Axillary lymph node metastases detection with 99mTc-sestamibi scintimammography in patients with breast cancer undergoing curative surgery.

Abstract

Axillary lymph node (AN) status is the primary prognostic discriminant in patients with breast cancer (BC). Although axillary dissection represents the method of choice for obtaining such information, less invasive procedures have been suggested. The aim of this study was to evaluate the usefulness of 99mTc-sestamibi scintimammography (SSM) in detecting AN involvement in patients with confirmed primary BC undergoing surgery.
A series of 159 consecutive women (median age 54 years, range 36-78 years) with confirmed BC undergoing curative surgery were enrolled in the study. Each patient underwent SSM, from 4 to 12 days prior to surgery. According to the tumour staging, modified radical mastectomy was performed in 41 (25.8%) patients, while 118 (74.2%) patients underwent breast conserving surgery with dissection of the axilla. The results of SSM were compared against the final histological evaluation of the axillary nodes.
The final pathology showed 33 (20.8%) pT1b, 90 (56.6%) pT1c, and 36 (22.6%) pT2 breast carcinomas. The greatest diameter of the tumour ranged from 8 to 30 mm (median 16 mm). Sixty patients (37.7%) had axillary node metastases (N1), and 99 (60.3%) had negative nodes (NO). The age of the patients significantly correlated with both size of the tumour (R=0.24, p<0.01) and number of positive nodes (R=0.33, p<0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SSM in detecting AN metastases were 81.4%, 91.0%, 84.2%, 91.0% and 87.4%, respectively. The sensitivity was higher in patients with three or more positive nodes (27 out of 28, 96.4%), while in patients with two (n=25) or one (n=7) positive nodes, the sensitivity decreased to 80% and 28.6%, respectively.
SSM may be useful in patients undergoing surgery for BC when a preoperative assessment of axillary lymph node status is required. Unfortunately, the sensitivity of SSM in detecting node metestases in patients with BC is low when the number of involved nodes is two or less. This suggests that other imaging techniques should be used is conjunction with SSM, with the aim of increasing both sensitivity and specificity.

Full text

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Abstract. Background: Axillary lymph node (AN) status is
the primary prognostic discriminant in patients with breast
cancer (BC). Although axillary dissection represents the
method of choice for obtaining such information, less
invasive procedures have been suggested. The aim of this
study was to evaluate the usefulness of 99mTc-sestamibi
scintimammography (SSM) in detecting AN involvement in
patients with confirmed primary BC undergoing surgery.
Patients and Methods: A series of 159 consecutive women
(median age 54 years, range 36-78 years) with confirmed BC
undergoing curative surgery were enrolled in the study. Each
patient underwent SSM, from 4 to 12 days prior to surgery.
According to the tumour staging, modified radical
mastectomy was performed in 41 (25.8%) patients, while 118
(74.2%) patients underwent breast conserving surgery with
dissection of the axilla. The results of SSM were compared
against the final histological evaluation of the axillary nodes.
Results: The final pathology showed 33 (20.8%) pT1b, 90
(56.6%) pT1c, and 36 (22.6%) pT2 breast carcinomas. The
greatest diameter of the tumour ranged from 8 to 30 mm
(median 16 mm). Sixty patients (37.7%) had axillary node
metastases (N1), and 99 (60.3%) had negative nodes (N0).
The age of the patients significantly correlated with both size
of the tumour (R=0.24, p<0.01) and number of positive
nodes (R=0.33, p<0.01). The sensitivity, specificity, positive
predictive value, negative predictive value and accuracy of
SSM in detecting AN metastases were 81.4%, 91.0%, 84.2%,
91.0% and 87.4%, respectively. The sensitivity was higher in
patients with three or more positive nodes (27 out of 28,
96.4%), while in patients with two (n=25) or one (n=7)
positive nodes, the sensitivity decreased to 80% and 28.6%,
respectively. Conclusion: SSM may be useful in patients
undergoing surgery for BC when a preoperative assessment of
axillary lymph node status is required. Unfortunately, the
sensitivity of SSM in detecting node metestases in patients
with BC is low when the number of involved nodes is two or
less. This suggests that other imaging techniques should be
used is conjunction with SSM, with the aim of increasing
both sensitivity and specificity.
Axillary lymph node (AN) status is the primary prognostic
discriminant in patients with breast cancer (BC).
Although axillary dissection represents the method of
choice for obtaining such information, less invasive
procedures have been suggested. Preoperative non-
surgical techniques include axillary ultrasonography (US)
with or without US-guided fine-needle aspiration cytology
(FNAC) or core-biopsy, fluorine-18-fluorodeoxyglucose
(18-FDG) positron emission tomography (PET) and
99mTc-sestamibi scintimammography (SSM).
The aim of this study was to evaluate the usefulness of
SSM in detecting AN involvement in patients with
confirmed primary BC undergoing surgery.
Patients and Methods
Study population. A series of 159 consecutive women (median age
54 years, range 36-78 years) with BC confirmed by FNAC, core
biopsy or open biopsy undergoing curative surgery were enrolled
2949
*Presented in part at the 12th European Cancer Conference
(ECCO 12), Copenhagen (Denmark), September 21-25, 2003.
Correspondence to: Prof. F. Lumachi, University of Padua, School
of Medicine, Breast Surgery Unit, Department of Surgical and
Gastroenterological Sciences, via Giustiniani 2, 35128 Padova,
Italy. Tel: +39 049 821 1812, Fax: +39 049 656 145, e-mail:
flumachi@unipd.it
Key Words: Breast cancer, scintimammography, axillary node
metastases.
ANTICANCER RESEARCH 27: 2949-2952 (2007)
Axillary Lymph Node Metastases Detection with
99mTc-sestamibi Scintimammography in Patients with
Breast Cancer Undergoing Curative Surgery*
FRANCO LUMACHI1, GUIDO FERRETTI2, MICHELE POVOLATO2, FRANCO BUI3, DIEGO CECCHIN3,
MARIA CRISTINA MARZOLA3, PIETRO ZUCCHETTA3and UMBERTO BASSO4
1Breast Surgery Unit, Department of Surgical and Gastroenterological Sciences,
3Nuclear Medicine Service, Department of Diagnostic Medical Sciences,
University of Padua, School of Medicine, 35128 Padova;
2Nuclear Medicine Service, S.M. Misericordia Hospital, 33100 Udine;
4Division of Medical Oncology, Istituto Oncologico Veneto, IRCCS, 35128 Padova, Italy
0250-7005/2007 $2.00+.40

