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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 6  |  Page : 1265-1268

Diagnostic accuracy of sentinel lymph node biopsy in determining the axillary lymph node metastasis


1 Department of General Surgery, Goztepe Education and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
2 Department of Pathology, Goztepe Education and Research Hospital, Istanbul Medeniyet University, Istanbul, Turkey
3 Department of Biostatistics and Medical Informatics, Istanbul Medeniyet University, Istanbul, Turkey

Date of Submission16-Dec-2019
Date of Decision07-Apr-2020
Date of Acceptance18-Jun-2020
Date of Web Publication18-Dec-2020

Correspondence Address:
Ozlem Okur
Egitim Mahallesi Dr. Erkin Cad. Goztepe Egitim Arastirma Hastanesi, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1122_19

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 > Abstract 


Background: Sentinel lymph node biopsy (SLNB) is accepted as the standard procedure to determine the axillary lymph node metastasis in breast cancer at early stage. However, in many cases with sentinel lymph node positivity, the axilla does not contain any tumor cells. As a result, the accuracy of SLNB to predict axillary lymph node metastasis must be evaluated.
Patients and Methods: Thousand hundred and fourteen women operated for breast cancer were retrospectively examined. Breast cancer patients without axillary metastasis on clinical examination who had undergone SLNB were included in the study. Sentinel lymph node positivity and axillary lymph node positivity were compared.
Results: Among 1114 women operated for breast cancer, 230 were clinically node negative preoperatively and undergone SLNB. Eighty-three (36%) of the patients were SLNB positive and undergone axillary dissection. Forty-three (51.8%) of them had tumor positive axillary lymph nodes and 40 (48.2%) of them had tumor negative axillary lymph nodes.
Interpretation: In 48.2% of the patients, positive sentinel lymph node does not demonstrate a positive axilla. This finding supports sparing axillary dissection in patients with favorable prognostic factors even if the sentinel lymph node is found to be positive.
Conclusion: Axillary lymph node dissection(ALND) may be spared even if there are macrometastatic sentinel lymph nodes in patients with favorable tumor types who will undergo breast-conserving surgery.

Keywords: Axillary lymph node metastasis, early breast cancer, sentinel lymph nodes


How to cite this article:
Okur O, Sagiroglu J, Kir G, Bulut N, Alimoglu O. Diagnostic accuracy of sentinel lymph node biopsy in determining the axillary lymph node metastasis. J Can Res Ther 2020;16:1265-8

How to cite this URL:
Okur O, Sagiroglu J, Kir G, Bulut N, Alimoglu O. Diagnostic accuracy of sentinel lymph node biopsy in determining the axillary lymph node metastasis. J Can Res Ther [serial online] 2020 [cited 2021 Dec 4];16:1265-8. Available from: https://www.cancerjournal.net/text.asp?2020/16/6/1265/303887




 > Introduction Top


There are two types of lymphatic vessels in the breast: superficial and deep lymphatics. Superficial lymphatics drain to the deep lymphatics and lymph from the deep lymphatics flows toward the internal mammarian and axillary lymph nodes. About 3% of the lymph drain to the internal mammary nodes and the rest (97%) of the lymph drain to the axillary lymph nodes.[1] Lymphatic mapping and sentinel was first reported in 1977 by Cabanas for penile cancer. He studied one hundred cases using lymphangiograms, anatomic dissection, and microscopic evaluation. He demonstrated the existence of specific lymph node center called sentinel lymph node which is the first site of metastasis from penile carcinoma. Lymphatics never drained into the iliac or inguinal and femoral lymph nodes before they had drained into sentinel lymph nodes.[2] Most neoplasms have the ability to metastasize via the lymphatics, and therefore, in oncologic operations, the primary tumor and the draining lymphatics are removed en bloc. This type of surgery is carried out when the lymph nodes draining the primary tumor site are adjacent to tumor bed as colorectal cancers and gastric cancers. For tumors in which regional lymph nodes not immediately adjacent to the tumor (e.g. melanomas and breast cancer), lymph node surgery is performed through a separate incision.[3]

For patients who have early breast cancer and are clinically node negative on physical and radiologic studies, the sentinel lymph node is used to determine the axillary lymph node metastasis.[4]

Axillary lymph node metastasis progresses regularly from the first to the second, then to the third lymph node.[5] If the sentinel lymph node is clear of tumor cells, then axillary lymph nodes are accepted as clear. If SLN contains tumor cells, axillary dissection is recommended under certain circumstances discussed below. In our study, we evaluated the value of sentinel lymph node biopsy (SLNB) in determining the positive lymph nodes in the axilla. We know that negative SLNB means negative axilla. We analyzed if positive sentinel nodes can predict positive axillary lymph nodes.


