. These 16 women were grouped into the AWS group for statistical analysis. The remaining 12 women that did not experience AWS at any time point were grouped into the Non-AWS group. At 5 years, 14 of the 28 women (50%) had signs of AWS (Fig. 1). One of these women had a new onset of AWS and had not shown signs of AWS at any of the previous visits. Five women had AWS at all 5 timepoints. Table 1 displays the participant characteristics of the 5-year study cohort. The difference in breast cancer surgery between the AWS group compared to the non AWS group was statistically significant (p=0.04). The portion of AWS in individuals who underwent bilateral mastectomy was high with all five participants experiencing AWS.

Figure 1:

Axillary web syndrome of the left axilla 5-years after surgery indicated by arrow.

Table 1:

Participant characteristics of the study cohort at 5-years post-surgery

Characteristic	AWS Group n=16 (57%)	Non-AWS Group n=12 (43%)	Total n=28 (100%)	P value
	n (%)	n (%)	# (%)
Breast Surgery				0.04a (χ2=6.435)
Lumpectomy	6 (38)	7(58)	13 (46)
Mastectomy	5 (31)	5 (42)	10 (35)
Contralateral prophylactic mastectomy	5 (31)	0 (0)	5 (18)
Axillary Lymph Node Surgery				0.32 (χ2=0.994)
Sentinel Node	11 (69)	11 (92)	22 (79)
Axillary Dissection	5 (31)	1 (8)	6 (21)
Radiation				0.97 (χ2=0.003)
Yes	8 (50)	7 (59)	15 (54)
No	8 (50)	5 (42)	13 (46)
Chemotherapy				0.96 (χ2=0.003)
Yes	8 (50)	5 (42)	13 (46)
No	8 (50)	7 (58)	15 (54)
Reconstruction				0.52 (χ2=0.411)
Yes	4 (25)	1 (8)	5 (18)
No	12 (75)	11 (92)	23 (82)
Age at diagnosis (years) $\overline{X}$ (SD) Range	61 (11) 42–79	66 (8) 46–78	63 42–79	0.26 (t=−1.2)
No. of LN removed $\overline{X}$ (SD) Range	7 (9) 1–32	3 (4) 1–14	5 1–32	0.10 (t=1.88)

Values are numbers (percentages) unless otherwise indicated. SNB=Sentinel node biopsy, ALND=Axillary lymph node dissection, $\overline{X}$ = mean, SD=Standard deviation, BMI=Body mass index, LN=Lymph node.

^aSignificance level: p≤0.05

Function and Pain

Function (Figure 2a): DASH scores were not significantly different between the AWS and non AWS groups collapsed across time (F=0.06, p=0.80). There was a significant main effect for time (F=13.94, p<0.0001) with total mean DASH scores across groups decreasing from 2-weeks to 78-weeks representing an improvement in function; however, at 5-years there was an increase in DASH scores representing more dysfunction. There was no significant interaction effect present (F=1.34, p=0.26).

Figure 2:

The 5-year temporal change of pain (a) and DASH scores (b) in the axillary web syndrome (AWS) group, Non-AWS group, and the total mean of both groups combined.

DASH=Disability of the Arm, Shoulder, and Hand; VAS=Visual Analog Scale, wk=week, Error bars=95% confidence interval

Pain (Figure 2b): There was no significant group effect (F=0.31, p=0.58) between the AWS and non AWS groups related to VAS pain scores. There was a significant change in pain over time (i.e. main effect for time) with pain decreasing from 2-weeks to 78-weeks; however, at 5-years there was an increase. There was no significant difference in VAS pain scores between the AWS and non AWS groups across time (i.e. no interaction effect) (F=1.62, p=0.17).

Range of Motion

Abduction PROM (Figure 3a): There was a time effect (F=19.17, p<0.0001) with abduction PROM increasing from 2-weeks to 12-weeks followed by a gradual decline through 5 years at 78 weeks and 5 years, respectively). There was a group effect (F=5.92, p=0.02) with the Non-AWS group having higher ROM (Mean=156°, SD=28) compared to the AWS group (Mean=139°, SD=30) collapsed across time. There was no interaction effect (F=2.01, p=0.10).

