Axillary lymph node dissection (ALND) in breast cancer patients still represents the
routine surgical method for axillary staging. Although the axillary node status is
the most important prognostic factor for recurrence and survival (Fisher et al, 1984;
Carter et al, 1989) and information obtained by axillary dissection is useful for
planning adjuvant treatment, it is associated with substantial morbidity (Kissin et
al, 1986; Ivens et al, 1992; Keramopoulos et al, 1993; Hack et al, 1999; Kakuda et
al, 1999) and psychological distress (Maunsell et al, 1993; Tobin et al, 1993; Shimozuma
et al, 1999). Hack et al, showed arm/shoulder pain, weakness or numbness in 72% and
impaired range of motion in 73% of breast cancer patients after ALND, whereas high
levels of quality of life (QOL) were reported. Moderate to severe pain was reported
between 20, 23 and 32% (Van Dam et al, 1993; Kuehn et al, 2000; Ververs et al, 2001)
and was not significantly related to time since surgery. Other reports suggest that
arm problems after ALND are associated with a negative effect on the overall QOL of
breast cancer patients (Maunsell et al, 1993; Kuehn et al, 2000). As a result of the
need to reduce axillary morbidity, many investigations have been performed on sentinel
lymph node biopsy (SLNB), an alternative procedure. Using vital dye and/or radiocolloid,
the sentinel node/s as the first lymph node to receive lymphatic drainage from the
primary tumour can be identified by a minimal invasive surgical technique. Recently,
published data showed no sensory morbidity after SLNB (Giuliano et al, 2000) at a
median follow-up of 39 months. Schrenk et al (2000) reported less postoperative arm
pain, numbness and arm motion restriction after SLNB at a follow-up period of 15.4
months. The evaluation of morbidity after ALND vs SLNB is under investigation in ongoing
randomised trials as the NSABP B-32 and the ALMANAC trial. The evaluation of QOL issues
such as treatment side effects, patients satisfaction and symptom management are substantial
parameters in decision making regarding surgical interventions. However, at this time
little is known about the impact of SLNB on QOL in breast cancer patients.
The major objectives of this study are (1) to evaluate QOL differences in a short-term
follow-up after two surgical procedures (ALND and SLNB) in breast cancer patients
receiving breast-conserving treatment; (2) to determine the impact of SLNB on global
QOL of breast cancer patients and (3) to compare morbidity end points (arm/shoulder
mobility, pain, sensory morbidity) during different clinical phases.
MATERIALS AND METHODS
Selection of patients
In a prospective, longitudinal study between September 2000 and March 2002, we included
56 consecutive patients with newly diagnosed primary breast cancer. Study eligibility
criteria included the following: (1) breast cancer stage I or II, (2) breast-conserving
surgery in all patients, (3) patients' age between 18 and 80 years, (4) no severe
physical and mental comorbidity, (5) performance status 0 and (6) informed consent.
Procedures
A total of 56 patients with invasive breast cancer received the sentinel node biopsy.
In all, 25 patients receiving the SLNB only (Group I) were compared with 31 patients
who underwent the standard level I and II ALND (Group II) when intraoperative frozen
section showed metastatic disease. Before the study was started, a surgical protocol
was implemented in order to minimise differences in technique. Similar incisions,
similar anatomic dissections and similar drainage catheters were used. All patients
received breast-conserving surgery. Our technique of SLNB has been described previously
(Reitsamer et al, 2002). Briefly, SLNB was performed by the combined method using
peritumoral injection of technetium-99m-labelled albumin (Nanocoll®, Sorin Biomedica,
Saluggia, Italy) and subareolar subcutaneous injection of blue dye (Patent Blue V®,
Laboratoire Guerbet, Aulnay-sous-Bois, France). Technetium-99m was injected 16–18 h
before surgery and blue dye was injected 5 min prior to incision to identify the SLN.
Hot and blue nodes were removed and frozen section was performed immediately. If SLN/s
were negative in frozen section, patients had no further ALND. All patients received
whole-breast irradiation after surgery. No radiotherapy to the axilla was performed.