 > Patients and Methods Top


Patients

The study was approved by the ethics committee. It was a single-center retrospective study. We studied 230 patients with operable breast carcinoma from January 2007 to January 2019. Patients with c T1–T3 and c N0 patients were included in the study. We excluded patients with clinically positive lymph nodes.

The youngest patient was 29 years old and the oldest patient was 84 (mean 54.96 ± 11.88) years old. The tumor size, measured on pathological sectioning, ranged from 0.7 cm to 12.5 cm. Characteristics of 83 patients are summarized in [Table 1].
Table 1: Characteristics of 83 patients

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Surgery

Sentinel lymph node dissection is carried out with the aid of blue dye (isosulfan blue or methylene blue). Five milliliter of blue dye is injected in the subareolar plexus. After 5 min of breast massage toward the axilla, a 3–4 cm incision is made in the lower axilla just below the hairline. After dissecting through subcutaneous tissue, the axillary fascia is dissected and blue lymphatic channels are followed. Following these channels leads to sentinel lymph node.[4],[6]

The node is sent to the pathology laboratory for frozen section analysis. If macrometastasis, i.e., =2 mm metastasis, is found, then SLNB is followed by axillary dissection. In case of negative SNLB or micrometastasis, axillary lymph node dissection (ALND) is spared.

Pathological examination

Sentinel node frozen section examination

The size of the node or nodes was recorded. Each node was thinly sliced along the long axis of the node at 2 mm, and all slices were submitted for frozen section examination. At least one representative hematoxylin-and-eosin (H and E) level was examined.

Permanent examination of negative sentinel node

After the frozen section examination, all slices of the node of nodes were submitted for tissue processing. At least 10 representative H and E levels were examined. Immunohistochemical study (pancytokeratin) was performed to the second and eighth levels. Size of metastases and the presence of extranodal tumor invasion were recorded. Only the largest contiguous focus of tumor in the node evaluation was used for classification.

Statistical analysis

The purpose of our study is to find out the percentage of patients with axillary lymph node metastasis, whose sentinel lymph node is positive. We studied 83 patients having a positive sentinel node. The data were calculated as mean ± standard deviation, numbers, and % frequencies. The relation between axilla(+, -) = axillary lymph node involvement, tumor size, hormone receptor status, cERB2, Ki 67, and SLNB numbers was calculated using Chi-square or Fischer's exact test, and the relation between sentinel lymph node numbers was calculated using Mann–Whitney U-test. The Pearson chi square test results were shown by “%,” and Mann–Whitney-U test results are shown by “Min-Max.” Statistically, meaningful value is accepted as P < 0.05, and the data were calculated using IBM Corp., Released 2013, IBM SPSS for Windows, version 22.0 (Armonk, NY: IBM Corp,USA).


 > Results Top


Between January 2007 and January 2019, 1114 patients underwent breast cancer surgery. Two hundred and thirty of them who had clinically negative axilla underwent SLNB. Eighty-three patients were SLNB+ and underwent ALND. The aim of the study was to determine the accuracy of SLNB in predicting the presence of axillary lymph node metastasis. Forty patients (48.2%) had a negative axilla and 43 patients (51.8%) were positive for axillary metastasis. The age of the patients ranged between 29and 84 years (mean: 54.96 ± 11.88). The pathology of breast cancer was invasive ductal carcinoma in 70 patients. Eight patients had lobular carcinoma, four patients had mucinous carcinoma, and one patient had carcinosarcoma. The smallest tumor diameter was 0.7 cm and the largest tumor size was 12.5 cm. Tumor size was <2 cm in 26 (31.3%) patients and =2 cm in 57 (68.7%) patients. Ki-67 proliferation index was <7% in 24 (31.6%) patients and =7 in 52 (68.4%) patients. 10 patients were hormone negative and 73 patients were hormone positive. These findings are summarized in [Table 2].
Table 2: Patient characteristics and axillary lymph node involvement

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 > Discussion Top


Breast cancer prognosis depends on two factors: tumor size and axillary lymph node involvement. These two important factors act as independent but additive parameters. Five-year survival rate varies from 45.5% for tumors >5 cm with positive axilla to 96.3% for tumors <2 cm with negative axilla.[5]