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in the study. In patients with non-palpable masses the biopsy was
performed using a wire needle localization, under US or
stereotactic guidance. There were 44 (27.7%) premenopausal and
115 (73.3%) post-menopausal women.
Once they had given informed consent, each patient underwent
SSM, from 4 to 12 days prior to surgery. According to the tumour
staging, modified radical mastectomy was performed in 41 (25.8%)
patients, while 118 (74.2%) patients underwent breast conserving
surgery with AN dissection.
The greatest diameter (size) of the tumour (pT) was
measured by the pathologist, and the final diagnosis was
obtained by routinely stained serial sections (1 mm of
thickness). The results of SSM were compared against final
histological evaluation of AN.
99mTc-sestamibi scintimammography. According to the procedure
guidelines suggested by The Society of Nuclear Medicine (SNM), a
single dose (750 MBq) of
butylisonitrile) was injected in the arm contralateral to the side of
the lesion (1). A triple head gamma camera (Philips Irix) equipped
with a parallel-hole low-energy high-resolution collimator
(resolution 7.5 mm at 10 cm), a 140 keV (10% window) energy
setting and a 256x256 matrix was used.
To improve the visualization of the axilla, patients were in prone
position, with arms raised above the head, and the images were
acquired 5-10 min after intravenous injection of the radio-
pharmaceutical (2).
Planar (prone lateral, anterior and posterior oblique) images
combined with SPECT (128 x 128 matrix, 64 steps, 30 sec/step,
180Æ acquisition) images were obtained. A focal uptake of the
99mTc-sestamibi, and a mass-to-background ratio of more than 1.4
was considered as a positive result, as previously reported (3, 4).
99mTc-sestamibi (methoxyiso-
Definitions and statistical analysis. The tumours were classified
according to the TNM classification: pT1b=6-10 mm in size
(greatest diameter measured by the pathologist), pT1c=11-20 mm,
pT2=21-50 mm; pN0=no lymph node metastases, pN1=metastases
in at least one axillary node (5).
A positive result of SSM identified the presence of one or more
metastatized AN. Sensitivity was defined as true-positives (TP)/TP
+ false-negatives (FN), specificity as true-negatives (TN)/TN +
false-positives (FP), positive predictive values (PPV) as TP/(TP +
FP), negative predictive values (NPV) as TN/(TN + FN), and
accuracy as (TN + TP)/overall patients.
The reported data are in part expressed as mean±standard
deviation (SD). The Mann-Whitney U-test and the Pearson’s
correlation coefficient (R) calculation were used for the
comparison of qualitative variables in the case of non-normal
distribution and to evaluate the linear relationship between pairs
of variables, respectively. Comparisons between groups were
performed using the Student’s t-test, when required. The
differences were considered significant at a p-value <0.05.
Results
The size of the tumours ranged from 8 mm to 30 mm
(median 16 mm). Table I reports the histological type of the
tumours, and the pathological staging at final pathology.
Sixty patients (37.7%) had axillary node metastases (N1)
and 99 (60.3%) had negative nodes (N0). The average
number of removed nodes was 19.9±2.1 and the mean
number of positive nodes was 2.7±1.2.
The age of the patients significantly correlated with both size
of the tumour (R=0.24, F=9.55, p=0.002) and number of
positive nodes (R=0.33, F=7.11, p<0.009). As expected, there
was a direct relationship (R=0.31, F=6.08, p=0.016) between
the size of the tumour and the number of positive nodes.
The sensitivity, specificity, PPV, NPV, and accuracy of
SSM in detecting AN metastases are reported in Table II.
ANTICANCER RESEARCH 27: 2949-2952 (2007)
2950
Table I. Histological type of the tumour, and pathological staging at final
pathology.
Characteristics N0% N1% Overall%
Overall patients 9962.3% 6037.7% 159
Histological type
Infiltrating ductal
Infiltrating lobular
Medullary
Other and mixed
8383.8%
7.1%
3.0%
6.1%
5693.3%
1.7%
-
5.0%
13987.4%
5.0%
1.9%
5.7%
7
3
6
1
0
3
8
3
9
Pathological tumour stage
pT1b
pT1c
pT2
31
66
31.3%
66.7%
2.0%
23.3%
40.0%
56.7%
33
90
36
20.8%
56.6%
22.6%
24
342
N0=number of patients with negative nodes, N1=number of patients
with involved nodes.
Table II. Results of 99mTc-sestamibi scintimammography in detecting
axillary node metastases.
TP FP TN FNSensitivity SpecificityPPVNPVAccuracy
489 911181.4% 91.0%84.2%91.0%87.4%
TP=true-positives, FP=false-positives, TN=true-negatives, FN=false-
negatives, PPV=positive predictive value, NPV=negative predictive
value.
Table III. Main differences between patients with true-positive and false-
negative scintimammorgaphy.
CharacteristicsTrue-positives
p-value False-negatives
Number of patients
Age (years)
Size of the tumour (mm)
Number of removed nodes
Number of positive nodes
48
58.8±7.7
21.2±4.5
19.9±2.1
3.0±1.2
- 11
48.6±10.3
18.2±5.4
19.7±2.0
1.6±0.7
<0.001
0.06
0.77
<0.001

