Abstract
Background Axillary web syndrome (AWS) is a condition that may develop following breast cancer surgery and that presents as a palpable axillary cord of tissue.
Objective The purposes of this study were: (1) to determine the clinical characteristics of AWS related to movement, function, pain, and postoperative edema and (2) to define the incidence of and risk factors for AWS within the first 3 months following breast cancer surgery.
Design This was a prospective cohort study with a repeated-measures design.
Methods Women who underwent breast cancer surgery with sentinel node biopsy or axillary lymph node dissection (N=36) were assessed for AWS, shoulder range of motion, function, pain, and postoperative edema (using girth measurements, bioimpedance, and tissue dielectric constant) at 2, 4, and 12 weeks. Demographic characteristics were used for risk analysis.
Results Seventeen women (47.2%) developed AWS, and AWS persisted in 10 participants (27.8%) at 12 weeks. Abduction range of motion was significantly lower in the AWS group compared with the non-AWS group at 2 and 4 weeks. There were no differences between groups in measurements of function, pain, or edema at any time point. Trunk edema measured by dielectric constant was present in both groups, with an incidence of 55%. Multivariate analysis determined lower body mass index as being significantly associated with AWS (odds ratio=0.86; 95% confidence interval=0.74, 1.00).
Limitations Limitations included a short follow-up time and a small sample size.
Conclusion Axillary web syndrome is prevalent following breast/axilla surgery for early-stage breast cancer and may persist beyond 12 weeks. The early consequences include movement restriction, but the long-term effects of persistent AWS cords are yet unknown. Low body mass index is considered a risk factor for AWS.
Breast cancer surgery with axillary lymph node dissection (ALND) or sentinel node biopsy (SNB) is considered standard treatment for management of early-stage breast cancer.1 Breast cancer surgery can result in short-term and long-term complications such as infection, arm weakness, motion restriction, pain, functional loss, lymphedema, and axillary web syndrome (AWS).2–12
Axillary web syndrome, also known as cording, is an often overlooked problem that has been reported to cause morbidity in the early postoperative period10,11 and could be an initiating factor for some of the postsurgical breast cancer complications, such as movement restriction, pain, functional loss, and lymphedema. The incidence of AWS has been poorly defined, with widely differing incidence rates ranging from 6% to 72% following breast cancer surgery.9,12,13 On physical examination, AWS has been characterized as a tight cord that is present in the underlying superficial tissue of the axilla, arm, or chest wall that causes pain and limits upper extremity movement.9–12 Figure 1 depicts a visible cord associated with AWS. The cord frequently develops within weeks following surgery and has been proposed to resolve spontaneously by 3 months.10,11 Some investigators have suggested these cords may not completely resolve and lead to long-term restriction of movement of the shoulder and upper extremity.12,13
A visible cord associated with axillary web syndrome of the right axilla indicated by arrow.
Movement restrictions, functional loss, pain, and lymphedema are established chronic morbidities following surgical management in woman with breast cancer10,14–16 and have been identified in patients with AWS.12 It is possible that early postoperative movement restrictions, functional deficits, pain, and edema may be associated with AWS development. Because AWS is considered a risk factor for lymphedema development,17 determining the clinical characteristics unique to AWS would identify associations with established chronic morbidities and could lead to early identification and preventive or rehabilitation interventions.
The purposes of this study were: (1) to determine the clinical characteristics and natural history of AWS related to movement, function, pain, and edema measures and (2) to define the incidence of and risk factors for AWS within the first 12 weeks following breast cancer surgery. We hypothesized that participants with early onset of AWS would have persistent signs of AWS at 12 weeks, as well as greater movement restrictions, functional deficits, pain levels, and edema measures, compared with participants without AWS.