Breast cancer treatment is tending to be less invasive and more targeted. The acceptable surgical margin is “no ink on tumor” for both invasive breast carcinoma and ductal carcinoma in situ. Surgery of the axilla is also being questioned. ALND can be omitted in patients with one or two macrometastatic lymph nodes if postoperative radiotherapy is planned.[6]

Axillary lymph node involvement is important in postoperative treatment planning and follow-up. In the past decades, ALND is decreasing progressively. Sentinel lymph node sampling is used instead of ALND in early-stage breast cancer patients without clinical axillary involvement.[7],[8]

Buscombe et al. explained procedural guidelines to detect sentinel lymph node in breast cancer. Both radiopharmaceuticals and blue dye are used.[9] Although sentinel lymph node is identified using both radioisotope tracer and isosulfan blue, it can be identified using isosulfan blue alone. Brahma studied 96 patients and the identification rate of sentinel lymph node was 91.7%.[10] Özdemir studied 32 patients and the SLN detection rate was 94%.[11] Ang Ch studied 610 patients and the detection rate of SLN was 98%.[12] ALMANAC trial studied 842 patients to detect false-negative rates of sentinel lymph node. Patients with clinically node-negative breast cancer underwent SLNB following the usage of radiopharmaceutical 99m Tc albümin and Patent blue V dye. Sentinel lymph node was identified in 803 (96.1%) of 836 cases. There were 19 false negatives, which resulted in sensitivity of 263/282 (93.3%) and accuracy of 782/803 (97.6%), The SLNs were successfully identified by the blue dye in 698 patients (85.6%), by radioisotope in 698 patients (85.6%), and by the combination of blue dye and radioisotope in 782/815 patients (96.0%). False-negative rate was 10.1% when one SLN was removed and 1.1% when multiple SLNs (=3) were removed (P: 0.01).[13]

Weaver DL studied 3887 patients and in 15.9%, there were occult metastases. Overall survival (P: 0.03), disease-free survival (P: 0.02), and distant disease-free interval (P: 0.04) were significantly different in between two groups, but no statistically significant difference was detected in 5-year survival rates between the two groups; 94.6% in group with occult metastasis and 95.8% in group without metastasis.[14] ALMANAC trial, which is the first large randomized controlled trial that compared SLNB with standard axillary treatment in patients having early breast cancer, studied 829 patients. The trial studied the quality of life over 18 months of postsurgical period. Sentinel group recovered more quickly and had less arm swelling (P = 0.002) and less numbness (P < 0.001). The findings supported SLNB in early breast cancer.[15] IBCSG trial 23-01, phase 3 randomized controlled trial, studied disease-free survival between patients who underwent SLNB and axillary dissection. The patients in this study had tumors <5 cm and were clinically node negative and had one or more mictometastatic (=2 mm) SLN. Four hundred and sixty-five patients were randomly assigned to axillary dissection group and 469 patients to nonaxillary dissection group. After the patients followed up of 5 years, they recorded disease-free survival in 69 (87.8%) patients in axillary dissection group and 55 (84.4%) patients in nonaxillary dissection group (P = 0.16). The study concluded that axillary dissection could be avoided in patients with limited lymph node involvement.[16]

ALND can be spared in patients who have clear sentinel lymph nodes or limited involvement (i.e., isolated tumor cells or micrometastasis?).[7],[8] Negative sentinel lymph node reliably demonstrates negative axilla.[4] However, in many cases with macrometastatic (>2 mm) SLNB, the axillary lymph nodes are also negative. We designed this study to evaluate the diagnostic accuracy of sentinel lymph node positivity in determining the axillary lymph node metastasis. We found that among 230 patients who had undergone sentinel lymph node sampling, 83 (36%) was positive which is the similar with 35.5% found in the study of Veronesi et al.[17] Of these 83 SLNB-positive patients, 48.2% had tumor negative axilla which is higher than 39.5% found in the study of Veronesi et al.[4] According to the ASCO guidelines, patients without SLN metastasis should not receive ALND. Patients with 1 or 2 sentinel lymph node positivity who are going to have breast-conserving surgery with whole-breast radiotherapy should not undergo ALND.[18]

ACOSOG Z0011 trial compared SLNB alone with ALND in women with T1/T2 tumors, <3 positive sentinel lymph nodes who will undergo breast-conserving surgery, and whole-breast radiation. There was no difference in local recurrence, disease-free survival, or overall survival between these two groups.[19]

