ReviewEvolution in sentinel lymph node biopsy in breast cancer
Introduction
Axillary staging is an important component of the surgical procedure performed in patients with breast cancer. This was initially performed as axillary lymph node dissection (ALND). This procedure has changed since randomized trials showed that sentinel lymph node biopsy (SLNB) reflects the overall axillary lymph node (ALN) status. No difference in regional control, disease free survival (DFS) and overall survival (OS) was found between SLNB and ALND in patients with clinically negative nodes (Veronesi et al., 2006a, Krag et al., 2010). Moreover the SLNB group experienced an improved quality of life (QoL) and upper extremity function (Mansel et al., 2006, Ashikaga et al., 2010). These results made SLNB the standard of care for ALN staging in patients with early breast cancer and clinically negative ALNs (Lyman et al., 2005). In about 75% of the patients who undergo SLNB, this biopsy does not contain tumor cells (Krag et al., 2007). There is now increasing interest, based on “Primum non nocere”, in properly selecting patients with a low probability of ALN metastasis and therefore might not even require a SLNB (Gentilini and Veronesi, 2012).
Neoadjuvant chemotherapy (NAC) is offered to patients with locally advanced diseases in order to downstage the tumor and is increasingly being used for large operable tumors for decreasing the extent of surgery needed (Senkus et al., 2015). ALND has been standard treatment of the axilla after NAC for many years (Lyman et al., 2005). However, around 40% of those patients with a clinically or biopsy-proven positive lymph node get a histopathologically complete response (pCR) after NAC (Fisher et al., 1997) and rates increased to more than 70% with using of anti-HER2 therapy (Dominici et al., 2010). Moreover, axillary staging after NAC has been reported to be more meaningful in predicting locoregional recurrence than the axillary staging before NAC, and therefore can be used to guide adjuvant locoregional treatment (Mamounas et al., 2012). These data supports the application of SLNB after NAC in order to reduce the extent of axillary surgery without compromising the prognostic and predictive value of axillary staging. Argument against the application of SLNB after NAC is that the lymphatic drainage alteration after NAC could decrease the SLN identification rate and increase the false-negative rate (FNR) (Jatoi et al., 2016). However, increasing data showed that the SLN identification rate and FNR were comparable between SLNB before and after NAC in patients with pretreatment clinically negative nodes. In general, the SLN identification rate and FNR of SLNB after NAC are less satisfactory in patients with pretreatment positive nodes. However, in subset of patients the accuracy of SLNB in this setting has been reported to be similar with that in patients without NAC (Boughey et al., 2013, Kuehn et al., 2013, Boileau et al., 2015).
For optimal SLN detection, tracers are applied. The current standard tracers have limitations. For example, the logistic and legislative issues of using a radioisotope limit the application of radioactive tracer method in many countries/regions in the world. In several developing countries, including China (Li et al., 2015), only blue dye is available for SLNB. Blue dye carries a risk of allergic reactions in around 1% of the patients (Cady, 2002) for the whole spectrum and 0.2% (Krag et al., 2007) for severe reactions. Besides, the performance of SLNB using a blue dye is highly dependent on a surgeons’ experience (Ang et al., 2014), lacking the guidance of devices such as a gamma probe used in radioisotope guided SLNB, and relies, obviously, on visual detection of the SLN (Fig. 1). The above-mentioned potential limitations of both standard tracers have led to the development of alternative methods for SLNB. Data from studies on indocyanine green (ICG) optical imaging or superparamagnetic iron oxide (SPIO) guided SLNB in early breast cancer is encouraging.
This review therefore focuses on SLNB in early breast cancer patients, feasibility of SLNB in patients receiving NAC, novel techniques for SLNB, and ongoing clinical trials about SLNB in breast cancer.
Section snippets
Search strategy and quality assessment of studies
We searched English language literature/abstracts in PubMed and San Antonio Breast Cancer Symposium and ongoing trials in the ClinicalTrials.gov database. The American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines for breast cancer were also referred. The search strategy focused on SLNB in breast cancer. Reference lists of articles were manually searched for relevant articles. The details of search
Clinical trials comparing SLNB and ALND
Since late 20th century, five randomized clinical trials have been performed to evaluate the efficacy and safety of SLNB in early breast cancer patients (Mansel et al., 2006, Krag et al., 2007, Zavagno et al., 2008, Veronesi et al., 2010, Gill, 2009). The primary and secondary outcome measures of those trials mainly focused on arm morbidity and QoL, with the National Surgical Adjuvant Breast and Bowel Project (NSABP) B32 trial (Krag et al., 2007), Milan trial (Veronesi et al., 2010) and Gruppo
Timing of SLNB in patients with clinically negative lymph nodes planned to receive NAC
A number of studies (Kuehn et al., 2013, Hunt et al., 2009, Classe et al., 2009, Agarwal et al., 2016, Kida et al., 2015) have established that the SLN identification rate and FNR are comparable before and after NAC in patients with clinically node-negative disease. The SENTinel NeoAdjuvant (SENTINA) trial analysed 1737 patients in four arms. SLNB was applied for ALN staging before NAC in patients with clinically negative nodes (cN0) (Arm A and arm B). For patients with clinically positive
Indocyaninegreen optical imaging guided SLNB
In the past decade, fluorescent optical intraoperative image-guided SLNB has become more widely used. With this technique, SLNs are identified by fluorescence emitted from dyes that accumulate in the SLNs. This fluorescence can be seen in real-time on a monitor even through the skin, providing a map for SLNs detection. This is an improvement over the blue dye method, which requires the underlying tissue to be exposed and relies more on the surgeons’ experience. For fluorescent optical
Conclusion and future perspective
The concept of surgical management of ALN in patients with breast cancer has converted from a major invasive surgery to minimal invasive and selective surgery. In the past two decades, the application of SLNB in patients with early breast cancer has been well established, and thus the indication of ALND narrowed. In the coming years, research will focus on the omission of axillary surgery in selected patients who have a low priori risk of ALN metastasis. SLNB after NAC achieves comparable SLN
Funding
This work was supported by The Abel Tasman Talent Program (ATTP) of the University of Groningen, Natural Science Foundation Committee (No. 81302331), Major International Collaborative Research Project of NSFC (81320108015), and Guangdong Provincial Key Laboratory on Breast Cancer Diagnosis and Treatment Research.