Method
Design
This was a prospective cohort study with a repeated-measures design. Based on previous literature with clinically meaningful differences in Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores of 20 and an effect size of 1.3, a power of 0.95 was determined a priori, with a .05 significance level and a total of 36 participants. A 2:1 allocation ratio (24 participants without AWS:12 participants with AWS) was anticipated based on past incidence rates, and power calculations were performed using the G*Power version 3.1 (Kiel University, Kiel, Germany). The estimated total sample sizes for all other outcome measures were n=20 for shoulder range of motion (ROM), n=10 for pain, n=24 for bioimpedance spectroscopy (BIS), and n=26 for tissue dielectric constant (TDC) to achieve a power of 0.80 with a .05 significance level using estimated effect sizes and assuming a 2:1 allocation ratio. Girth measurement sample size was not calculated a priori. A total of 36 women undergoing breast cancer surgery were recruited from the University of Minnesota by the primary investigator (L.A.K.). Participants were recruited at the preoperative or first postoperative surgical visit and screened for eligibility. Written informed consent was obtained at the first postoperative visit.
Participants
Eligible participants included women who underwent surgical treatment (lumpectomy or mastectomy) for early-stage breast cancer, including a minimum removal of one axillary lymph node by SNB. Contralateral prophylactic mastectomy (CPM) was allowed. Participants were excluded if they had undergone previous surgical treatment for breast cancer, surgery of either the axilla or shoulder, synchronous bilateral breast cancer, a previous history of shoulder dysfunction in either shoulder, or a history of upper extremity deep vein thrombosis.
AWS Diagnostic Assessment
The women were assessed for AWS at each study visit (2, 4, and 12 weeks postoperatively) by the principal investigator, a physical therapist and certified lymphedema therapist with more than 15 years of clinical experience. Participants were defined as having AWS when a palpable or visible cord of tissue was present in the axilla, upper extremity, or trunk during maximal shoulder abduction at any data collection time point within 12 weeks following surgery. Such cords did not have to be associated with local pain or restriction of shoulder ROM. Women who became aware of a cord by self-examination between visits were asked to schedule an immediate study visit to permit performance of an additional assessment. All clinical outcome variables were measured prior to AWS assessment to reduce bias in measures.
Demographic Characteristics and Clinical Outcome Measures
Data for demographic characteristics were collected by self-report and validated by review of medical records. Function, pain, ROM, and edema assessment were measured with validated tools at each study visit.
Measurements of shoulder abduction active range of motion (AROM) were made bilaterally in the standing position using a standard goniometer method.18 Shoulder abduction passive range of motion (PROM) measurements were taken bilaterally in the supine position.18
The DASH questionnaire was used to measure function, and a visual analog scale (VAS) was used to provide a subjective pain assessment of any new pain that developed after surgery. The DASH tool is a self-report questionnaire that measures functional activities of the whole arm in people with musculoskeletal disorders and has been recommended for use in patients with breast cancer.19–21 DASH scores range from 0 to 100, with 0 reflecting no disability and a higher score indicating increased disability. The VAS has been reported to provide quantifiable, reliable (r=.97) measurements of pain ranging from 0 to 100.22
The edema assessment included performance of upper extremity girth, BIS, and TDC measurements. Above-normal edema measurements in this study were not considered a diagnosis of lymphedema because abnormal measurements at this early time period could be postoperative edema. Girth circumference was measured first, followed by BIS and TDC. A nonstretch, flexible tape measure with a tension gauge was used to acquire the girth measurements. Girth measurements were obtained bilaterally at 8-cm increments from the distal portion of the ulnar styloid to the axilla in the supine position. Girth measurements were used to calculate volume (V) for each upper extremity using the truncated cone formula: V=h/12π(C12+C1C2+C22), where h is height and C is circumference.23 The volume difference between the extremities was calculated as a percent volume difference.
Bioimpedance spectroscopy (Dex U400, ImpediMed, San Diego, California) was used to measure upper extremity edema at each visit. Bioimpedance spectroscopy measures the tissue resistance to an electrical current to determine the extracellular fluid volume, which includes lymph fluid.24 The BIS technique has been previously described,24,25 and measurements are expressed as a lymphedema index (L-Dex) score, with normal values ranging from −10 to 10.