Figure 3:

The 5-year temporal change of shoulder range of motion in the axillary web syndrome (AWS) group and Non-AWS group and the total mean of both groups combined. a) abduction PROM, b) abduction AROM, c) flexion PROM, and d) flexion AROM

PROM=passive range of motion; AROM=active range of motion; Error bars=95% confidence interval, wk=week

*Groups were significantly different at the 2- and 4-week visits (p<0.05)

Abduction AROM (Figure 3b): There was an interaction effect (group × time) in shoulder abduction AROM (F=2.66, p=0.04) between the AWS group and Non-AWS group across time. Post hoc analysis determined the AWS group had significantly lower abduction AROM at 2-(AWS Mean=110°, SD=29 and Non-AWS Mean=135°, SD=31) and 4-weeks (AWS Mean=129°, SD=27 and Non-AWS Mean=151°, SD=25). Abduction AROM changed over time (i.e. time effect) collapsed across group (F=21.00, p=<0.001) with abduction AROM starting low at 2-weeks and increasing until 12-weeks followed by a decline at 78-weeks and 5-years. There was a group effect (F=5.45, p=0.03) with the Non-AWS group having significantly higher abduction AROM (Mean=150°, SD=23) compared to the AWS group (Mean=138°, SD=26) collapsed across time.

Flexion PROM (Figure 3c): A time effect (F=20.18, p<0.0001) was present demonstrating a gradual increase in flexion PROM across visits collapsed across group. There was no significant group effect (F=1.33, p=0.26) or interaction effect (F=1.14, p=0.34).

Flexion AROM (Figure 3d): There was change in flexion AROM over time (F=11.72, p<0.0001) with an inverse J-shaped curve reflecting a gradual increase in AROM until 78 weeks followed by a decrease at the 5-year visit collapsed across group. No significant group effect (F=2.72, p=0.11) or interaction effect was present (F=1.64, p=0.16).

Lymphedema Measures

Arm measurements (Table 2): There was no group effect between the AWS group and the non AWS group (F=28.29, p=0.28), time effect (F=1.73, p=0.15), or interaction effect (F=0.49, p=0.74) in L-Dex measures. Girth measures (volume difference in ml and percent volume difference, respectively) also did not demonstrate a group effect (F=0.02, p=0.90 and F<0.0001, p=0.95), time effect (F=0.30, p=0.88 and F=0.37, p=0.83), or interaction effect (F=0.27, p=0.89 and F=0.24, p=0.91).

Table 2:

Lymphedema measures in the axillary web syndrome (AWS) and Non-AWS group across 5-years.

Variable	AWS $\overline{X}$ (95% CI)					Non-AWS $\overline{X}$ (95% CI)
	Time					Time
	2 week	4 week	12 week	78 week	5 year	2 week	4 week	12 week	78 week	5 year
Upper extremity
Volume (%)	0.4 (−1.1, 2.0)	0.5 (−1.0, 2.0)	0.5 (−1.0, 2.1)	0.1 (−1.4, 1.6)	0.7 (−0.9, 2.4)	1.4 (−0.2, 3.0)	0.4 (−1.2, 2.0)	0.8 (−0.8, 2.4)	−0.2 (−2.0, 1.67	0.3 (−1.6,2.2)
Volume (mL)	9.6 (−22.3, 41.5)	8.2 (−23.7, 40.1)	9.5 (−22.4, 41.5)	1.0 (−30.9, 32.9)	18.9 (−15.9, 53.6)	32.2 (−1.5, 66.0)	9.1 (−24.7, 42.8)	16.6 (−17.2, 50.3)	4.0 (−34.6, 42.6)	4.7 (−35.5, 44.9)
BIS (L-Dex value)	2.0 (0.5, 3.4)	−0.1 (−1.5, 1.4)	0.0 (−1.5, 1.4)	0.6 (−0.8, 2.1)	0.2 (−1.4, 1.8)	0.7 (−0.8, 2.3)	−0.7 (−2.2, 0.9)	0.4 (−1.2, 2.0)	−0.8 (−2.5, 1.0)	−1.2 (−3.0, 0.7)
Trunk
TDC ratio	1.3 (1.2, 1.4)	1.2 (1.1, 1.3)	1.3 (1.2, 1.4)	1.1 (1.0, 1.2)	1.0 (0.9, 1.1)	1.3 (1.2, 1.5)	1.1 (1.0, 1.3)	1.3 (1.2, 1.4)	1.1 (1.0, 1.3)	1.1 (1.0, 1.2)

$\overline{X}$ =mean, CI=95% confidence interval, % = percent, mL =milliliters, TDC=tissue dielectric ratio

Trunk measurement (Table 2): There was a significant change in TDC measures over time (F=5.45, p<0.001) with TDC ratios decreasing from 2-weeks to 4-weeks with an increase at 12-weeks and a gradual decrease until 5-years. There was no group (F=0.07, p=0.79) or interaction effect (F=0.76, p=0.56).