Adjuvant chemotherapy was administered before radiotherapy when indicated. Adjuvant
endocrine treatment was initiated after surgery. The decision to use adjuvant chemotherapy
or hormone therapy was mainly based on prognostic factors from the primary breast
tumour such as tumour size, hormone receptor status and/or HER-2/neu status. Additionally,
node-positive patients received adjuvant hormone therapy by participating in the national
hormone treatment trial.
Assessments
Frequency
Data were collected at three time points: before surgery (t1), 1 week after discharge
(t2), and 9–12 months after surgery (t3).
EORTC QLQ-C30
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
QLQ-C30, version 3.0, a cancer-specific questionnaire, is composed of five functional
scales (physical, role, emotional, cognitive, social), the global health status and
nine symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite
loss, constipation, diarrhoea, financial difficulties). The global health status correlates
significantly with all the functional and symptom scales (Aaronson et al, 1993). For
the functional and global QOL scales a higher score indicates a better level of functioning.
All patients answered this questionnaire before surgery (t1), 1 week after discharge
(t2) and 9–12 (t3) months after surgery.
EORTC QLQ-BR23
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
QLQ-BR23, the breast cancer module, incorporates four symptom scales (systemic therapy
side effects, breast symptoms, arm symptoms, upset by hair loss) and four functional
scales (body image, sexual functioning, sexual enjoyment, future perspective). All
scores obtained from scales and single items range from 0 to 100. A higher score indicates
a better level of functioning. All patients answered this questionnaire before surgery
(t1), and 9–12 months after surgery (t3).
Range of arm/shoulder motion
All patients underwent goniometric measurement of the affected arm by a physiotherapist
at every time point. Measurements of the following arm movements were obtained: shoulder
flexion, shoulder extension, shoulder abduction, horizontal abduction and horizontal
adduction.
McGill Pain Questionnaire
German version (Melzack, 1975; Stein and Mendl, 1988). This questionnaire is composed
of sensory, affective, evaluative word descriptors in the form of 78 words grouped
into 20 subclasses used by patients to specify subjective pain experience and of a
visual analogue pain scale for measurement of pain intensity. The questionnaire provides
information about the site of pain and the relative effects of a given manipulation
on several dimensions of pain. All patients completed the questionnaire at every time
point.
Karnofsky performance status scale (KPS)
The KPS scale consists of 11 components describing patients' mobility and ability
to maintain employment, live at home and care for oneself. The scores used by clinicians
range from 0 (worst physical condition) to 100 (best physical status).
Statistical analysis
Statistical methodology was used in accordance with The EORTC QLQ-C30 Scoring Manual
(Fayers et al, 1999). In order to compare both types of surgery (ALND vs SLNB) nonparametric
independent two-sided tests were applied (Wald–Wolfowitz test, Kolmogorov–Smirnov
test, Mann–Whitney U-test) to all variables tested. Differences of the proportions
of patients reporting pain after ALND over time were analysed using the Cochran's
Q test. The same test was applied for analysis of the SLNB group. A P-value less than
5% was considered as significant.
RESULTS
In all, 56 breast cancer patients participated in this study. Patients' clinical and
demographic characteristics are summarized in Table 1
Table 1
Patient characteristics
Total sample(n=56)
ALND(n=31)
SLNB(n=25)
P-value
Age (years)
Mean
60.1
57.7
61.4
0.27
Site of axillary surgery (%)
Right axilla
51.7
54.8
48.0
0.62
Left axilla
48.3
45.2
52.0
0.6
Cancer type (%)
Invasive ductal
62.5
64.5
56.0
0.52
Invasive lobular
14.3
6.5
24.0
0.07
Invasive ductal and intraductal
23.2
29.0
20.0
0.44
Tumour size (%)
pT1
71.4
74.2
68.0
0.62
pT2
28.6
25.8
32.0
0.62
Adjuvant treatment (%)
HT and RT
67.9
67.7
68.0
0.62
CT and RT
23.2
29.0
20.0
0.44
RT alone
8.9
3.3
12.0
0.22
Menopausal status (%)
Premenopausal
28.6
35.5
20.0
0.20
Postmenopausal
71.4
64.4
80.0
0.20
Civil status (%)
Married/partnership
53.6
58.1
48.0
0.45
Single/widowed/divorced
30.4
35.5
24.0
0.36
Unknown
16.0
6.4
28.0
0.03
Education (%)
Primary
44.6
51.6
40.0
0.39
Secondary/professional
25.0
25.8
24.0
0.86
Higher
14.3
16.1
12.0
0.66
Unknown
16.1
6.5
24.0
0.06
HT=hormone therapy; RT=radiotherapy; CT=chemotherapy.
