Elsevier

The Breast

Volume 13, Issue 6, December 2004, Pages 494-501
The Breast

ORIGINAL ARTICLE
A decision aid for predicting non-sentinel node involvement in women with breast cancer and at least one positive sentinel node

https://doi.org/10.1016/j.breast.2004.08.005Get rights and content

Summary

Background: Several clinical trials are re-evaluating the management of the axilla after sentinel node (SN) biopsy. Approximately 50–70% of patients with positive SN have no further nodal involvement. Estimates of the risk of non-sentinel node (NSN) involvement would aid decisions regarding further axillary surgery.

Methods: Clinical and pathological variables for 82 breast cancer patients with metastasis to at least one SN, were used to find independent predictors of the status of NSNs.

Results: NSN metastases were found in 46.3% of patients. In a regression model patient age, proportion of SN replaced by metastasis and number of SNs were independent predictors of NSN status.

Conclusion: Data available after SN biopsy allow estimation of the risk of NSN metastases among patients with positive SNs. Individualised estimates of the risk of NSN involvement may facilitate discussions regarding the trade off between the likely benefits of further axillary surgery and the morbidity of this procedure.

Introduction

Several large validation studies have confirmed that breast cancer patients whose sentinel nodes (SN) are free of metastases have low rates of non-sentinel node (NSN) involvement of 5–10% in experienced hands. The high predictive value of a histologically negative SN has led some groups to abandon routine axillary clearance (AC) for this subset of patients.1, 2 By contrast, when the SN is involved by metastasis, only 30–50% of patients have further metastases to NSNs.3, 4, 5 This observation has prompted the question as to whether there are subsets among SN positive breast cancer patients with low risks of NSN involvement so that AC and its associated morbidity may be avoided.

A small number of studies have attempted to predict the status of the remaining axillary nodes, mostly by univariate analysis. The size of the metastasis in the SN, using the arbitrary figure of 2 mm, by convention defining nodal micrometastases, has received most attention.3, 4, 6 Some groups have suggested that patients with micrometastases may avoid AC, but since approximately 25% of patients with SN metastases ⩽2 mm5, 6 and 15.6% of those with ⩽1 mm SN metastases6 have involved NSNs, this simple heuristic alone is an unsatisfactory basis for avoidance of AC.

By analysis of clinical and pathological characteristics of a series of breast cancers with metastatic involvement to at least one SN, the purpose of this study is to identify independent predictors of the status of the remaining axillary nodes.

Section snippets

Materials and methods

All patients with primary breast cancer treated by SN biopsy and AC at the Royal Adelaide Hospital Breast Unit between June 1995 and September 2000 who had at least one positive SN were included in this study. The SNs were mapped by a combination of blue dye and lymphocintigraphy after peritumoural injection of technetium TC99 and blue dye. The details of the clinical and pathologic features of a subset of these tumours are reported elsewhere.7

The primary tumours were processed routinely. The

Statistical methods

Statistical analysis was done using the S-plus statistical software package.11 Univariate analysis assessed clinical and pathological variables for their association with the presence of any NSN metastases. The χ2 test was used for categorical variables. The Wilcoxon rank sum test was used for continuous variables.

For multivariate analysis a logistic regression was used. Using step-wise search procedures, a variety of models were tested for their ability to predict the likelihood of NSN

Results

Eighty-two patients with breast cancer metastatic to at least one SN were included in the study. The patients’ mean age was 54.9 years (S.D. 11.7 years). The mean tumour diameter was 25.6 mm (S.D. 13.8 mm). The mean number of SNs removed was 2.2 nodes (S.D. 1.3). The mean number of NSNs removed was 11.8 nodes (S.D. 5.2). NSN metastases were found in 38 cases (46.3%).

Significant patient and tumour characteristics

The results of univariate analyses for the parameters assessed are demonstrated in Table 1. A strong trend was found in younger women being more likely to have positive NSNs (P=0.055). The effect of age was gradual without a threshold age associated with a dramatic change in risk (Table 2).

Screen-detected tumours with positive SN were less likely to have NSN metastases. While 23.53% of tumours detected by screening mammography had NSN metastases, 51.61% of patients with symptomatic tumours had

Multivariate analysis

Among all of the features assessed, the logistic regression model that predicted the status of the NSNs most successfully in this study selected patient age, proportion of SN replaced by metastasis and the total number of SNs submitted. Other variables did not improve the fit of the final model significantly and were not retained by the model.

Discussion

In experienced hands SNs can be identified in over 90% of breast cancer patients and histological examination of these nodes provides accurate staging information, particularly when the SNs are negative.13 International studies comparing SN biopsy to AC in women with early breast cancer are nearing completion. These include the NSABP32 trial in North America, the ALMANAC trial in the United Kingdom and the SNAC in Australia and New Zealand. It is likely that the results of these studies will

Conclusions

The international trials evaluating SN biopsy in breast cancer are nearing completion. They are expected to demonstrate that the majority of breast cancer patients may be staged effectively by SN biopsy. Since 50–70% of women with involved SNs do not have further axillary disease, the management of the axilla after SN biopsy in such women will then have to be assessed for each patient. Patients’ preferences are an important consideration in this discussion. Given the morbidity associated with

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