Flyer

Archives in Cancer Research

  • ISSN: 2254-6081
  • Journal h-index: 14
  • Journal CiteScore: 3.77
  • Journal Impact Factor: 4.09
  • Average acceptance to publication time (5-7 days)
  • Average article processing time (30-45 days) Less than 5 volumes 30 days
    8 - 9 volumes 40 days
    10 and more volumes 45 days
Awards Nomination 20+ Million Readerbase
Indexed In
  • China National Knowledge Infrastructure (CNKI)
  • CiteFactor
  • OCLC- WorldCat
  • Publons
  • Geneva Foundation for Medical Education and Research
  • Euro Pub
  • Google Scholar
  • J-Gate
  • Secret Search Engine Labs
  • International Committee of Medical Journal Editors (ICMJE)
  • Zenodo
Share This Page

Research Article - (2021) Volume 0, Issue 0

The Management of Sentinel Lymph Node Biopsy in Breast Cancer

Victor Titirez1 and Roxana Elena Mirică2*

1Department of Surgery, Consultant Oncoplastic Breast Surgeon, Chesterfield Royal Hospital, UK

2Department of Medicine, Specialized in Abdominal Ultrasound, Associate Professor at University of Medicine and Pharmacy, Regina Maria Private Health Care Network, Romania

*Corresponding Author:
Roxana Elena Mirică
Department of Medicine
Specialized in Abdominal Ultrasound
Associate Professor at University of Medicine and Pharmacy
Regina Maria Private Health Care Network, Bucharest
Romania.
E-mail:
roxmirica@yahoo.com

Received Date: June 08, 2021; Accepted Date: June 23, 2021; Published Date: June 23, 2021

Citation: Titirez V, Mirica RE (2021) The Management of Sentinel Lymph Node Biopsy in Breast Cancer. Arch Can Res Vol.9 No.S4:1.

Visit for more related articles at Archives in Cancer Research

Abstract

Breast cancer is a public health issue due to its high incidence and mortality in advanced stages. As breast cancer is lymphophilic (the disease is spread mainly through the lymphatic system), axillary surgery remains essential in the treatment and staging of this condition. Sentinel lymph node biopsy has become the gold standard for axillary nodal staging, successfully replacing total axillary lymphadenectomy. This procedure has evolved significantly in the last 30 years and represents a topic of great relevance and interest. Certain issues related to the sentinel lymph node (identification techniques, indications and contraindications, the role of adjuvant therapy), will be highlighted in this paper.
 

Keywords

Breast Cancer; Sentinel Lymph Node Biopsy; Techniques of Sentinel Lymph Node Biopsy; Total Axillary Lymphadenectomy

Introduction

Breast cancer is the second leading cause of death worldwide in recent years [1]. Recently, the screening and therapeutic techniques performed for breast cancer have led to early detection of the disease, reduced complications and increased survival rates at 5 years [2]. Assessment of regional lymph node status in patients with this condition is particularly important for therapeutic and prognostic decisions [3]. Neoplastic dissemination is performed mainly by the lymphatic system at the level of the first lymph node (sentinel node) which drains the lymph from the tumour [4].

The term "sentinel node" was first introduced in 1951 by Gould during a parotidectomy [5]. In 1977, Cabanas adopted it for penile neoplasm [6]. In 1992, Donald Morton demonstrated the veracity of lymphatic dissemination of cutaneous malignant melanoma [7]. The identification of the sentinel node in breast cancer was performed in 1993 by Kreg, who used a radioactive tracer with a gamma camera [8], and in 1994, Giuliano did the same research using blue dyes at the John Wayne Oncology Institute [9].

The article aims to highlight the importance of the sentinel node in breast cancer.

Materials and Methods

Sentinel node versus total axillary lymphadenectomy

The sentinel nodes are defined as the first node or nodes that drains lymph from the breast and implicitly from the tumour, while also representing a prognostic marker (by the possibility of specifying the nature of regional nodes) for the 5-year survival rate and a factor in establishing the local and systemic therapeutic attitudes [2].

It is essential that patients receive an adequate pre-therapeutic assessment of the axillary lymphatic region. At the time of surgery, there are patients with positive sentinel lymph node who require completion axillary lymphadenectomy and those with a negative result for whom axillary lymphadenectomy is not required [10].