. The mean number of lymph nodes dissected was 2.2 in group I and 15.0 in group II.
The percentage of postmenopausal patients was 71.4%. Preoperative arm symptoms, the
Karnofsky performance status and QOL levels were comparable between both groups. Table
2
Table 2
Means (s.d.) of the EORTC QLQ-C30 scale scores
ALND
SLNB
P-value
Before surgery (t1)
Global QOL
63.8 (24.9)
55.9 (25.9)
0.87
Physical functioning
87.7 (19.2)
90.8 (17.9)
0.69
Role functioning
88.0 (26.1)
90.9 (17.7)
0.69
Emotional functioning
65.3 (21.6)
53.8 (31.1)
0.05
Cognitive functioning
80.6 (21.9)
84.0 (23.8)
0.41
Social functioning
85.9 (23.6)
84.8 (22.3)
0.75
Pain
14.1 (23.2)
18.7 (27.0)
0.90
After discharge (t2)
Global QOL
57.8 (20.5)
68.5 (17.0)
0.58
Physical functioning
82.3 (15.4)
86.7 (14.9)
0.37
Role functioning
60.2 (28.0)
70.4 (30.9)
0.37
Emotional functioning
75.6 (21.3)
70.7 (27.3)
0.07
Cognitive functioning
86.1 (22.3)
90.7 (14.7)
0.65
Social functioning
78.7 (28.4)
83.4 (22.0)
0.65
Pain
34.3 (29.2)
16.7 (20.4)
<0.05a
9–12 months after surgery (t3)
Global QOL
72.1 (22.7)
70.2 (20.3)
0.45
Physical functioning
85.9 (21.4)
87.2 (18.2)
0.34
Role functioning
74.1 (27.6)
78.3 (26.8)
0.63
Emotional functioning
68.9 (19.8)
70.5 (25.4)
0.63
Cognitive functioning
77.6 (25.3)
82.6 (24.8)
0.21
Social functioning
86.2 (23.6)
89.8 (19.9)
0.50
Pain
21.3 (25.9)
18.8 (24.8)
0.29
a
Statistically significant.
provides QOL levels (EORTC QLQ-C30) at all time points of assessment. The mean scores
at baseline assessment (t1) showed that patients' global QOL and emotional functioning
were more affected in both groups than physical functioning, role functioning, cognitive
functioning and social functioning. However, significant improvement of global QOL
(P=0.002) occurs at t2 only in patients after SLNB (Figure 1
Figure 1
Comparison of global QOL (means) after ANLD vs SLNB over time.
). Analysis of means of symptom scales shows significant higher levels of pain at
t2 in patients after ALND (P=0.03) (Figure 2
Figure 2
Comparison of pain (means) after ALND vs SLNB over time.
