Elsevier

Surgical Oncology

Volume 20, Issue 4, December 2011, Pages e195-e206
Surgical Oncology

Review
Sentinel lymph node micrometastasis in human breast cancer: An update

https://doi.org/10.1016/j.suronc.2011.06.006Get rights and content

Abstract

Introduction

The advent of sentinel lymph node biopsy (SLNB) and advances in histopathological and molecular analysis techniques have been associated with an increase in micrometastasis (MM) detection rate. However, the clinical significance of sentinel lymph node micrometastasis (SLN MM) continues to be a subject of much debate. In this article we review the literature concerning SLN MM, with particular emphasis on the prognostic significance of SLN MM. The controversies regarding histopathological assessment, clinical relevance and management implications are also discussed.

Methods

Literature review facilitated by Medline and PubMed databases. Cross referencing of the obtained articles was used to identify other relevant studies.

Results

Published studies have reported divergent and rather conflicting results regarding the clinical significance and implications of axillary lymph node (ALN) MM in general and SLN MM in particular. Some earlier studies demonstrated no associations, however most recent studies have found SLN MM to be an indicator of poorer prognosis and to be associated with non-SLN involvement.

The use of adjuvant chemotherapy and/or hormonal manipulation therapy is associated with an improved survival in patients with SLN MM. Complete ALND may be safely omitted provided that adjuvant systemic therapy recommendations are equal to patients with node-positive disease. However, optimal management of SLN MM is yet to conclude.

Furthermore, the identification of MM remains largely dependant on the analytical technique employed and the use of immunohistochemistry (IHC) increases the detection rate of SLN MM. Discrepancies in the histopathological interpretation of TNM classification of SLN tumour burden do exist. Published studies were non-randomized and have significant limitations including a small sample size, limited follow-up period, and lack of standardization and reproducibility of pathological examination of the SLN.

Conclusion

Patients with SLN MM have a poorer prognosis than those who are SLN negative. Therapeutic recommendations regarding patients with SLN MM should be taken in the context of multidisciplinary team setting and in selected cases of SLN MM, complete ALND may be safely omitted. A better reproducibility of pathological interpretation of the TNM classification is required so that future therapeutic guidelines can be applied without confusion.

Highlights

► The presence of SLN MM is an indicator of poorer prognosis in breast cancer. ► Use of adjuvant therapy in SLN MM patients is associated with improved survival. ► Complete axillary dissection may be safely omitted in patients with SLN MM. ► The optimal management of SLN MM is yet to conclude.

Section snippets

Introduction & background

The axillary lymph node (ALN) status at the time of diagnosis is the most powerful predictor of survival in breast cancer (BC) patients [1], [2]. In addition, decisions regarding adjuvant therapies are largely influenced by lymph node status. Axillary lymph node dissection (ALND) remains the gold standard, it provides accurate staging information and local control of the disease; however, the morbidity of this procedure can be high. The sentinel lymph node biopsy (SLNB) has now been confirmed

Search methodology

MEDLINE and PubMed were used to search for relevant articles. Articles identified using the key words “breast cancer” or “sentinel lymph node” or “axillary lymph node” or “lymph node” and “micrometastasis” or “micrometastasis” or “micro metastasis” or “micro metastases” or “micro-metastasis” or “micro-metastases" and “adjuvant therapy” and “evidence” or “prognosis” or “morbidity” or “mortality” or “recurrence” or “ failure” or “survival”. Studies identified were screened for those that focused

The clinical significance of axillary micrometastasis

Published studies have reported divergent and conflicting results regarding the significance and implications of ALN MM in general and SLN MM in particular [14]. Clinical outcome such as overall survival, disease-free survival, loco-regional recurrence and distant metastasis have been evaluated. Furthermore, in patients with SLN MM studies examined the incidence of non-SLN involvement. In the following, we evaluate the incidence of non-SLN metastatic involvement in patients with SLN MM and its

Discussion

The management of breast cancer patients has witnessed dramatic changes in the last two decades. Early diagnosis, breast conserving surgery, the advent of SLNB and advances in adjuvant therapies have replaced old practices. One of the key drivers of this change has been an improved understanding of the natural history and tumour biology of BC. Now, the biological model that considers BC as a systemic disease with disseminated MM at the time of diagnosis [87] is considered an acceptable way of

Conclusion

The latest published evidence suggests that the SLN MM is likely to have significant prognostic implications in early-stage BC. There is a growing body of evidence that patients with SLN MM have a poorer prognosis than those who are SLN negative. SLN MM is likely to be associated with non-SLN involvement some of which are macro-metastatic foci. In the absence of level 1 evidence, decisions about the management options of patients with SLN MM should be taken in the context of risk estimate

Conflict of interest statement

The authors declare that they have no competing interests.

References (134)

  • L. Fortunato et al.

    Sentinel lymph node biopsy in women with pT1a or “microinvasive” breast cancer

    Breast

    (2008)
  • S. Giard et al.

    Surgical implications of sentinel node with micrometastatic disease in invasive breast cancer

    Eur J Surg Oncol

    (2004)
  • M. Gipponi et al.