Sentinel lymph node biopsy was accepted as a less invasive axillary staging alternative than total axillary lymphadenectomy for those patients diagnosed in the early stages of the disease (pN0). The morbidity in these cases decreased significantly [2].

The results of the ACOSOGZ0011 study showed that completion axillary lymphadenectomy in situations where there are only 1-2 positive axillary sentinel nodes can be avoided in patients with less advanced breast cancer, with no significant differences in 10- year survival [11].

In the management of breast cancer, axillary lymphadenectomy was the gold standard for staging, but unwanted effects such as arm lymphedema accompanied by limited movement, skin sensitivity disorders and seroma formation led to its successful replacement by sentinel lymph node biopsy [2] (Table 1).

Indications Contraindications Special circumstances
Early stage breast cancer (T1, T2) and clinically negative axilla [12] or T3 and clinically negative axilla [13] The 2014 American Society of Clinical Oncology and 2010 International Expert Panel Guidelines recommended that sentinel lymph node biopsy not be performed in patients with inflammatory breast cancer (T4d) [14] or breast cancer with dissemination to the skin and chest wall; in these conditions axillary lymphadenectomy is performed [10] Neoadjuvant chemotherapy
<3 invaded lymph nodes on sentinel lymph node biopsy in patients with lumpectomy followed by irradiation of the whole breast [10]
Mastectomy performed for extensive (ductal carcinoma in situ) DCIS Multicenter disorders
DCIS with clinical suspicion of an invasive condition, including tumor size> 5 cm [4]
DCIS with lumpectomy, with subsequent identification of an invasive form of the disease [10] History of breast and axillary surgery [14]
Negative axillary lymph nodes after neoadjuvant therapy (c N0) [10]
In case of conversion of positive N1 tumours to N0, neoadjuvant post-therapy [10] Pregnancy: the only dye accepted as safe for the foetus  in sentinel lymph node biopsy is methylene blue [15]

Table 1: Indications and contraindications for performing sentinel lymph node biopsy.

The indications for total axillary lymphadenectomy are:

•≥ 3 lymph nodes invaded at sentinel node biopsy

•1, 2 lymph nodes metastasized to sentinel node biopsy,but without irradiation of the entire breast [10].

Research conducted by the Yale School of Public Health shows that elderly patients diagnosed with early breast cancer (ductal carcinoma in situ) do not benefit from excision sentinel lymph node biopsy, because it reduces neither the risk of mortality from the disease nor the development of a more aggressive form thereof [16]. A prospective study presented at a virtual symposium in December 2020 (San Antonio Breast Cancer) showed that patients over the age of 70, who were estrogen-receptor positive and HER 2 negative, and who were being administered hormone therapy, showed a significantly increased survival rate [17]. NICE guidelines recommend that sentinel lymph node biopsy should not be routinely performed in patients diagnosed with ductal carcinoma in situ or candidates for lumpectomy. It should only be proposed if they are considered to be at increased risk of developing an invasive form of the disease [18] or when they require radical mastectomy [19].

The NICE guidelines recommend the following:

1.Do not perform adjuvant axillary radiotherapy after complete axillary lymphadenectomy.

2.Do not perform axillary or supraclavicular radiotherapy in patients with early breast cancer with a negative sentinel lymph node.

3.Do not administer Paclitaxel as adjuvant therapy to patients with positive sentinel lymph node breast cancer.

4.Patients whose sentinel lymph node has isolated malignant cells (ITC) should be considered to have a negative sentinel lymph node (Table 2).

Before After
The most accurate way to assess the status of the axillary lymph nodes, allowing the practice of selective axillary surgery [20] Decreased sentinel lymph node accuracy by inadequate response (primary tumour and metastatic lymph nodes responding to chemotherapy produce reactive fibrosis-like changes that influence lymph drainage pattern [21]
May show an increased rate of false-negative results after neoadjuvant chemotherapy according to The SENTINEL NeoAdjuvant Study [2] It can be performed in patients with proven axillary lymph node metastases before starting neoadjuvant therapy [22]
In cases of extensive breast cancer [23]

Table 2: Conditions for sentinel lymph node biopsy before and after neoadjuvant therapy.

Techniques used in sentinel lymph node biopsy

Sentinel lymph node biopsy is performed by injecting 1 or 2 tracers (recommended technique) at the breast parenchyma or subareolar plexus. These tracers enter the lymphatic system and are transported to the sentinel lymph node that takes the lymph from the tumour [24].