Although the National Comprehensive Cancer Network (NCCN) guidelines for breast cancer, American College of Surgeons Oncology Group (ACOSOG) Z0011 trial, and American Society of Clinical Oncology (ASCO) guidelines include SLN-positive patients having T1 and T2 breast cancer to avoid ALND, our study included 10 patients with T3 tumor. Three of ten patients had clear axilla and seven of ten patients had metastatic ALN. Despite of this inclusion, we still had 48.2% tumor negative axillary lymph nodes in patients who had macrometastatic SLN. [20,21]


 > Conclusion Top


ALND may be spared even if there are macrometastatic sentinel lymph nodes in patients with favorable tumor types who will undergo breast-conserving surgery.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Sabel Michael S. Anatomy and phsiology of breast. In: Fletcher Judith LM, editor. Essentials of Breast Surgery. 1st ed. Philadelphia: Mosby Elsevier; 2009. p. 12.  Back to cited text no. 1
    
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Hunt KK, Robertson JF, Bland KI. The breast. In: Brunicardi FC, editor. Schwartz's Principles of Surgery. 10th ed. E Book: McGraw-Hill Education; 2015. p. 545-6.  Back to cited text no. 4
    
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Veronesi U, Paganelli G, Galimberti V, Viale G, Zurrida S, Bedoni M, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997;349:1864-7.  Back to cited text no. 5
    
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Sabel Michael S. Regional management of breast cancer. In: Fletcher Judith LM, editor. Essentials of Breast Surgery. 1st ed. Philadelphia: Mosby Elsevier; 2009. p. 188.  Back to cited text no. 6
    
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Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer 1989;63:181-7.  Back to cited text no. 7
    
8.
Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies–improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol 2015;26:1533-46.  Back to cited text no. 8
    
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van der Noordaa ME, Vrancken Peeters MT, Rutgers EJ. The intraoperative assessment of sentinel nodes-Standards and controversies. Breast 2017;34 Suppl 1:S64-9.  Back to cited text no. 9
    
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Esposito E, Di Micco R, Gentilini OD. Sentinel node biopsy in early breast cancer. A review on recent and ongoing randomized trials. Breast 2017;36:14-9.  Back to cited text no. 10
    
11.
Buscombe J, Paganelli G, Burak ZE, Waddington W, Maublant J, Prats E, et al. Sentinel node in breast cancer procedural guidelines. Eur J Nucl Med Mol Imaging 2007;34:2154-9.  Back to cited text no. 11
    
12.
Brahma B, Putri RI, Karsono R, Andinata B, Gautama W, Sari L, et al. The predictive value of methylene blue dye as a single technique in breast cancer sentinel node biopsy: A study from Dharmais Cancer Hospital. World J Surg Oncol 2017;15:41.  Back to cited text no. 12
    
13.
Ozdemir A, Mayir B, Demirbakan K, Oygur N. Efficacy of methylene blue in sentinel lymph node biopsy for early breast cancer. J Breast Health 2014;10:88-91.  Back to cited text no. 13
    
14.
Ang CH, Tan MY, Teo C, Seah DW, Chen JC, Chan MY, et al. Blue dye is sufficient for sentinel lymph node biopsy in breast cancer. Br J Surg 2014;101:383-9.  Back to cited text no. 14
    
15.
Goyal A, Newcombe RG, Chhabra A, Mansel RE; ALMANAC Trialists Group. Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer–results of the ALMANAC validation phase. Breast Cancer Res Treat 2006;99:203-8.  Back to cited text no. 15
    
16.
Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, et al. Effect of occult metastases on survival in node-negative breast cancer. N Engl J Med 2011;364:412-21.  Back to cited text no. 16
    
17.
Fleissig A, Fallowfield LJ, Langridge CI, Johnson L, Newcombe RG, Dixon JM, et al. Post-operative arm morbidity and quality of life. Results of the ALMANAC randomised trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer. Breast Cancer Res Treat 2006;95:279-93.  Back to cited text no. 17
    
18.
Galimberti V, Cole BF, Zurrida S, Viale G, Luini A, Veronesi P, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): A phase 3 randomised controlled trial. Lancet Oncol 2013;14:297-305.  Back to cited text no. 18
    
19.
Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003;349:546-53.  Back to cited text no. 19
    
20.
Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, Weaver DL, et al. Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2014;32:1365-83.  Back to cited text no. 20
    
21.
Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, et al. Effect of axillary dissection vs. no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA 2017;318:918-26.  Back to cited text no. 21
    



 
 
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  [Table 1], [Table 2]



 

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