    The role of axillary lymph node dissection in breast cancer patients with sentinel lymph node micrometastases

    Eur J Surg Oncol

    (2006)
  • M.H. Leidenius et al.

    The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases

    Eur J Surg Oncol

    (2005)
  • C.E. Cox et al.

    Significance of sentinel lymph node micrometastases in human breast cancer

    J Am Coll Surg

    (2008)
  • J. Reed et al.

    Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective East Carolina University/Anne Arundel Medical Center Sentinel Node Multicenter Study

    J Am Coll Surg

    (2009)
  • A.S. Gur et al.

    Predictive probability of four different breast cancer nomograms for nonsentinel axillary lymph node metastasis in positive sentinel node biopsy

    J Am Coll Surg

    (2009)
  • G. D’Eredita et al.

    Sentinel lymph node micrometastasis and risk of non-sentinel lymph node metastasis: validation of two breast cancer nomograms

    Clin Breast Cancer

    (2010)
  • L.N. Broekhuizen et al.

    The incidence and significance of micrometastases in lymph nodes of patients with ductal carcinoma in situ and T1a carcinoma of the breast

    Eur J Surg Oncol

    (2006)
  • A.M. Neville et al.

    Occult axillary lymph-node micrometastases in breast cancer

    Lancet

    (1990)
  • G.P. Kuijt et al.

    The prognostic significance of axillary lymph-node micrometastases in breast cancer patients

    Eur J Surg Oncol

    (2005)
  • G.H. Sakorafas et al.

    The clinical significance of axillary lymph node micrometastases in breast cancer

    Eur J Surg Oncol

    (2004)
  • C.L. Carter et al.

    Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

    Cancer

    (1989)
  • H.A. Hatoum et al.

    Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer

    Ann Surg Oncol

    (2009)
  • G. Gill

    Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC): a randomized controlled surgical trial

    Ann Surg Oncol

    (2009)
  • A. Goyal et al.

    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)
  • N. Patani et al.

    Current management of DCIS: a review

    Breast Cancer Res Treat

    (2008)
  • A.J. Maaskant et al.

    Stage migration due to introduction of the sentinel node procedure: a population-based study

    Breast Cancer Res Treat

    (2009)
  • C.H. van Deurzen et al.

    Predictive value of tumor load in breast cancer sentinel lymph nodes for second echelon lymph node metastases

    Cell Oncol

    (2007)
  • N. Patani et al.

    The clinical significance of sentinel lymph node micrometastasis in breast cancer

    Breast Cancer Res Treat

    (2009)
  • K. Khalifa et al.

    The accuracy of intraoperative frozen section analysis of the sentinel lymph nodes during breast cancer surgery

    Int J Fertil Womens Med

    (2004)
  • K. Tew et al.

    Meta-analysis of sentinel node imprint cytology in breast cancer

    Br J Surg

    (2005)
  • Schwartz GF, Giuliano AE, Veronesi U. Proceedings of the consensus conference on the role of sentinel lymph node biopsy...
  • G.H. Lyman et al.

    American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer

    J Clin Oncol

    (2005)
  • M. Rivera et al.

    Controversies in surgical pathology: minimal involvement of sentinel lymph node in breast carcinoma: prevailing concepts and challenging problems

    Int J Surg Pathol

    (2004)
  • R.R. Turner et al.

    Pathologic features associated with nonsentinel lymph node metastases in patients with metastatic breast carcinoma in a sentinel lymph node

    Cancer

    (2000)
  • D.L. Weaver et al.

    Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma: a multicenter study

    Cancer

    (2000)
  • G. Cserni

    A model for determining the optimum histology of sentinel lymph nodes in breast cancer

    J Clin Pathol

    (2004)
  • K. Dowlatshahi et al.

    Occult metastases in sentinel nodes of 200 patients with operable breast cancer

    Ann Surg Oncol

    (2001)
  • Y. Tamaki et al.

    Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay

    Clin Cancer Res

    (2009)
  • M. Martin et al.

    Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes

    Eur J Surg Oncol

    (2009)
  • T.B. Julian et al.

    Novel intraoperative molecular test for sentinel lymph node metastases in patients with early-stage breast cancer

    J Clin Oncol

    (2008)
  • M. Visser et al.

    Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer

    Int J Cancer

    (2008)
  • G. Viale et al.

    Comparative evaluation of an extensive histopathologic examination and a real-time reverse-transcription-polymerase chain reaction assay for mammaglobin and cytokeratin 19 on axillary sentinel lymph nodes of breast carcinoma patients

    Ann Surg

    (2008)
  • R.E. Mansel et al.

    Detection of breast cancer metastasis in sentinel lymph nodes using intra-operative real time GeneSearch BLN Assay in the operating room: results of the Cardiff study

    Breast Cancer Res Treat

    (2009)
  • M. Kurosumi et al.

    Significance and problems of histopathological examination and utility of real-time reverse transcriptase-polymerase chain reaction method for the detection of sentinel lymph node metastasis in breast cancer

    Breast Cancer

    (2007)
  • M. Tsujimoto et al.

    One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients

    Clin Cancer Res

    (2007)
  • B.A. Carter et al.

    Benign transport of breast epithelium into axillary lymph nodes after biopsy

    Am J Clin Pathol

    (2000)
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