The sentinel lymph ganglion can be identified using several techniques and different substances, such as: vital dyes, radioactive tracers or the combination of the 2 methods.

When sentinel node is identified with vital dyes, the most commonly used are Isosulfan Blue, Fluorescein and Patent Bleu V [25], which is injected at the periphery of the tumour or in the subareolar plexus. Chagpar has shown that injection at the subareolar and periareolar regions leads to better sentinel lymph node identification than by peritumoral injection [26]. It is important not to inject directly into the tumour, the procedure involves injecting the substance and massaging the area in order to promote faster drainage [27]. Isosulfan blue is associated with anaphylactic-type side effects [24] and can be replaced by methylene blue, which also produces certain (milder) adverse reaction, such as induration and local pain-associated erythema [28].

Discussion

The radioactive tracer consists of a radioactive isotope that is attached to a colloidal substance and is injected preoperatively at the periphery of the tumour, intradermally or in the subareolar plexus [29]. 99 mTc is the most used radioactive isotope in the sentinel lymph node biopsy technique, being efficient and safe. In the USA, sulphur colloid marked with 99 mTc is used, and in Europe nanocolloid human serum albumin marked with 99 mTc is used, the latter having a rapid resorption and migration from the injection site into the lymphatic network and a high degree of retention in the sentinel lymph node [29]. In recent years, new radiocolloids, which are much more efficient than the current ones, have occurred:

• 99 mTc tilmanocept has a high degree of localisation, rapid migration into the lymphatic network and no contraindications or significant adverse reactions [30,31].

• 99 mTc rituximab provides very clear images with high accuracy, sensitivity and specificity [25].

The current gold standard for sentinel lymph node biopsy is the concomitant use of vital dyes and radioactive tracer to identify it, ensuring a higher identification rate and a much lower rate of false-negative results (according to the American Society of Clinical Oncology) [32].

Lymphoscintigraphy is performed using the gamma camera to identify the area with increased radioactivity “hot spots” [33] (Table 3).

  Advantages Disadvantages
Indo Cyanine Green (ICG)
  • Injected directly into the breast (subareolar) [33]
  • Real time visualisation
  • Can detect a large number of lymph nodes
  • Safe method
  • Does not require nuclear medicine department [25]
  • Without severe side effects
  • Reduced false-negative results [34]
  • At a concentration <5 mg / ml, increases sensitivity [25]
  • It cannot be used in patients with iodine allergy
  • It cannot detect lymph nodes located> 1 cm deep
SentiMag system with SPIO (Super Paramagnetic Iron Oxide nanoparticles)
  • Avoid the use of radioisotopes
  • It is a much more efficient alternative to the radioactive tracer [25]
  • It is injected directly into the breast, providing an ultra-sensitive detection of the magnetic tracer
  • Non-invasive
  • Does not require a nuclear medicine department , so surgeons have control of the procedure in sentinel lymph node biopsy
  • No major allergic reactions [25]
  • In case of involvement of invaded node, SPIO are deposited only in the unaffected areas of the lymph node [35]
  • Possible interference of the surgical instrument with the ferromagnetic signal
  • Does not detect deep lymph nodes [36]
  • May not be used in patients with hypersensitivity to iron, dextran or peacemaker compounds and in those undergoing sentinel node biopsy prior to chemotherapy [37]
Contrast Enhanced Ultrasound (CEUS) with microbubbles
  • "Real time"visualisation
  • Does not require a nuclear medicine department
  • Requires only an ultrasound and a contrast agent
  • No side effects
  • Non-invasive
  • The microbubbles are based on the method of dispersion with sulphur hexafluoride gas
  • Injected periareolarly
  • The lymphatic network of the breast is visualised by ultrasonography and then identified and biopsied the sentinel lymph node [39]
  • It is not a very fast method
  • Dependent on an operator
  • Some studies have shown that the combined technique (vital dyes and radiotracer) is more effective than ceus on sentinel lymph node identification rate [38]

Table 3: New techniques used in sentinel node biopsy.

Conclusion

The status of the axillary lymph nodes is one of the most important prognostic factors in breast cancer patients. In early stages of breast cancer (T1, T2) and clinically negative axilla, the current standard is the identification and biopsy of the sentinel lymph node, which, in case of a negative result, avoids the total axillary lymphadenectomy that is performed if the status of the sentinel lymph node is positive (considering that it reflects the condition of the other axillary nodes), or if the stage of the disease is more advanced (T3, dimensions exceeding 5 cm).

