―Report on Experiments and Clinical Cases―
Evaluation of Sentinel Lymph Node Biopsy in Clinically Node-Negative Breast Cancer Shinya Iida1, Shunsuke Haga1, Koji Yamashita2, Keiko Yanagihara1, Tomoko Kurita1, Ryusuke Murakami3, Shin-ichiro Kumita3, Shin-ichi Tsuchiya4, Kiyonori Furukawa1 and Eiji Uchida1 1
Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School
2
Department of Biological Regulation and Regenerative Surgery, Graduate School of Medicine, Nippon Medical School 3
Department of Clinical Radiology, Graduate School of Medicine, Nippon Medical School 4
Department of Diagnostic Pathology, Nippon Medical School Hospital
Abstract Background: In patients with clinically node-negative breast cancer, diagnosed with palpation and several types of imaging examination, sentinel lymph nodes accurately predict the status of the other axillary nodes, which determine the nature of subsequent adjuvant treatment. In addition, compared with axillary lymph node dissection, sentinel-node biopsy results in less postoperative morbidity, including pain, numbness, swelling, and reduced mobility in the ipsilateral arm. Methods: We analyzed the validity of the sentinel node biopsy procedure using dual-agent injection of blue dye and radioactive colloid performed in our hospital from May 2006 through March 2010. A total of 258 breasts of 253 patients were studied. Simultaneous axillary lymph node dissection was performed only if rapid intraoperative diagnosis identified metastasis in sentinel lymph nodes. The identification rate, accuracy, provisional false-negative rate, which was calculated with data from all 65 patients whose sentinel lymph nodes had metastasis, and axillary recurrence rate of sentinel node biopsy were calculated. Results: The sentinel node identification rate was 99.2%, and the accuracy of sentinel lymph node status was 98.0%. The provisional false-negative rate was 7.7%. During an observation period averaging 24 months, axillary recurrence was observed in only 1 of 256 cases (0.4%), and there were no cases of parasternal recurrence. In patients who underwent sentinel-node biopsy without axillary lymph node dissection, there was no obvious morbidity. Conclusion: Our sentinel-node biopsy procedure yielded satisfactory results, which were not inferior to the results of previous clinical trials. Thus, we conclude our sentinel-node biopsy procedure is feasible. If the efficacy and safety of sentinel-node biopsy are confirmed in several large-scale randomized controlled trials in Europe and the United States, sentinel-node biopsy will become a standard surgical technique in the management of clinically node-negative breast cancer. (J Nippon Med Sch 2011; 78: 96―100) Key words: breast cancer, sentinel lymph node, sentinel-node biopsy, sentinel lymph node biopsy
Correspondence to Shinya Iida, MD, Division of Breast Oncology, Department of Surgery, Nippon Medical School Hospital, 1―1―5 Sendagi, Bunkyo-ku, Tokyo 113―8603, Japan E-mail:
[email protected] Journal Website (http:! ! www.nms.ac.jp! jnms! ) 96
J Nippon Med Sch 2011; 78 (2)
Sentinel Node Biopsy in Breast Cancer
breast. Written informed consent was obtained from all
Introduction
patients, and the study was approved by the Axillary lymph node status is an important
institutional review board of the hospital. In October
prognostic factor in breast cancer which determines
2008, we joined a multicenter-based phase II study
1
the nature of subsequent adjuvant treatment .
of the safety of SNB for primary breast cancer
However, reports indicate that axillary lymph node
without axillary lymph node metastasis10.
dissection
( ALND )
results
in
postoperative
morbidities, including pain, numbness, swelling, and
The Combined SNB Procedure
2,3
reduced mobility in the ipsilateral arm .
Dual-agent SLN mapping was performed as
On the other hand, patients who undergo only
follows: 3.0 to 7.4 MBq of technetium-99m-labeled
sentinel node biopsy (SNB) have less postoperative
particles of phytic acid in 1 mL of saline was injected
2,3
morbidity than do patients who undergo ALND .
into the intracutaneous region of the areola 2 to 19
Findings from sentinel lymph nodes (SNLs) could
hours
accurately predict the status of the other axillary
lymphoscintigraphy (LS) was performed 2 to 3 hours
lymph nodes in clinically node-negative breast
after radiotracer injection. The blue dye used was 1
4
before
surgery.
Preoperative
cancer . SNB is performed in some countries, despite
to 2 mL (4―8 mg) of indigo carmine (Daiichi-Sankyo
limited data from randomized trials on morbidity
Co. Ltd., Tokyo, Japan). The dye was injected
and mortality outcomes5,6.
without massage at an intracutaneous site above the
A standard protocol for SNB has not been
tumor when the tumor was located mainly in the C
established. In our hospital, we have performed SNB
area9 or was injected at the areola if the tumor was
since 2005 for patients with early breast cancer.
located mainly in other areas. The gamma probe
7
Initially, a dye-guided method was used. Previously,
(GP) used was the Navigator GPS (Covidien Japan
we performed a feasibility study using findings from
Inc., Tokyo, Japan). Rapid intraoperative pathological examinations
back-up ALND, and qualified ourselves to omit ALND after SNB on the basis of criteria described 8
used
2-mm-thick
frozen
sections
stained
with
in a previous report . We introduced an SNB method
hematoxylin and eosin. Final pathological diagnostic
using
examinations were performed postoperatively with
dual-agent
injection
of
blue
dye
and
radioactive colloid in May 2006. In the present study,
permanent
we analyzed the validity of this dual-guided SNB
sections stained with hematoxylin and eosin.
paraffin-embedded
Simultaneous ALND was performed only if a
procedure now performed in our hospital.
rapid Materials and Methods
formalin-fixed,
intraoperative
identified
metastasis
diagnostic in
SLNs.
examination Because
we
discontinued back-up ALND, we were unable to Patients
calculate the exact false-negative rate. Instead, the
The study comprised 258 breasts (i.e., 258 cases) of
provisional false-negative rate was calculated using
253 patients who underwent surgery for primary
data
breast cancer at our hospital from May 2006
metastasis. A false-negative case was defined as one
through March 2010. The clinical diagnosis for all
in
patients was node-negative breast cancer (Tis or T1-
intraoperative
3, N0, M0)9. The 258 cases included 2 cases in men, 5
was subsequently detected on final diagnostic
cases of multifocal breast cancer (i.e., multiple
examination. Cases were not classified as false
cancers in the same breast quadrant), and 4
negatives if intraoperative diagnostic examination
postexcisional biopsy cases. We excluded patients
returned a negative result for SLN metastasis, but
who had received neoadjuvant chemotherapy and
only micrometastasis9 was subsequently detected on
those in whom cancer had recurred in the same
examination of permanent sections.
J Nippon Med Sch 2011; 78 (2)
from
which
all
65
patients
metastasis
was
whose not
examination, but
SLNs
identified
had with
macrometastasis
97
S. Iida, et al
Table 1 The results of SNB in this study Metastasis in Axillary Lymph Nodes
Positive Negative
Metastasis in SLNs Total
Total
Positive
Negative
60 5
0 191
60 196
65
191
256
Provisional false negative rate ＝ 7.7% (5/65) Accuracy ＝ 98.0% (251/256)
Patients
with
false-negative
results
discussed
treatment
physician-in-charge
the
detected with GP were as follows: 1) LS=GP: 66.1%
options,
(125 of 189 cases); 2) LS>GP: 5.3% (10 cases); and 3)
and
which included 2-stage ALND, postoperative axillary
LS
