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ORIGINAL ARTICLES |
From Park Nicollet Institute (KKS, MJN, LS, MWL, TMT), Minneapolis, Minnesota; The Breast Center of United Hospital (CC), St. Paul, Minnesota; and the University of Minnesota Division of Surgical Oncology (TMT), Minneapolis, Minnesota.
Correspondence: Address correspondence and reprint requests to: Karen K. Swenson, RN, MS, AOCN, Park Nicollet Institute, 3800 Park Nicollet Blvd., Minneapolis, MN 55416; Fax: 952-993-5235; E-mail: swensk{at}parknicollet.com
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Methods: The study compared side effects and interference with daily life between 169 women who underwent an SLND and 78 who underwent an ALND for breast cancer. Patients rated symptom severity and interference with daily life caused by pain, numbness, limitation of arm range of motion (ROM), and arm swelling at 1, 6, and 12 months after surgery by using the Measure of Arm Symptom Survey. Repeated-measures and regression analyses for each time period were used to determine associations between symptoms and dissection type.
Results: At 1 month, SLND patients reported less pain, numbness, limitation in ROM, and seromas than ALND patients. At 6 months, SLND patients had less pain, numbness, and arm swelling, and at 12 months, SLND patients had less numbness, arm swelling, and limitation in ROM than ALND patients. At 1 month, pain, numbness, and limitation in ROM interfered significantly more with daily life for ALND patients. At 6 and 12 months, only numbness interfered more with daily life for ALND patients.
Conclusions: SLND was associated with fewer side effects than ALND at all time points.
Key Words: Breast cancer • Surgery • Axilla • Sentinel lymph node • Arm side effects
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Recently, a less invasive procedure, sentinel lymph node dissection (SLND), has been developed to stage the axilla for invasive breast cancer. This technique is performed by using a blue dye and a radioactive tracer injected into the breast tissue. These agents travel along the lymphatic channels to the first draining lymph node, called the sentinel lymph node (SLN). SLNs are removed during the surgical procedure, and the pathology results from these nodes have been found to be highly predictive of metastatic involvement in the axilla.27–34 As a result, SLND has become an acceptable alternative to ALND for patients with clinically negative lymph nodes.28,32 Potential side effects of SLND are likely to be less than with an ALND because there is less extensive surgery in the axilla. A single-institution study has shown a reduction in arm numbness, arm pain, arm mobility, and lymphedema after SLND as compared with ALND.13 However, this study was limited to node-negative patients, with only one assessment ranging from 4 to 28 months after surgery.13 Another recently published study compared side effects between patients having an SLND and ALND along with breast-conserving surgery and found that SLND patients had less arm swelling and fewer subjective arm complaints.14 A study measuring lymphedema after surgery found that the incidence of lymphedema was less after SLND than ALND (3% vs. 17%).15 In another study evaluating postsurgical sensations after SLND and ALND, patients experienced fewer sensations such as tenderness or burning after SLND than ALND; however, this was true only for patients having breast-conserving surgery.16
The purpose of this study was to further compare the side effects after SLND and ALND. The research questions were the following: (1) do women who have had an SLND report fewer side effects (pain, numbness, arm immobility, arm swelling, seroma formation, and infection) and experience less interference with daily life than women who have had an ALND? and (2) does this comparison of SLND and ALND depend on time since surgery?
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Study Design
The Protocol Review Committee and institutional review boards at both institutions approved this longitudinal study before patient enrollment. Consecutive patients with invasive breast cancer who were undergoing breast surgery and planned SLND were identified. SLNs were identified by using both a radioactive tracer (technetium-labeled sulfur colloid) and isosulfan blue dye. Frozen-section analysis was performed on the SLN; a routine level I/II ALND was performed if metastases were identified. ALNDs were also performed if an SLN was not identified or if the surgeon was in the process of SLND training. SLNs were evaluated for metastatic disease by using serial sectioning, routine hematoxylin and eosin (H&E) pathologic analysis, and immunohistochemical (IHC) analysis. If SLNs were negative on frozen section, but permanent sections later identified cancer cells by H& E or IHC staining, some patients chose to have an ALND. Nodes from the ALND were evaluated for metastatic disease with routine H&E pathologic analysis. After surgery, chemotherapy and breast irradiation therapy were administered sequentially if both were indicated. Axillary radiotherapy was not performed after either SLND or ALND.