Upper Extremity Physical Impairments and AWS as a Risk Factor

The point prevalence of any upper extremity physical impairment at each time point was 97%, 81%, 81%, 66%,¹⁵ and 75% at 2-, 4-, 12-, and 78-weeks, and 5-years, respectively. At 5-years, 50% of the women experienced reduced shoulder range of motion, 39% reduced function, 29% lymphedema, and 25% pain. Univariate logistic regression results for AWS as risk factors for physical impairments are presented in Table 3. AWS was identified as a risk factor for reduced shoulder abduction and flexion AROM 5 years after surgery.

Table 3:

Prevalence of upper extremity physical impairments and univariate analysis of axillary web syndrome as a risk factor for upper extremity physical impairment at 5-years.

Physical impairment	5-year cohort n (%)	Odds Ratio	95% CI		Wald Probability
			Lower	Upper
Reduced flexion AROM	6 (21)	7.22	0.71	72.7	0.09*
Reduced flexion PROM	3 (11)	2.17	0.17	27.07	0.55
Reduced abduction AROM	9 (32)	6.00	0.97	37.30	0.05*
Reduced abduction PROM	10 (36)	3.67	0.07	19.12	0.12
Reduced function	11 (39)	0.40	0.08	1.91	0.64
Pain	7 (25)	1.36	0.25	7.32	0.72
Arm Lymphedema	3 (11)	2.17	0.17	27.08	0.55
Trunk Lymph	7 (25)	0.68	0.12	3.83	0.66
Any impairment	21 (75)	1.33	0.22	8.22	0.76

AROM=active range of motion; PROM=passive range of motion

^*AWS associated as a risk factor (p<0.10)

Rehabilitation

Thirteen of the 28 women (46%) received a minimum of one rehabilitation session within 5 years after surgery with no significant difference in treatment received between groups (AWS n=9, Non AWS n=4, p=0.11). Ten of the 13 women received lymphedema treatment (AWS n=6, Non AWS n =4). Five women described receiving range of motion exercises (AWS n=5, Non AWS n=0). One woman (0 AWS: 1 Non AWS) received weight bearing activities for osteoporosis prevention.

DISCUSSION

The cumulative incidence of AWS increased post breast cancer surgery to 57% at 5 years. Lower shoulder range of motion was observed in the early postoperative time period in women with AWS. AWS was associated with an increased risk of reduced shoulder range of motion 5 years after breast cancer surgery. Cording was present in a high number of women 5-years post-surgery demonstrating the chronicity of AWS. Regardless of AWS, this study showed an increase in physical impairments over time with 75% of women having upper extremity physical impairment 5-years after surgery including reduced shoulder motion, reduced upper quadrant function, pain and/or lymphedema.

This longitudinal study completed multiple data points in the same cohort of breast cancer survivors over a 5-year period which is a strength to the study. To our knowledge, it is the first study that demonstrated that AWS can persist for up to 5-years after surgery and have a negative long term impact on survivorship. Like other studies, AWS most often developed in the early postoperative time period^13,14,16,41 but delayed onset also occurred as demonstrated by the increase in cumulative incidence over the 5-years. The chronic nature of this condition negatively impacts long- and short-term outcomes. AWS increased the risk of long-term reduced shoulder motion 5-years after surgery. The reduced shoulder motion in the early postoperative period in women with AWS has been previously reported in our publications and demonstrated in other studies.^13,14,41 Of clinical importance, the AWS group had lower abduction AROM (−8°, and −7° at 78 weeks and 5 years, respectively) that exceeded the minimal clinical important difference (MCID) of 5.0° AROM for shoulder abduction,⁴² although the difference was not statistically significant. Flexion was affected less suggesting AWS may impact shoulder abduction more than flexion long term. Unlike other studies, ^16,17 an association between AWS and lymphedema was not detected in our study.