The study funders did not participate in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to manuscript
Conflicts of interest
The authors have no conflicts of interest to disclose.
Acknowledgements
We would like to thank Dr. Rick G. Pleijhuis for kindly providing us the material for Fig. 1.
References (79)
- et al.
Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review
Lancet Oncol.
(2014) How do the AMAROS trial results change practice?
Lancet Oncol.
(2014)- et al.
Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial
Lancet Oncol.
(2014) - et al.
Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients
Am. J. Surg.
(2016) - et al.
Timing of the sentinel lymph node biopsy in breast cancer patients receiving neoadjuvant therapy − recommendations for clinical guidance
Eur. J. Surg. Oncol.
(2013) - 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) - et al.
Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: S entinel node vs O bservation after axillary U ltraSou ND)
Breast
(2012) - et al.
De-escalation of axillary surgery in early breast cancer
Lancet Oncol.
(2016) - et al.
A prospective feasibility study of sentinel node biopsy by modified Indigocarmine blue dye methods after neoadjuvant chemotherapy for breast cancer
Eur. J. Surg. Oncol.
(2015) - et al.
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.
(2007)
Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial
Lancet Oncol.
Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study
Lancet Oncol.
Partial axillary lymph node dissection inferior to the intercostobrachial nerves complements sentinel node biopsy in patients with clinically node-negative breast cancer
BMC Surg.
Survey of complications of indocyanine green angiography in Japan
Am. J. Ophthalmol.
The use of indocyanine green to detect sentinel nodes in breast cancer: a prospective study
Eur. J. Surg. Oncol.
Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Ann. Oncol.
Assessing the effects of neoadjuvant chemotherapy on lymphatic pathways to sentinel lymph nodes in cases of breast cancer: usefulness of the indocyanine green-fluorescence method
Breast
The diagnostic performance of sentinel lymph node biopsy in pathologically confirmed node positive breast cancer patients after neoadjuvant systemic therapy: a systematic review and meta-analysis
Eur. J. Surg. Oncol.
The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies
Lancet
Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients: identification rate and influence on axillary treatment
Eur. J. Cancer
Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study
Lancet Oncol.
Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study
Lancet Oncol.
A comparative validation of primary surgical versus post-neo-adjuvant chemotherapy sentinel lymph node biopsy for stage III breast cancers
World J. Surg.
Blue dye is sufficient for sentinel lymph node biopsy in breast cancer
Br. J. Surg.
Morbidity results from the NSABP B-32 trial comparing sentinel lymph node dissection versus axillary dissection
J. Surg. Oncol.
Indocyanine green fluorescence for sentinel lymph node detection in early breast cancer
Ann. Surg. Oncol.
Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study
J. Clin. Oncol.
Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial
JAMA
Methods impacting the false negative rate of sentinel lymph node surgery in patients presenting with node positive breast cancer (T0-T4, N1-2) who received neoadjuvant chemotherapy − results from a prospective trial ACOSOG Z1071 (Alliance)
San Antonio Breast Cancer Symposium 2014
Axillary ultrasound after neoadjuvant chemotherapy and its impact on sentinel lymph node surgery: results from the American college of surgeons oncology group Z1071 Trial (Alliance)
J. Clin. Oncol.
Identification and resection of clipped node decreases the false-negative rate of sentinel lymph node surgery in patients presenting with node-positive breast cancer (T0-T4, N1-N2) who receive neoadjuvant chemotherapy: results from ACOSOG Z1071 (Alliance)
Ann. Surg.
Consensus on sentinel node biopsy
Breast J.
Improved axillary evaluation following neoadjuvant therapy for patientswith node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection
J. Clin. Oncol.
Use of indocyanine green for detecting the sentinel lymph node in breast cancer patients: from preclinical evaluation to clinical validation
PLoS One
Intraoperative imaging-guided cancer surgery: from current fluorescence molecular imaging methods to future multi-modality imaging technology
Theranostics
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.
Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): follow-up of a prospective multi-institutional cohort
San Antonio Breast Cancer Symposium 2016
Optical innovations in surgery
Br. J. Surg.
Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer
Cancer
Cited by (62)
Factors Associated With Node-positive Disease in Estrogen Receptor-Positive Breast Cancer Patients
2024, Journal of Surgical ResearchReconsidering the Role of Frozen Section in Sentinel Lymph Node Biopsy for Mastectomy Patients
2024, Journal of Surgical ResearchPatients with initial nodal involvement due to breast cancer who have received neoadjuvant chemotherapy: Combined sentinel node-radioguided surgery of the pathological node
2022, Revista Espanola de Medicina Nuclear e Imagen MolecularThe value of the intraoperative assessment of the SLN via frozen section in the post Z0011 era
2021, Journal of Gynecology Obstetrics and Human ReproductionClinical and Histopathological Features of Breast Cancer in Iraqi Patients between 2018-2021
2024, Iraqi Journal of Science