Enrollment began in February 1999 and ended in November 2000. Potential participants were sent a letter inviting them to participate in the study. If they chose to complete the study, they were asked to sign and return the consent form along with their first questionnaire. Participants were eligible for the study if they had clinical stage 0 to II breast cancer, had a planned SLND or SLND plus ALND, and signed the consent form to participate. Patients were excluded from the study if they had prior chemotherapy for breast cancer, had multicentric breast cancer, had prior extensive breast or axillary surgery, or were unable to read or write English. Of the women undergoing breast cancer surgery during the enrollment period, 261 had a planned SLND. Surveys were mailed to these 261 women.
Questionnaire
The Measure of Arm Symptom Survey (MASS) was developed for this study because there were no instruments available to comprehensively assess arm symptoms. Some of the survey questions were taken and revised (with permission) from a previously developed instrument that measured arm symptoms after ALND.21 Face validity of the MASS was established by administering the questionnaires to a group of surgeons, oncology nurses, patients, and others with expertise in questionnaire design. Revisions were made accordingly. Reliability testing was not performed. The MASS was administered to all participants at 1, 6, and 12 months after surgery. Participants who did not return the questionnaire within 2 weeks were sent a reminder letter with another copy of the questionnaire.
The MASS assessed breast, chest, and axillary pain; numbness or tingling of the breast, chest, axilla, or arm; limitation of shoulder or arm range of motion (ROM); and arm or hand swelling. It addressed symptom severity by having participants rate each of their symptoms on a five-point scale from none to a very severe symptom. The degree of interference with life activities for each symptom was also rated with a similar five-point scale of "not at all" to "very much." Information on infections of the breast, chest, or arm since the time of surgery was also obtained, and participants were asked about antibiotic treatments. Participants were asked about seroma aspirations on the 1-month survey ("How many times has fluid from under your arm been removed with a needle since your surgery?"). They were also asked about the number of axillary drains and the length of time they were left in place. A question was included on the 1-month survey asking about the number of days lost from work because of breast cancer surgery or treatment.
Other factors assessed in the MASS included diabetes, cigarette smoking, past shoulder or arm injury, arm exercises after surgery, height, weight, and occupation. Chart review was conducted to determine the patient’s age at diagnosis and treatment factors, such as the number of lymph nodes removed, the number of positive lymph nodes, radiotherapy, chemotherapy, hormone therapy, mastectomy/breast-conserving surgery, reconstruction/no reconstruction, tumor size, and tumor location.
Data Analysis
With a two-tailed alpha level of .05 and a sample size of 261, the power to detect a difference of 20% between the proportion of women in the ALND group versus the SLND group who experienced a particular side effect was >.80 for all variables. The power to detect a difference of 15% between groups was >.80 for all variables except pain (power = .64), limitation in ROM (power = .59), and days lost from work (power = .72). Differences in the 15% to 20% range were considered clinically significant.
For comparisons of the SLND and ALND groups on the presence and severity of pain, numbness, limited ROM, and arm swelling, responses were categorized as none, mild, or moderate/severe/very severe. Responses to other survey questions were dichotomized as none versus some. Comparisons of the SLND and ALND groups used t-tests for continuous variables and 
2 tests (or Fisher’s exact test when necessary) for categorical variables.
