Japanese Journal of Clinical Oncology 31:318-321 (2001)
© 2001 Foundation for Promotion of Cancer Research
Management of the Axilla in Breast Cancer: a Comparative Study Between Sentinel Lymph Node Biopsy and Four-node Sampling Procedure
1Department of Surgery I, 2Department of Pathology II, 3Department of Radiology and 4Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: The aim of this study was to compare the efficacy of sentinel lymph node biopsy and that of four-node sampling for predicting other nodal status in breast cancer.
Methods: 206 patients with operable breast cancer were enrolled. The identification of sentinel lymph nodes (SLNs) was carried out in 110 patients using a gamma probe after injection of radioactive tin colloids. Four palpable lymph nodes (FNs) were removed from the lower axilla at the first step of axillary dissection in 98 patients. The predictive value of nodal status was compared between SLNs and FNs, based on the pathological findings of all dissected lymph nodes. To examine the relationship between SLNs and FNs, we chose the FNs retrospectively (defined as rFNs) from among all nodes in SLNs.
Results: SLNs were identified in 108 (98%) of 110 patients. With one patient having skip metastasis, the accuracy and sensitivity were 99 and 98%, respectively. In the four-node sampling (FNS) group, two in 98 patients had skip metastasis and the accuracy and sensitivity were 98 and 96%, respectively. Findings on the relationship between these methods of biopsy were as follows: (i) rFNs included SLNs in 79 patients (73%); (ii) rFNs partially included SLNs in 24 patients (22%); and (iii) no relationship was evident in five patients (5%).
Conclusions: The accuracy/sensitivity of FNs was comparable to that of SLNs. FNS can be considered to represent a highly promising approach and may be used as an alternative procedure that can be performed safely and easily in any institute.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The relatively low rate of axillary lymph node metastasis in patients with early-stage breast carcinoma and the morbidity associated with complete axillary lymph node dissection have brought the routine use of lymph node dissection into question. In fact, over 50% of tumors up to 5 cm in diameter and 90% of those <1 cm have no involvement of axillary nodes (1). However, there is no reliable preoperative method of determining axillary node involvement (2–4).
The 1990s saw an increasing use of the sentinel lymph node biopsy (SLNB) technique (5–8). On the other hand, histological examination of axillary nodes obtained by a four-node sampling procedure (FNS), the aim of which was to obtain at least four palpable lymph nodes from the axilla starting at the axillary tail, has been shown to stage the axilla accurately (9). Chetty et al. (10) recently reported results from a randomized trial in which patients were assigned to complete axillary lymph node clearance or a four-node sampling procedure. In that study, the patients with positive axillary lymph nodes underwent axillary irradiation. No differences in survival rates or patterns of relapse were found between the axillary clearance and axillary sampling groups.
The aim of this study was to compare the efficacy of the different surgical approaches of SLNB and FNS for predicting other nodal status first and then to examine the relationship between the sentinel lymph nodes (SLNs) and the four nodes (FNs) in operable breast cancer patients.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients and Tumor Characteristics
Between May 1997 and February 2001, all patients with an operable breast tumor that appeared malignant on fine-needle aspiration cytology or core-needle biopsy were asked to participate in this study. Patients were not enrolled when there was a large biopsy cavity, the clinical size of the tumor exceeded 5 cm in diameter, there was clinical evidence of axillary lymph node metastasis or a neoadjuvant chemotherapy had been administered. The protocol was approved by the local ethics committee and informed consent was obtained from all patients.
Surgery
For the first investigation, the identification of SLNs was carried out using radioactive tin colloids (Nihon Mediphysics, Tokyo, Japan), as reported previously (8,11). In brief, 1–3 ml of technetium-99m-labeled tin colloid (74–222 MBq) were injected subdermally and peritumorally, approximately 2 hours prior to surgery, with a concomitant dye injection of 5 ml of indigo carmine, to make the tin colloids run into SLNs by an increase in the interstitial pressure (12). The SLNs were identified as high radioactive nodes using an Auto Well Gamma System (Aloka, Tokyo, Japan) or the gamma probe "Navigator" (Auto Suture Japan, Tokyo, Japan).
The FNs obtained were palpable lymph nodes from the axilla, starting at the axillary tail and working upward. This surgery was performed by one surgeon (K.T.). The procedure was performed as Forrest et al. reported (13). The axillary tail was mobilized from the serratus anterior between the pectralis major and latissimus dorsi muscles up to the point where it merged with the lower axillary fat. Nodes were sought by inspection and palpation of the axillary tail and contiguous fat, particularly that adjacent to the vein emerging from the axillary tail. The surgeon was asked to identify and submit, separately, four nodes for histological examination.
In all patients for the identification of SLNs or FNs, a complete dissection of at least level I–II was performed after performing SLNB or FNS. All nodes were completely embedded for microscopic evaluation and stained with hematoxylin and eosin at the level of the hilus. The incidence of metastasis in SLNs and non-SLNs and that in FNs and non-FNs was compared.