Local tissue water measurements of the trunk were taken using Delfin Technologies MoistureMeterD (Delfin Technologies, Kuopio, Finland). Tissue dielectric constant is based on tissue electric properties and is dependent on the amount of water in the tissue, which affects the value of the TDC.26–29 The value increases with the increase of water in the tissue. A cylindrical probe is placed on a localized area of the body and a high-frequency (300 MHz), low-power electromagnetic wave is emitted into the tissue. The reflected electromagnetic wave displays as a number related to the amount of water in the tissue.26,27 The display value ranges from 1 to 80, with pure water having a value of about 78.5 and air having a value of about 1.26 Comparing values in people with lymphedema, a TDC ratio is calculated by dividing the affected lymphedema side by the unaffected side.27,29 A proposed TDC ratio of 1.2 or higher is suggested as an above-normal measure indicative of edema.27,29
Trunk edema was assessed by taking local tissue water measurements on the lateral chest wall 8 cm below the axillary fold bilaterally in the supine position. Upper extremity edema was defined when: (1) the circumferential volume difference was more than 10% greater between the affected and unaffected arms,30 (2) the BIS L-Dex value was >10 or showed an increase of >5 over time, or (3) the TDC ratio was >1.2.29,31
Data Analysis
Clinical characteristics (shoulder abduction, function, pain, and edema) were analyzed with repeated-measures analysis of variance (group and time as factors) using a .05 significance level. A participant identified with AWS at any time point was consistently allocated to the AWS group for final analysis across all time points. The Mauchly test statistic32 was used to check for circularity, a test for homogeneity of variance. If the Mauchly criterion was violated, the statistical program automatically corrected the P value using the Geisser-Greenhouse correction.32 This correction reduced the chance of a type I error. A Tukey-Kramer adjustment was performed for visit effect per group and group effect per visit if an interaction effect was identified. Descriptive analysis described cord presence at 12 weeks. A priori and with statistical consultation, the statistical plan was to analyze participant characteristics as risk factors using logistic regression with a more lenient P value of .10 if there was less than 20% loss to follow-up. The rationale for this higher P value was to not exclude a potentially important variable because the study sample size was low. A univariable logistic regression was used to determine possible risk factors for AWS. For ease of interpretation, age data were divided by 10 so the data could be interpreted as every 10-year change in age if deemed a risk factor for AWS. A multivariable logistic regression was then applied to analyze the statistically significant variables from the univariable analysis to control for possible confounding variables between AWS and the factors that showed statistical significance using a P value of .10. Analysis was performed using NCSS statistical program version 9.0 (NCSS, Kaysville, Utah).
Role of the Funding Source
This project was supported, in part, by the University of Minnesota Foundation, the Doctoral Dissertation Fellowship, and NIH P30 CA77598 utilizing the Masonic Cancer Center and University of Minnesota shared resources.
Results
Thirty-six women who underwent surgical treatment for breast cancer fulfilled eligibility criteria and consented to study participation. There was 100% adherence for all study visits (Fig. 2). Demographic characteristics of the study cohort are presented in Table 1. Seventeen of 36 women (47.2%) developed AWS within 12 weeks following surgery. One participant, initially presenting with AWS in the axilla, received an extra AWS assessment after developing an additional cord on her trunk. The prevalence of AWS was 41% in participants with SNB and 71% in those with ALND. Six out of 7 women (85.7%) undergoing CPM developed AWS. Ten women (27.8%) continued to demonstrate signs of AWS at the 12-week postoperative visit. Of these participants, 8 had cords present at all 3 visits, and 2 presented new evidence of cords at 12 weeks. Figure 1 shows a woman with persistent AWS at 12 weeks. Participants followed the institution's normal practice patterns regarding provision of rehabilitation for upper extremity physical impairments. Four participants (2 with AWS, 2 without AWS) underwent rehabilitation within 12 weeks after surgery, which may have included treatment for AWS, ROM deficits, lymphedema, functional loss, or pain.
Flowchart of study participants. AWS=axillary web syndrome.