The association between symptoms and type of dissection was further evaluated by using multiple regression methods for repeated measures (GENMOD procedure; SAS Institute, Inc., Cary, NC).35 For this purpose, responses to all survey questions were dichotomized (symptom present vs. absent, symptom interference with daily life present vs. absent). Analyses assessed associations of each outcome variable with the type of dissection and included the following variables as covariates: age (coded as a continuous variable), type of breast surgery (breast-conserving surgery vs. mastectomy with or without reconstruction), and chemotherapy (yes vs. no). All of these covariates were included because the ALND and SLND groups differed on these variables. Body mass index (BMI; coded continuously) was also included as a covariate and was calculated for each woman by dividing the weight (kg) by the height (m2).
Regression analyses were also performed on data from each time period (1, 6, and 12 months) individually. These analyses assessed associations of each outcome with type of dissection, both with and without adjustment for the covariates used in the repeated-measures analysis. The pattern of results was unaffected by the inclusion of these covariates, except where noted otherwise in Results. All tests were two tailed and were considered statistically significant at P < .05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patient Characteristics
The characteristics of the 247 patients enrolled in this study are listed in Table 1. The mean age of the sample was 57 years (median, 56 years), with a range from 28 to 87 years. Most patients were white (96%), whereas 2% were Asian, 1% were black, and 1% were Hispanic. The mean tumor size for the overall sample was 1.7 cm. The mean number of nodes removed was 2.0 for the SLND group and 16.1 for the ALND group. Thirty-five percent of participants (n = 86) had node-positive cancer by either H&E or IHC analysis. Of the 67 participants who had a positive SLN on the H&E analysis, 53 (79.1%) went on to have an ALND. However, of the 18 participants who had a positive SLN on only the IHC analysis, only 3 participants (16.7%) went on to have an ALND. An ALND was performed for 11 patients (4%) for whom a SLN was not identified and for an additional 11 patients (4%) when the surgeon was in the process of SLND training or for other reasons. Twenty-one surgeons participated in the study, with each surgeon performing a mean of 12 cases in this study.
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Repeated-measures analyses also indicated that all symptoms except swelling, interference with daily life from swelling, and interference with daily life from infection decreased over time (all P values <.05). Because the prevalence of symptoms depends on the time period, results comparing SLND and ALND at 1, 6, and 12 months are analyzed separately and reported in Tables 3 through 5 and graphically presented in Fig. 1.
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Six-Month Results
At 6 months after surgery, SLND patients continued to report significantly less pain and numbness than ALND patients (Fig. 1). The proportion of patients reporting symptoms (mild/moderate/severe/very severe) among SLND versus ALND patients was 37.4% vs. 57.5% for pain and 30.3% vs. 83.1% for numbness (Table 4). At 6 months, SLND patients were significantly less likely to report arm swelling than ALND patients (4.7% vs. 19.5%). No differences were reported between the groups in limitations in ROM or infection rates at 6 months after surgery.
Twelve-Month Results
At 12 months after surgery, SLND patients reported less numbness, limitation in ROM, and arm swelling than ALND patients did (Fig. 1). SLND patients also reported less pain at 12 months, but when adjusted for chemotherapy, nodal status, stage, and all covariates, the groups did not differ significantly. The proportion of patients reporting symptoms (mild/moderate/severe/very severe) among SLND versus ALND patients was 28.7% vs. 46.8% for pain, 24.9% vs. 81.2% for numbness, 6.4% vs. 20.7% for limitation in ROM, and 3.5% vs. 14.3% for arm swelling (Table 5). Rates of infection did not differ between the two groups at 12 months after surgery.