Three quarters of the women experienced upper extremity physical impairments 5-years after surgery which is an increase from the 66% that was experienced at 78-weeks in this same cohort.¹⁵ The most common upper extremity impairments were reduced function and range of motion which demonstrated a similar trend over the 5-years. Both measures initially improved post-operatively, but later worsened over time. Of clinical note, at 5 years both groups had a 9° reduction in abduction AROM (which exceeds the MCID) and 7° reduction in flexion AROM. Limitation in shoulder range of motion is a known contributing factor to functional loss.^43,44 The pain outcome demonstrates a similar trend of initial improvement followed by a worsening in pain. The overall trend of worsening of symptoms is notable for revealing chronic and delayed issues that arise following breast cancer surgery, not only from AWS but other potential contributing factors such as surgery, radiotherapy, chemotherapy, and endocrine therapy.^2,45,46 A significant difference was not present when a logistic regression was run using these variables. The aging process may have also impacted worsening of symptoms.

Our results show similar results as other studies demonstrating the high prevalence of long term upper extremity morbidity in the breast cancer population.^34,47–50 Growing evidence for a long-term rehabilitation plan or surveillance programs in the cancer rehabilitation realm have been documented in the literature to abate upper extremity disability.^51–53 Unfortunately, few facilities have been able to implement a cancer rehabilitation surveillance program. A surveillance program may be more beneficial in individuals that experience AWS since AWS can persist for years, recur, and increase the risk of short and long term shoulder restrictions. Future research is warranted to implement cancer rehabilitation treatment to determine the impact it has on short- and long-term outcomes

Study Limitations

We recognize that there are limitations to our study. This study focused on upper extremity impairments and did not include other issues that arise following cancer treatment such as weakness, chronic fatigue, neuropathy, balance issues, and cardiotoxicity. Another limitation is the small sample size of the study, in part due to the participants who were lost to follow-up reducing the study’s power. The sample size a priori was estimated using DASH while secondary and multiple analyses on the other variables are less powered. Future studies with larger sample sizes would be beneficial. Another limitation is the uncontrolled treatment effect and the unknown reliability of AWS assessment. Study participants did not receive any standardized therapies, but they were not prohibited from seeking out therapeutic interventions. Very few women developed lymphedema in our study. During the early implementation of this study, women received lymphedema education 12-weeks after surgery. The provided lymphedema education and the participants knowing that the PI was a PT (and the data collector at each visit) may have prompted women to seek rehabilitation treatment. It is recognized that interventions may have potentially impacted the outcomes. The small sample size and potential treatment effect may be a reason why the clinical outcomes were not significantly different between groups. Although, more participants with AWS received rehabilitation treatment compared to those without AWS which may have positively impacted outcomes in the AWS group compared to the other group. Participants did not have baseline pain scores, levels of function, or lymphedema measures, which is another limitation of this study. This study showed that AWS can sometimes reoccur after what appears to be resolution of the cords. There is a possibility that women in the Non-AWS group may have experienced AWS between visits, but it was not detected. Finally, it is a limitation that the patient population in this study was from one clinic at an academic research center, which may not be reflective of the population as a whole. Data was collected by a single assessor at all timepoints which reduced measuring variability but may have also introduced potential bias. The single assessor was not blinded from knowing prior AWS status, measurements, and breast cancer treatment history although the assessment for AWS performed last to minimize measuring bias.

CONCLUSIONS

This study revealed the long-term natural history of AWS and demonstrated the chronicity of the condition and the negative impact it has on shoulder motion. Regardless of AWS, breast cancer survivors experienced a worsening of upper extremity impairments 5-years after surgery. These findings demonstrate the need for long-term surveillance and interventions, such as rehabilitation, that could potentially identify, treat and prevent long-term morbidity as a result of both AWS and breast cancer treatment.

Abbreviations:

AWS

axillary web syndrome

AROM

active range of motion

PROM

passive range of motion

DASH

Disabilities of Arm, Shoulder, and Hand

REDCAP

Research Electronic Data Capture

VAS

visual analog scale

BIS

bioimpedance spectroscopy

TDC

tissue dielectric constant