Demographic Characteristics With Univariate Analysis of the Study Cohorta
Clinical Measures
Shoulder abduction.
There was an interaction effect (Fig. 3) between groups over time related to shoulder abduction AROM (F=4.23, P=.02) and PROM (F=3.16, P<.05). Shoulder abduction AROM and PROM were statistically lower in the AWS group compared with the non-AWS group at 2 weeks and 4 weeks but not at 12 weeks (P<.05). The AWS group had a significant increase in PROM and AROM at each visit (P<.05). The non-AWS group had a significant increase in shoulder abduction PROM and AROM from 2 to 12 weeks (P<.05). Neither group achieved full ROM by 12 weeks in comparison with the contralateral side.
Shoulder abduction passive range of motion (PROM) and active range of motion (AROM). ROM=range of motion, AWS=axillary web syndrome. Error bars=95% confidence intervals of the mean data. *Significant interaction effect across time. †Groups were significantly different at the 2- and 4-week visits (P<.05).
DASH and VAS pain scores.
Results for the DASH and VAS pain evaluation are presented in Table 2. There was no interaction or statistical group difference in mean DASH scores (F<0.01, P>.99) between the AWS group (X̅=17.9, standard error [SE]=3.8) and the non-AWS group (X̅=17.9, SE=3.7) collapsed across time points. There was a significant decrease in DASH scores over time (F=23.39, P<.001). There was no statistical significance in the “pain with movement” VAS scores between the AWS group (X̅=24.7, SE=4.0) and the non-AWS group (X̅=23.4, SE=3.9) collapsed across time points (F=0.05, P=.82). Pain with movement significantly decreased in both groups over time (F=8.11, P<.001).
DASH, Pain, and Edema Measuresa
Edema measurements.
Localized edema measurements for the trunk using TDC are displayed in Table 2. There were no significant group differences in trunk TDC ratios (F=0.01, P=.91) between the AWS group and the non-AWS group. Overall, 20 participants (11 with AWS, 9 without AWS) demonstrated trunk edema at 12 weeks with a TDC ratio >1.2.
Table 2 displays the results for upper limb edema measures, showing changes in extracellular fluid using bioimpedance and percent volume difference. There were no significant differences in bioimpedance L-Dex values (F=0.11, P=.74) collapsed across time points between the AWS group (X̅=0.13, SE=1.1) and the non-AWS group (X̅=0.65, SE=1.1). There was a time effect on BIS collapsed across groups (F=4.98, P=.01), with values decreasing from 2 to 4 weeks and increasing from 4 to 12 weeks in both groups. There were no significant differences between groups in upper extremity edema using girth circumference measurements (F=1.1, P=.30) collapsed across time points. Only one woman was identified with upper extremity edema using BIS and girth circumference measurements, indicating possible early upper limb lymphedema. One woman was unable to transfer out of the wheelchair because of a decline in health; therefore, bioimpedance was unable to be measured at the final visit and was missing from the full analysis.
Risk factors for AWS.
Univariate analysis for association of AWS with demographic characteristics is presented in Table 1. Younger age (P=.09), lower body mass index (BMI) (P=.05), a higher number of resected lymph nodes (P=.09), and CPM (P=.06) were associated with an increased risk of developing AWS. In subsequent multivariate analysis (Tab. 3), only the baseline BMI was determined to be a significant risk factor (P=.09). For every 1-kg/m2 increase in BMI, the odds of developing AWS decreased by a factor of 0.86.
Multivariate Analysis of the Study Cohorta
Discussion
Early ROM shoulder restrictions are evident in people with AWS. Many of the women following breast cancer surgery did not achieve full pain-free, functional ROM by 12 weeks with or without an AWS diagnosis. Resolution of AWS by 12 weeks did not occur in all women, which raises questions about the possible long-term effects of nonresolution of the AWS cords. A high incidence of AWS was observed within the first 12 weeks following breast cancer surgery. Lower BMI, younger age, increased number of lymph nodes removed, and CPM were identified as risk factors for AWS, with lower BMI being the best predictor. Trunk edema was observed using the quantifiable TDC technique in more than half the participants, indicating trunk edema.