Interference With Daily Life
At 1 month after surgery, pain, numbness, and limitation in ROM interfered more with daily life for patients who had an ALND than for those who had an SLND (Table 3). At 6 and 12 months after surgery, there were no differences between the groups in the proportion of patients reporting interference with daily life from pain or limitations in ROM (Tables 4 and 5). Only numbness continued to interfere more with daily life for ALND patients than SLND patients at 6 and 12 months after surgery. There were no differences in interference with daily life related to arm swelling or infection at any of the time points. Of the patients who were employed at the time of diagnosis, fewer SLND than ALND patients lost more than a week from work because of their surgery and treatment for breast cancer (62.8% vs. 85.4%), although this factor was no longer significant when adjusted for chemotherapy, nodal status, stage, or all covariates.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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2 years after ALND, patients rated arm symptoms such as pain, limitations in ROM, and swelling as their most distressing problem after breast cancer treatment.36 Our study corroborates previous work by Schrenk et al.13 that patients experience less pain, numbness, and ROM restrictions after SLND than ALND. Although these symptoms decreased over time for both groups, ALND patients experienced significantly more side effects at all three time points. Although the rate of arm swelling was not different between the groups at 1 month after surgery, it was significantly greater at 6 and 12 months for the ALND patients than SLND patients. The patient-reported rate of lymphedema for SLND patients in our study at 12 months was similar to the measured rate in a previous study (3.5% vs. 3%, respectively), as were the lymphedema rates for ALND patients (14.3% vs. 17%, respectively).15 The incidence of infection in the axilla, arm, breast, or chest wall was not significantly different between the two procedures. Although there is less disruption to the axilla with SLND, there may be a slightly longer time in surgery with SLND. This question about infections may also have been confusing because participants were asked to report the incidence of infection "since your surgery," and this was the only cumulative question on the survey.
It seems that SLND decreases the degree of interference with daily life caused by arm symptoms. At 1 month after surgery, ALND patients reported more interference with daily life from pain, numbness, and limitation in ROM than SLND patients. ALND patients also lost more days from work, although this is likely related to the greater proportion of patients receiving chemotherapy after ALND. Numbness continued to present more of an interference with daily life for ALND patients at 6 and 12 months after surgery. ALND patients were more likely than SLND patients to have numbness/tingling either in the axilla or radiating down the arm (data not shown). It is interesting to note that although lymphedema is often thought to present the biggest problem after breast surgery, we found that pain, numbness, and limitation in ROM were causing more interference with daily life at all three time points for both groups. This may be because lymphedema is more likely to be a late effect that may present more difficulty later on after surgery.
A limitation to this study is that some of the patient and disease characteristics, such as patient age, tumor size, and nodal status, differed between the two groups. Adjuvant chemotherapy was much more common in the ALND group because of positive nodal status. These factors may affect some of the postoperative side effects. However, most of the symptoms measured in this study are more likely to be related to the surgery than to other factors. Results were analyzed adjusting for the type of breast surgery, age, chemotherapy, nodal status, tumor size, and stage of disease, and the pattern of results was unaffected, except where noted, by the inclusion of these covariates. Another limitation is that reliability testing was not performed with the instrument. However, the lymphedema rates found in this study were very similar to the rates found in a recently published study,15 and other studies have reported comparable side effects of ALND and SLND by using a variety of other instruments.13–16 Finally, participants for this study were from one geographic area of the country and were primarily white women.
Nevertheless, to the best of our knowledge, this is the first prospective, multi-institutional study comparing side effects between the two procedures over time. It includes patients with both positive and negative nodes. This study also evaluates side effects at multiple, defined time points of 1, 6, and 12 months after surgery. Finally, the study relied on patient self-report for all measures. Patient report is the most appropriate source for symptoms such as pain and numbness, and it is a reliable source of whether patients are experiencing arm swelling.13,20,23 Patient report is also the only source for assessing the effect of these symptoms on daily activities.
In conclusion, side effects after axillary surgery can have a significant effect on patients’ lives. This study found that SLND side effects were significantly less than ALND side effects up to 12 months after breast cancer surgery. Future research is required to look at long-term side effects. However, considering the favorable short-term side-effect profile and superior staging accuracy with SLND,33–34 this procedure offers an improvement for breast cancer surgical treatment.
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Acknowledgments |
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Footnotes |
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Received for publication February 11, 2002. Accepted for publication May 14, 2002.
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REFERENCES |
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