). Comparison of QOL dimensions assessed by the EORTC QLQ-C30 and QLQ-BR23 (Tables
2 and 3
Table 3
Means (s.d.) of the EORTC QLQ-BR23 scale scores and Karnofsky performance status
ALND
SLNB
P-value
Before surgery (t1)
Body image
89.9 (18.3)
83.2 (23.7)
0.39
Sexual functioning
30.9 (31.9)
28.7 (27.7)
0.69
Sexual enjoyment
61.5 (38.1)
52.3 (32.5)
0.95
Future perspective
38.8 (33.9)
31.8 (39.5)
0.56
Arm symptoms
8.3 (14.4)
19.5 (25.2)
0.07
KPS
98.2 (4.6)
99.1 (2.8)
0.10
9–12 months after surgery (t3)
Body image
87.9 (15.8)
92.0 (13.6)
0.45
Sexual functioning
33.4 (33.4)
35.1 (24.8)
0.45
Sexual enjoyment
63.9 (26.4)
66.7 (23.5)
0.20
Future perspective
56.7 (32.9)
54.5 (34.9)
0.18
Arm symptoms
21.2 (22.8)
14.0 (18.4)
0.26
KPS
96.1 (18.1)
99.5 (2.0)
0.21
) shows no statistically significant differences among patients in both groups before
surgery (t1). At t3, global QOL improved in both groups, but there were no statistically
significant differences in any dimension of QOL. Karnofsky performance scores at baseline
were high in both groups and showed no significant changes over time (Table 3).
Analysis of arm/shoulder mobility assessment data showed significant impairment of
abduction and flexion in the operated arm at the time points t2, t3 and of horizontal
adduction at the time point t3 in group II (Table 4
Table 4
Means (s.d.) arm/shoulder motion, goniometric measurement
ALND
SLNB
P-value
Before surgery (t1)
Abduction
153.7 (19.3)
160.4 (10.9)
0.75
Flexion
152.1 (17.9)
153.6 (13.6)
0.58
Extension
50.7 (8.4)
49.3 (5.8)
0.55
Horizontal abduction
108.6 (12.8)
108.1 (12.4)
0.55
Horizontal adduction
35.1 (14.0)
32.2 (8.2)
0.98
After discharge (t2)
Abduction
128.3 (24.9)
152.3 (13.7)
0.013*
Flexion
134.8 (21.9)
150.6 (16.1)
0.04*
Extension
48.6 (11.5)
51.7 (5.0)
0.58
Horizontal abduction
106.1 (15.8)
108.4 (13.2)
0.72
Horizontal adduction
29.5 (14.4)
29.4 (11.3)
0.72
9–12 months after surgery (t3)
Abduction
143.8 (22.8)
158.9 (13.9)
0.007*
Flexion
146.0 (15.9)
154.6 (15.0)
0.03*
Extension
47.1 (11.2)
52.2 (27.1)
0.39
Horizontal abduction
101.1 (15.9)
106.5 (21.3)
0.76
Horizontal adduction
34.5 (14.1)
35.6 (19.1)
0.011*
*
P<0.05.
).
Analysis of data assessed by the McGill Pain Questionnaire showed significantly more
sensory problems of the affected arm in group II at t3 when the number of words chosen
(NWC) was compared with those of group I. Severity of pain measured by the visual
analogue scale showed that women in group II reported significantly greater pain than
in group I at t3 (Table 5
Table 5
Means (s.d.) for pain
ALND
SLNB
P-value
After discharge (t2)
Sensory (NWC)
2.29 (2.67)
0.88 (1.45)
0.552
Visual analogue scale
1.45 (1.36)
0.68 (1.03)
0.823
9–12 months after surgery (t3)
Sensory (NWC)
1.45 (2.29)
0.96 (2.46)
0.026*
Visual analogue scale
1.13 (1.36)
0.68 (1.63)
0.012*
*
P<0.05.
).
Arm/shoulder pain was reported in only 36% of patients after SLNB in comparison to
68% after ALND at t2. While the number of patients with pain decreased significantly
over time in the ALND group at t3 (Cochran's Q, P=0.008), no significant changes could
be found in the SLNB group (P=0.08). Arm symptoms assessment by the EORTC QLQ-BR23
questionnaire showed no significant difference in both the groups at t3 (Table 3).