For the second investigation, to compare SLNs and FNs, a retrospective analysis was carried out on all patients whose SLNs had been identified for the first investigation. According to the detailed information of all dissected lymph nodes, such as site and size, the retrospective FNs (rFNs) were chosen; these were four nodes large in size (>5 mm) from the lower part of the axilla. The relationship between SLNs and rFNs was classified into three categories: (i) rFNs that included SLNs, (ii) rFNs that partially included SLNs and (iii) no relationship. The comparison was carried out to elucidate the relationship between SLNs and FNs.
Statistical Analysis
Comparative analysis was performed by using either the t-test or the chi-squared test for patient characteristics. Differences were considered significant if the P value fell below 0.05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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A total of 206 patients were enrolled in this study. They were assigned to one of two groups according to the former investigation: the SLNB (n = 110) or the FNS (n = 98) group. The characteristics of each group are given in Table 1. No significant differences were observed in the characteristics between the two groups.
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Predictive Value of SLNs and FNs
SLNs were successfully identified in 108 (98%) of 110 patients. The 108 patients had a mean of 1.7 SLNs (range, 1–7) per patient. Three patients had SLNs at the axilla level I–II and other sites. No patient had SLNs located only outside the axilla. The nodal status of SLNs and non-SLNs is shown in Table 2. The SLNs were negative for cancer in 68 patients (64%), one of whom had at least one positive non-SLN (1.5% ‘skip’ metastasis). Therefore, the accuracy and sensitivity were 99 and 98%, respectively.
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In the FNS group, the mean number of FNs per axillary specimen was 4.0 (range, 2–7). The nodal status of FNs and non-FNs is listed in Table 3. FNS indicated two patients with metastasis in non-FNs (3.8% ‘skip’ metastasis) and its accuracy and sensitivity were 98 and 96%, respectively.
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Relationship Between SLNs and rFNs
In the SLN group, the four axillary lymph nodes per axillary specimen were retrospectively selected as rFNs. The nodal status of rFNs and non-rFNs is shown in Table 4. The relationship between SLNs and rFNs was as follows: (i) rFNs included SLNs in 79 patients (73%); (ii) rFNs partially included SLNs in 24 patients (22%); and (iii) no relationship was found in five patients (5%). In the ‘no relationship’ class, no skip metastases were indicated by SLNs or by rFNs: three patients in this class had no metastasis and two had metastatic nodes in SLNs and non-SLNs and in rFNs and non-rFNs.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Axillary lymph node status remains the single most important prognostic parameter and has therapeutic implications in patients with breast cancer. Surgical dissection of the axilla is commonly regarded as the standard procedure of axillary staging. Owing to the potential morbidity of unnecessary dissection, management of the axilla has become controversial.
SLNB, in which the first node to drain the tumor-bearing area is identified and excised, is being investigated as an alternative to the dissection of the entire axilla. It has been demonstrated in recent studies (5–8) that SLNB in breast cancer is feasible and safe. However, several problematic aspects of this method still require resolution (14,15), such as the occurrence of a false negative in frozen sections of the lymph nodes (6), the use of radioisotopes in some designated institutes and the costliness of the gamma probe.
An alternative treatment to axillary clearance is primary axillary radiotherapy, which produces results similar to those of axillary clearance (16–18). However, this technique gives no information of axillary status and induces a high morbidity comparable to that of surgical dissection (10).
FNS is a useful alternative to SLNB for such institutes, where there are some restrictions on the use of radioisotopes or applying frozen section examination. It was demonstrated in a report on a randomized trial that FNS is associated with no increase in axillary recurrence or mortality rate compared with routine axillary clearance and that patients who are found to be node-negative after this procedure need not undergo radiotherapy or axillary clearance.
Given the above findings, the aim of this study was to determine the comparative accuracy of SLNB and FNS for predicting axillary nodal involvement and the relationship between the two techniques.
Given that the accuracy/sensitivity of FNs was found to be comparable to that of SLNs in patients with the same characteristics, FNS represents a highly promising approach to the clinical management of patients.
One reason for the satisfactory accuracy of this method was speculated to be that, because the site of SLNs tends to be in the lower part of the axilla and the nodes are large in size (8), FNS, the aim of which is to obtain at least four palpable lymph nodes from the lowest axilla, can remove SLNs in most patients. In this study, this association was shown by rFNs on which postoperative dissection was carried out.
Currently, the diagnostic and therapeutic impact of the detection of extra-axillary SLN is still unclear. FNS can focus only on axillary nodes and thereby prevent unnecessary dissection of the axilla in FNs-negative patients. Further, axillary clearance in FNs-positive patients can be obtained subsequent to radiotherapy, in which regard this method is comparable to SLNB. Although FNS may have a higher morbidity and need more surgical skill to remove the vulnerable nodes than SLNB, it can be considered an alternative procedure and can be performed safely and easily in any institute.
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FOOTNOTES |
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+ For reprints and all correspondence: Kazuhiko Sato, Department of Surgery I, National Defense Medical College, 3–2 Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail: sato-k-a@mtg.biglobe.ne.jp
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Received February 25, 2001; accepted March 27, 2001.
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