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Patients with false-negative SSM were significantly (p<0.01)
younger than those in whom the imaging technique
correctly detected involved AN (Table III). Moreover, the
number of removed AN did not differ (p=NS) between
patients with true-positive and false-negative SSM, while the
number of metastatized AN was significantly (p<0.05) lower
in those not correctly diagnosed.
The sensitivity was higher in patients with three or more
positive nodes (27 out of 28, 96.4%), while in patients with
two (n=25) or one (n=7) positive nodes, the sensitivity
decreased to 80% and 28.6%, respectively.
Discussion
The usefulness of SSM in detecting primary BC and AN
involvement has long been reported (6-9). SSM is the method
by which BC may be
radiopharmaceutical, whether tumour specific (i.e.99mTc-
sestamibi) or non-specific (i.e.99mTc-methylene diphospho-
nate) (10). Although 99mTc-sestamibi is not really tumour
specific it is currently used in performing SSM, according to
the SNM guidelines (11, 12). The sensitivity and specificity of
SSM in the detection of AN involvement range from 68% to
82%, and from 87% to 100%, respectively, especially when
two or more AN are involved (3, 13-15). A few studies report
worse results (16, 17). Unfortunately, in patients with BC the
tumour-to-background ratio mainly correlates with the size
of the tumour (18). A direct relationship between AN uptake
of the radiopharmaceutical and the number of involved nodes
or the mass of metastatic tissue should be considered.
The AN status can be preoperatively evaluated also by
using axillary US, US-guided FNAC, and 18-FDG PET. We
have found 68% sensitivity and 80% specificity by using
axillary US alone, while a protocol based on US in
conjunction with US-guided FNAC or core biopsy may
reach 78-86% sensitivity in detecting preoperatively
involved nodes (2, 19-21). The sensitivity and specificity of
18-FDG PET range between 61% and 93%, and between
79% and 92%, with a mean of 75% and 83%, respectively
(22-24).
Thus, the results obtained with SSM are similar to those
obtained by using other imaging techniques. However, US-
guide FNAC requires the presence of the cytopathologist
during the entire procedure, and 18-FDG PET is expensive
and not available everywhere (2).
In conclusion, SSM may be useful in patients undergoing
surgery for BC when a preoperative assessment of axillary
lymph node status is required. Unfortunately, the sensitivity
of SSM in detecting AN metastases in patients with BC is
low when the number of involved nodes is two or less. This
suggests that other imaging techniques should be used in
conjunction with SSM, with the aim of increasing both its
sensitivity and specificity.
identified by using a
Acknowledgements
The authors are grateful to Dr. Annamaria Grigio and Miss
Federica De Lotto for help in writing the manuscript and for
reviewing the English.
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Received April 2, 2007
Revised May 25, 2007
Accepted May 29, 2007
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