DISCUSSION
The present study confirms previous observations suggesting that SLNB is associated
with less arm/shoulder morbidity (Giuliano et al, 2000; Schrenk et al, 2000; Burak
et al, 2002; Haid et al, 2002; Temple et al, 2002) than ALND. Evaluation and comparison
of QOL outcomes in a short time follow-up in breast cancer patients undergoing ALND
or SLNB after breast-conserving surgery provides additional observations:
(1) The type of axillary surgery does not seem to have an impact on global QOL, but
may affect other QOL aspects as pain. (2) Body image and sexual functioning remain
stable during the postsurgery follow-up in both types of axillary surgery. (3) The
SLNB is associated with mild pain and mild sensory morbidity, significantly less than
ALND, improving during the months following surgery. (4) Arm/shoulder abduction, flexion
and horizontal adduction show significant impairment after ALND when compared with
the preoperative range of motion.
The examination of postsurgery side effects after the different types of axillary
surgery in our sample showed a significant difference in pain severity as well as
in intensity of sensory morbidity of the affected arm after SLNB in comparison to
ALND. Numbness was reported in 19.3% of the patients after ALND in contrast to 4%
in the SLNB group, whereas ‘tugging’ was the most common complaint in both groups.
The NWC shows that even after SLNB, a few patients experience substantial sensory
complaints of the affected arm at t3. The properties of the McGill Pain Questionnaire
in this matter are (1) exclusion of patients reporting breast pain, (2) specification
of subjective pain intensity and (3) description of sensory qualities of pain by word
descriptors as ‘numbing’, ‘tugging’, etc. Interestingly, evaluation of pain using
the McGill Pain Questionnaire, the QLQ-C30 questionnaire and evaluation of ‘arm symptoms’
using the QLQ-BR23 questionnaire show some discrepancy. These results support the
hypothesis, that current standard questionnaires do not cover all aspects of QOL (Janni
et al, 2001). Several aspects of morbidity including pain, range of motion and sensory
complaints of the affected arm have been reported to show significant difference in
favour of SLNB (Giuliano et al, 2000; Schrenk et al, 2000; Burak et al, 2002; Haid
et al, 2002; Temple et al, 2002). However, measuring instruments and scoring systems
used in these studies differ widely.
In our study, patients' clinical and sociodemographic characteristics regarding age,
tumour stage, adjuvant treatment were well balanced between the two groups. Using
the EORTC QOL-C30 questionnaire, no significant difference could be detected in global
QOL after ALND and SLNB at a short time follow-up. Interestingly, baseline assessment
showed low levels of patients' global QOL in both groups increasing during follow-up.
Statistically significant higher levels of global QOL are observed at t2 and t3 after
SLNB, when compared with baseline levels. In contrast, impairment of global QOL at
t2 after ALND clearly shows a difference in QOL improvement in favour of the SLNB
group. We suggest that this is because patients in the SLNB group recover sooner than
after ALND. However, patients having positive nodes in the ALND group reflect a more
advanced disease. Randomised trials, as the ALMANAC trial, can possibly demonstrate
the impact of axillary status on QOL. In addition to global QOL, assessment of emotional
functioning shows low levels at baseline too, with no significant changes during follow-up
in both groups. An explanation for low levels at baseline is that patients being informed
about the breast cancer diagnosis before surgery induced psychological distress (Fallowfield
et al, 1986; Ganz et al, 1992; Coscarelli Schag et al, 1993). In this study the Karnofsky
performance status score was, for most patients, over 90 at baseline and showed no
differences in patients' physical condition in both groups during follow-up. Using
the EORTC QLQ-BR23 questionnaire comparison of body image and sexual functioning showed
no difference between the two groups.
In the present study, we used a variety of validated measurement instruments to specify
reliably patients' subjective experience of postoperative morbidity and QOL after
SLNB in comparison to ALND. To our knowledge, this is one of the first reports to
compare various aspects of QOL and arm/shoulder morbidity after different types of
axillary surgery considering presurgery assessments. However, despite the analysis
of many covariates with different measurement instruments a potential limitation of
our study may be the small sample size.
In conclusion, the SLNB as a minimal invasive technique for axillary staging seems
to be an alternative to ALND associated with a better postsurgery arm/shoulder mobility,
with less pain and less sensory morbidity of the affected arm in a short-time follow-up.
Severity of post-treatment side effects and QOL aspects should be considered when
counselling breast cancer patients.