In the case of Ductal Carcinoma In Situ (DCIS), sentinel lymph node biopsy is performed only if mastectomy is recommended. Special circumstances such as pregnancy, neoadjuvant chemotherapy, a history of surgery on the breast or axilla are not a contraindication for the identification and biopsy of the sentinel lymph node, while inflammatory breast cancer is an absolute contraindication.

In case of a recurrence of the breast neoplasm or a procedure performed at the axillary level in the background, it is recommended to perform lymphoscintigraphy with nanocolloid human serum albumin marked with Tc99 or sulphur colloid, which has proven very effective for the sentinel lymph node technique.

The identification of the sentinel lymph node can be done using vital dyes (isosulfan blue, fluorescein, patent blue V), radioactive tracers (radioactive isotope fixed on a colloidal substance) or the combination of the 2 methods. The new techniques used (green indocyanine, superparamagnetic iron oxide nanoparticles and contrast ultrasound using microbubble as a contrast agent) have proven to be safe and feasible, with high specificity and sensitivity, so that surgeons can perform the interventions, independent of nuclear medicine departments.

Acknowledgements

Not applicable.

Funding

No funding was received.

Conflict of Interest

The authors declare that they have no conflict of interest.

38351

References

  1. DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, et al. (2019) Breast cancer statistics, 2019. CA Cancer J Clin 69:438–451.
  2. Marta SN, Mastika NDAH, Irawan H (2020) A Review and Current Update on Sentinel Lymph Node Biopsy of Breast Cancer. Open Access Maced J Med Sci 8(F):78-83.
  3. Gerber B, Heintze K, Stubert J, Dieterich M, Hartmann S, et al. (2011) Axillary lymph node dissection in early-stage invasive breast cancer: Is it still standard today? Breast Cancer Res Treat 128(3):613–624.
  4. Li X, Chen S, Duan Y, Guo H, Jiang L, et al. (2020) Identification and preservation of stained non sentinel lymph nodes in breast cancer. Oncology Letters. 20(6): 373-378.
  5. Gould EA, Winship T, Philbin PH, Kerr HH (1960) Observations on a sentinel node in cancer of the parotid. Cancer 13:77-78.
  6. Wespes E, Simon J, Schulman C (1986) Cabanas approach: Is sentinel lymph node biopsy reliable for staging penile carcinoma? Urology 28(4):278-9.
  7. Cochran AJ, Wen D, Morton DL (1992) Management of the regional lymph nodes in patients with cutaneous malignant melanoma. World J Surg 16(2):214-21.
  8. Veronesi U, Adamus J, Bandiera DC, Brennhovd IO, Caceres E, et al. (1977) Inefficacy of immediate node dissection in stage 1 melanoma of the limbs. N Engl J Med 297(12):627-30.
  9. Giuliano AE, Kirgan DM, Guenther JM, Morton DL (1994) Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 220(3):391-8.
  10. Harlow SP, Weaver DL (2020) Overview of sentinel lymph node biopsy in breast cancer.
  11. Giuliano AE, Ballman KV, Mccall L, Beitsch PD, Brennan MB, et al. (2017) 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 318(10):918-26.
  12. William G, Benjamin A, Jame A, Rebecca AFT, Doreen A, et al. (2020) NCCN Clinical Practice Guidelines in Oncology, (NCCN Guidelines). Breast Cancer. Version 3. J Natl Compr Canc Netw 18(4):452-478.
  13. Chung MH, Ye W, Giuliano AE (2001) Role for sentinel lymph node dissection in the management of large (> or = 5 cm) invasive breast cancer. Ann Surg Oncol 8:688-692.
  14. Lyman GH, Temin S, Edge SB, Newman LA, Turner RR, et al. (2014) Sentinel lymph node biopsy for patients with early-stage breast cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 32(13):1365-83.
  15. Cragan JD (1999) Teratogen update: methylene blue. Teratology 60(1):42-48.
  16. Colin Poitras (2019) Sentinel lymph node biopsy has no benefits for stage zero breast cancer. Med Dev Netw.
  17. SABCS 2020: Sentinel Node Biopsy Can Be Omitted for Select Low-Risk Elderly Breast Cancer Patients. Metastatic Breast Cancer, 2020.
