Review
Evolution in sentinel lymph node biopsy in breast cancer

https://doi.org/10.1016/j.critrevonc.2017.09.010Get rights and content

Abstract

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative (cN0) breast cancer patients without neoadjuvant chemotherapy (NAC). The application of SLNB in patients receiving NAC has also been explored. Evidence supports its use after NAC in pretreatment cN0 patients. Nonetheless, its routine use in all the pretreatment node-positive patients who become cN0 after NAC is unjustified due to the unacceptably high false-negative rate, which can be improved in a subset of patients. Axillary surgery omission in selected patients with a low risk of ALN metastasis has gained more and more research interest because the SLNs are tumor-free in more than 70% of all patients. To avoid drawbacks of conventional mapping methods, novel techniques for SLN detection have been developed and shown to be highly accurate in patients with early breast cancer. This article reviews the progress in SLNB in patients with 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.

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