Shoulder abduction ROM was significantly lower in the AWS group in the early postoperative period, which is consistent with the literature.9–11 Movement deficits persisted at 12 weeks in our study, which contradicted a previous study that showed full range of shoulder abduction with the exception of one participant (3%).10 A treatment effect may explain the improvement in ROM in previous studies. Our observational study followed the normal practice patterns, which entailed a total of only 4 participants (2 in each group) receiving rehabilitation for an upper extremity dysfunction. We could not control for a possible treatment effect if such an effect existed; however, we believe any effect was minimal because few individuals received treatment and the number was equal in both groups. Despite a statistically significant reduction in pain and improved function over time and regardless of AWS, neither group achieved pain-free motion by 12 weeks. Also, the magnitude of change observed in pain and DASH scores was less than the minimal clinically important difference.33,34 Therefore, it is questionable if the change is clinically relevant. Our study revealed physical deficits were present at 12 weeks following surgery regardless of the change over time and despite having AWS. This finding suggests that people may benefit from earlier rehabilitation intervention, as early intervention programs for upper extremity motion impairments have demonstrated significant improvements.35,36
To our knowledge, this is the first study to objectively measure edema using both BIS and TDC techniques in women with AWS. As expected, a difference in edema measures at this relatively early time point could not be detected because lymphedema most often develops beyond 12 weeks.30,37 Women who underwent a CPM were included, which may have further obscured the results, as additional surgery may have influenced measures. Using TDC, trunk edema was identified in 20 (55.6%) of the 36 participants. Arm edema was identified in only 1 woman using BIS and circumferential measures. These findings demonstrate a higher prevalence of trunk edema compared with arm edema postoperatively, although using different techniques to measure the trunk may have influenced these results. Because of the short follow-up of 12 weeks, we could not identify an association between postoperative edema and lymphedema development, which is a limitation of the study. A previous study demonstrated early postoperative arm edema significantly increases the risk for the development of arm lymphedema.37 These findings warrant future studies investigating postsurgical trunk edema and later development of trunk lymphedema.
The nonresolution of the cords in this study may carry implications regarding the possible long-term effects of persistent AWS cords. We suggest that chronic cording may lead to movement restrictions, altered movement patterns, poor posture, possible lymphedema, and other chronic issues, but a longer follow-up and a larger sample size would be needed in determining the long-term consequences of AWS. Our finding that AWS cords do not spontaneously resolve by 12 weeks differs from the previous literature.10,11 Ten of 17 women with AWS had cords at 12 weeks compared with the previously described resolution of cords in almost all women within the same time period.10,11 A treatment effect may explain the resolution of cords in previous studies. Yet, the relative benefit of treatment for AWS with nonsteroidal anti-inflammatory medications,38 physical therapy, manual techniques, exercises,9,11,12 and manual lymph drainage is not known.9
The overall AWS incidence of 47.2% in this study is higher than was observed in several previous reports.10,11,17,38 This difference may be due to the focused prospective design of this trial, in which each participant was followed closely for 12 weeks. A retrospective study indicated a much lower incidence of 6%.11 Another study showed an incidence of 28.1%, but only the women were followed for only 2 visits (1 and 45 days after surgery),38 which is outside the time period within which AWS often develops.11 A study that utilized patient self-report revealed a 16.2% incidence at 3 months and a cumulative incidence of 36.2% at 24 months.17 Our incidence of 41% was much higher in participants with SNB in contrast to a previous study reporting 20% but was comparable in women with ALND (71% versus 72%, respectively).10 To our knowledge, this is the first study to examine AWS in women with CPM, indicating a high incidence of 86%. We believe the incidence rate established in our prospective study may provide a more accurate assessment due to our efforts to establish a high enrollment rate from our recruitment, the ability to achieve 100% adherence with visits, and the frequency of our use of an objective AWS assessment following surgery. This approach would be anticipated to provide higher detection rates, as opposed to self-report. Similar to previous studies,9–11 the majority of women (88%) developed AWS within the first month, and fewer (12%) had a later onset. Participants in our study may have developed AWS beyond 12 weeks; therefore, the ongoing incidence may be even higher.
