Review
Meta-analysis of predictive factors for non-sentinel lymph node metastases in breast cancer patients with a positive SLN

https://doi.org/10.1016/j.ejso.2011.01.006Get rights and content

Abstract

Aims

A meta-analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sentinel node is positive.

Methods

A Medline search was conducted that ultimately identified 56 candidate studies. Original data were abstracted from each study and used to calculate odds ratios. The random-effects model was used to combine odds ratios to determine the strength of the associations.

Findings

The 8 individual characteristics found to be significantly associated with the highest likelihood (odds ratio >2) of NSN metastases are SLN metastases >2 mm in size, extracapsular extension in the SLN, >1 positive SLN, ≤1 negative SLN, tumour size >2 cm, ratio of positive sentinel nodes >50% and lymphovascular invasion in the primary tumour. The histological method of detection, which is associated with the size of metastases, had a correspondingly high odds ratio.

Conclusions

We identified 8 factors predictive of NSN metastases that should be recorded and evaluated routinely in SLN databases. These factors should be included in a predictive model that is generally applicable among different populations.

Introduction

Axillary lymph node status remains a powerful prognostic factor in breast cancer. Sentinel lymph node (SLN) biopsy is an accepted alternative to axillary lymph node dissection (ALND). Data from 7 randomized controlled trials have conclusively demonstrated that SLN biopsy is associated with less arm/shoulder morbidity and better quality of life than ALND.1, 2, 3, 4, 5, 6, 7

SLN biopsy allows more accurate staging and identifies patients most likely to benefit from ALND. The high negative predictive value allows ALND and the associated morbidity to be safely avoided in SLN negative patients.8

Due to its prognostic and therapeutic implications (better locoregional disease control) ALND remains the standard of care for SLN positive patients. However, from the literature it is clear that axillary metastases are limited to the sentinel node in about 40–60% of cases.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 These patients are thus undergoing ALND without therapeutic benefit.

Over the past years multiple studies have been conducted to identify clinicopathological variables that are predictive of non-sentinel node (NSN) metastases in an attempt to select those patients who would benefit most from ALND. These studies demonstrated that different pathologic characteristics of the primary tumour and the sentinel node were associated with an increased likelihood of additional positive NSNs. The aim of the present study was to present an overview of the identified predictors of NSN positivity in cases of a positive SLN and to perform a meta-analysis to yield a pooled association.

Section snippets

Medline search

Two different MEDLINE search strategies were conducted to identify relevant articles published up to July 2009:

  • 1. MeSH Database: “Breast Neoplasms” [Majr] AND “Sentinel Lymph Node Biopsy” [Majr] AND “Lymphatic Metastasis” [Majr] AND “Predictive”.

  • 2. Clinical Queries, category ‘clinical prediction guides,’ sensitive search: positive non-sentinel lymph nodes in breast cancer.

Our first search yielded 13 (out of 60) candidate articles, and our second search yielded 45 (out of 180). Articles from the

Candidate studies

Our MEDLINE searches identified 50 candidate studies. After reviewing the references cited in the selected articles we identified a total of 112 studies.

Excluded studies

After careful assessment, 56 studies were excluded (Fig. 1).

Ten studies were excluded because they only validated a nomogram and did not test for predictive factors.42, 43, 44, 45, 46, 47, 48, 49, 50, 51 Two studies were excluded because the full text was not available.52, 53 Seventeen studies only presented predictive factors for positive

Prevalence of NSN metastases

The reported incidence of NSN tumour involvement varies from about 40–60%.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40Small study populations, the size of the tumours investigated and differences in the extent of histological work-up of SLN and NSN partly explain the range in prevalence of NSN involvement.14

However, it is clear that the sentinel lymph node is the only focus of axillary metastases in a significant

Conflict of interest

There were no conflicts of interest for any of the authors.

Acknowledgements

We thank W. Lemmens for performing the data analysis and for designing the figures.

This study was not funded by an outside source.

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