  18. NICE guidance. Sentinel lymph node biopsy slnb routinely in patients with a preoperative diagnosis of ductal carcinoma in situ dcis, 2009.
  19. Virnig BA, Tuttle TM, Shamliyan T, Kane RL (2010) Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst 102:170-8.
  20. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, et al. (2013) Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): A prospective, multicentre cohort study. Lancet Oncol. 14(7):609-18.
  21. Carolien H.M van Deurzen CH, Vriens BP, Tjan-Heijnen VC, van der Wall E, Albregts M, et al. (2009) Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer patients: A systematic review. Eur J Cancer 45(18):3124-30.
  22. Enokido K, Watanabe C, Nakamura S, Ogiya A, Osako T, et al. (2016) Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with an initial diagnosis of cytology-proven lymph node-positive breast cancer. Clin Breast Cancer 16(4):299-304.
  23. Classe JM, Bordes V, Campion L, Mignotte H, Dravet F, et al. (2009) Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: Results of ganglion sentinelle et chimiotherapie neoadjuvante, a french prospective multicentric study. J Clin Oncol 27(5):726-32.
  24. Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, et al. (2007) Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol 8(10):881-8.
  25. Ferrucci M, Franceschini G, Douek M (2018) New techniques for sentinel node biopsy in breast cancer. Translational Cancer Research 7(3).
  26. Chagpar AB, Martin RC, Scoggins CR, Carlson DJ, Laidley AL, El-Eid SE, et al. (2005) Factors predicting failure to identify a sentinel lymph node in breast cancer. Surgery 138:56-63.
  27. Harlow SP (2019) Sentinel lymph node biopsy in breast cancer: Techniques.
  28. Bleicher RJ, Kloth DD, Robinson D, Axelrod P (2009) Inflammatory cutaneous adverse effects of methylene blue dye injection for lymphatic mapping/sentinel lymphadenectomy. J Surg Oncol 99(6):356-60.
  29. McMasters KM, Wong SL, Martin RC 2nd, Chao C, Tuttle TM, et al. Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study. Ann Surg 233(5):676-87.
  30. Kim CK, Zukotynski KA (2017) Desirable properties of radiopharmaceuticals for sentinel node mapping in patients with breast cancer given the paradigm shift in patient management. Clin Nucl Med 42(4):275-279.
  31. Surasi DS, O'Malley J, Bhambhvani P (2015) 99mTc-Tilmanocept: a novel molecular agent for lymphatic mapping and sentinel lymph node localization. J Nucl Med Technol 43(2):87-91
  32. Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, et al. (2005) American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early stage breast cancer. J Clin Oncol 23(30):7703-20.
  33. McMasters KM, Wong SL, Tuttle TM, Carlson DJ, Brown CM, et al. (2000) Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes. Ann Surg 231(5):724-31.
  34. Tong M, Guo W, Gao W (2014) Use of fluorescence imaging in combination with patent blue dye versus patent blue dye alone in sentinel lymph node biopsy in breast cancer. J Breast Cancer 17(3):250-255.
  35. Johnson L, Pinder SE, Douek M (2013) Deposition of superparamagnetic iron-oxide nanoparticles in axillary sentinel lymph nodes following subcutaneous injection. Histopathology 62(3):481-6.
  36. Anninga B, White SH, Moncrieff M, Dziewulski P, L C Geh J, et al. (2016) MELAMAG Multicentre Trialists Group. Magnetic technique for sentinel lymph node biopsy in melanoma: the MELAMAG Trial. Ann Surg Oncol 23(6):2070-8.
  37. Huizing E, Anninga B, Young P, Monypenny I, Craggs MH et al. (2015) Analysis of void artifacts in post-operative breast MRI due to residual SPIO after magnetic SLNB in SentiMAG Trial participants. Eur J Surg Oncol 41(S18): 74757546.
  38. Ahmed M, Purushotham AD, Douek M (2014) Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review. Lancet Oncol 15(8):e351-62.
  39. Cox K, Sever A, Jones S, Weeks J, Mills P, et al. (2013) Validation of a technique using microbubbles and contrast enhanced ultrasound (CEUS) to biopsy sentinel lymph nodes (SLN) in pre-operative breast cancer patients with a normal grey-scale axillary ultrasound. Eur J Surg Oncol 39(7):760-765.