Consistent with the literature, younger age, lower BMI, and higher number of lymph nodes removed have been associated with AWS.10,11,17,38 Being the first AWS study to report on CPM, we also determined CPM as a risk factor for AWS. Contralateral prophylactic mastectomy involves a more invasive surgery; therefore, it is possible the further trauma to the system may increase the risk of AWS. The association of AWS with age may be explained by the fact that women tend to gain weight as they get older, and younger women may have more lymph nodes removed because they are more likely to have invasive breast cancer.24 Clinicians and women considering CPM should be aware of the possible risks of AWS development. In our study, multivariate analysis determined BMI was the best predictor of AWS. The relationship between AWS development and BMI remains unclear, but it has been suggested that the cords may not be visible because they are covered by adipose tissue, or it is possible that AWS cords are incapable of adhering to fatty tissue.10 The high prevalence of AWS emphasizes the need for clinicians to increase awareness of AWS, especially in those with lower BMI. This was a single-institution study within a single practice site, which may limit the generalizability of the results. Also, the reader should be cautioned that a higher P value of .1 was used to determine significant odds ratios.
Women with breast cancer surgery may benefit from a proactive assessment for AWS, as AWS is a prevalent condition associated with movement restriction of the shoulder in the early postoperative period. Axillary web syndrome cords do not universally resolve in all women by 12 weeks, which may lead to long-term physical complications. Lower BMI increases the risk of AWS development. There was a trend toward higher trunk edema measures in participants with AWS, but the relationship between AWS and lymphedema development remains unknown. Understanding this relationship is essential in determining the appropriate treatment for AWS. Trunk edema is measurable using TDC and more prevalent than arm edema within the first 12 weeks after surgery. This study indicates shoulder restriction, functional impairments, pain, and edema are apparent in patients with breast cancer, supporting the need for rehabilitation.
The results of this study suggest the need for future research regarding the long-term consequences of AWS and persistent cording using larger sample sizes, frequent assessment, and longer follow-up (the predominant limiting factors in this study) to determine the impact of AWS-associated movement restriction, pain, functional loss, and lymphedema. An intervention trial would be beneficial in determining the treatment effect of current rehabilitative interventions on AWS cord resolution. Further investigation of the etiology and pathophysiology of AWS also is warranted. The TDC results provide evidence of trunk edema in participants following breast cancer surgery, justifying further investigation of the use of TDC to determine the incidence of trunk edema or lymphedema.
Footnotes
Dr Koehler, Dr Blaes, Dr Haddad, Dr Hirsch, and Dr Ludewig provided concept/idea/research design. Dr Koehler, Dr Blaes, Dr Haddad, Dr Hunter, and Dr Hirsch provided writing. Dr Koehler provided data collection. Dr Koehler, Dr Blaes, Dr Haddad, and Dr Ludewig provided data analysis and fund procurement. Dr Koehler and Dr Haddad provided project management. Dr Koehler, Dr Haddad, and Dr Ludewig provided study participants and facilities/equipment. Dr Blaes and Dr Ludewig provided institutional liaisons. Dr Blaes, Dr Haddad, Dr Hunter, Dr Hirsch, and Dr Ludewig provided consultation (including review of manuscript before submission). The authors acknowledge Ryan Shanley for his statistical contribution and Fairview Health Services, and they give a very special thanks to all of the patients who generously participated in the study.
This prospective cohort study with repeated-measures design was approved by the University of Minnesota Institutional Review Board.
This project was supported, in part, by the University of Minnesota Foundation, the Doctoral Dissertation Fellowship, and NIH P30 CA77598 utilizing the Masonic Cancer Center and University of Minnesota shared resources.
- Received August 28, 2014.
- Accepted May 1, 2015.
- © 2015 American Physical Therapy Association
References
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