A prospective study of the value of axillary node sampling in addition to sentinel lymph node biopsy in patients with breast cancer

doi:10.1016/S0748-7983(03)00076-3

European Journal of Surgical Oncology

Volume 29, Issue 6, August 2003, Pages 526-531

https://doi.org/10.1016/S0748-7983(03)00076-3 Get rights and content

Abstract

Aims: Limitations of sentinel lymph node biopsy (SLNB) include the occurrence of false negative (FN) results and the need to further treat SLNB positive axillae. The aims of this study were to:

(1) compare the accuracy of SLNB alone to a combined SLNB and axillary sampling procedure (SLNB+AS).

(2) evaluate if the additional AS could identify those SLNB positive cases with no further disease in the axilla.

Methods: Sixty-seven combined SLNB+AS procedures were performed prospectively in 66 patients, followed by Level II axillary dissection. Additionally sampled nodes were recorded if they were clinically suspicious or not at intra-operative palpation.

Results: The FN rate for SLNB alone was 14.3%, whilst that for SLNB+AS was reduced to 3.6%. However, the benefit of additional sampling was only seen in those cases with tumours ≥3 cm and clinically suspicious nodes (n=12). Of 12 cases with a positive SLN but negative AS, 4 (30%) were found to have disease elsewhere in the axilla.

Conclusion: SLNB is inaccurate in the presence of suspicious nodes found at operation and careful palpation and sampling of these nodes is recommended, especially with larger tumours. In SLNB positive patients, AS is unreliable in predicting those patients with no further disease in the axilla.

Introduction

Currently there is considerable interest in sentinel lymph node biopsy (SLNB) as an alternative staging technique to conventional axillary surgery in women with primary breast cancer. Sentinel node biopsy has been reported as a minimally invasive, accurate means of staging the axilla, allowing selective axillary dissection only in those patients with axillary nodal disease.1., 2. Women with a tumour free sentinel node (SLN) are highly unlikely to have metastases in the remainder of the axilla³ and can therefore be spared the potential morbidity of a full axillary dissection. Furthermore, since fewer nodes are excised, a more detailed histological examination is feasible thus improving staging accuracy.

The two main parameters for assessing the success of a SLNB practice are the identification rate and the false negative (FN) rate. A completion axillary lymph node dissection (cALND) should be carried out until an acceptable level of accuracy has been demonstrated. An identification rate of >90% and a FN rate of ≤5% have been suggested as acceptable.⁴ A number of studies from experienced centres have reported excellent results with FN results below 5%.1., 2., 5., 6., 7. However, many more studies have shown FN rates higher than the 5% guidelines, even as high as 29%.8., 9., 10., 11.

A number of factors are thought to contribute to FN results. One important factor is a heavy tumour load in the true SLN which is thought to result in the diversion of the blue dye or isotope to a tumour free ‘neo-sentinel node’.¹² Several reports in the literature have highlighted the importance of palpating the axilla for clinically suspicious non-SLNs and have advocated biopsy of such nodes to minimise FN results.11., 13., 14., 15., 16. These reports suggest palpation for clinically involved nodes may reduce but not entirely eliminate all FN cases.

Axillary sampling is frequently used in the UK as a means of staging the axilla, either routinely for all patients or selectively in those patients thought to be at low risk of axillary disease. This method involves palpating the lower axilla and excising a minimum of four lymph nodes thought most likely to contain metastases. Several studies have shown AS techniques to be as accurate as ALND with no difference in axillary recurrence rates between women staged by the two methods.17., 18., 19. Other studies, however, have concluded that AS is not as accurate as ALND and metastases may be missed if less than 10 nodes are examined.20., 21.

The first aim of our study was to compare the accuracy of a ‘combined sentinel node+sampling procedure’ (SLNB+AS) to SLNB alone. We have further evaluated whether additional AS is useful only in those patients with clinically suspicious nodes or if routine additional sampling in all cases further improves accuracy.

The second aim of the study was to evaluate if in the presence of a tumour positive SLN, a tumour free AS predicts those patients with no further disease in the axilla. A number of studies have shown that in 38–66% of cases with metastasis in the SLN, no further disease is found when cALND is undertaken.1., 2. We investigated whether women with a positive SLN but no further disease in the axilla could be identified by additional AS and therefore spared a cALND.

Section snippets

Patients and methods

As part of an on-going study of sentinel node biopsy in women with primary invasive breast cancer, 67 combined sentinel node+sampling procedures were performed in 66 consecutive women (1 patient with bilateral breast cancer). All patients were operated on by the same surgeon (PSS) between February 2000 and July 2001. Local Ethical Committee approval was given for the study and written informed consent was obtained from all participants.

The study group consisted of both screen detected and

Results

The median age of the patients was 55 yr (range 27–86 yr). Lymphoscintigraphy identified sentinel nodes in 49/66 cases (74.2%). Intra-operatively sentinel nodes were identified in 65/67 cases (identification rate 97.0%). The median number of sentinel nodes excised per case was 2 (range 1–8) and the median number of nodes excised for the combined SLNB+AS was 5 (range 2–14). The median total number of nodes harvested (SLNB+AS+cALND) was 16 (range 7–35).

In 83% cases the sentinel node(s) were

Discussion

The major limitation of the technique of sentinel node biopsy is the FN rate and several explanations have been suggested as to why this may occur. Firstly, tumour cells may occasionally pass through to second tier nodes whilst tracers used to identify the SLN remain in the first echelon nodes. The second suggestion is that lymphatic flow from a particular area may differ at times resulting in tumour cells and tracers migrating to different nodes.²² These two problems may be difficult to avoid.

Acknowledgements

Dr S.-Y. Chan and Dr J. Gearty, Consultant Pathologists, City Hospital. Dr A. Notghi, Consultant in Nuclear Medicine, City Hospital. Mr I. Donovan, Consultant Surgeon, City Hospital.

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Cited by (20)

Sentinel node biopsy versus low axillary sampling in women with clinically node negative operable breast cancer
2013, Breast
Citation Excerpt :
Some centers in the UK have adopted a 4-node axillary sampling (4NAS) [12,13] to predict axillary nodal status. A modification of 4NAS is the concurrent use of blue dye to improve identification of lymph nodes [14–17]. We reasoned that predicting axillary lymph node status would be more easily achieved by excising fatty tissue in an anatomically defined area in the lower axilla or low axillary sampling (LAS).
Sentinel node biopsy (SNB) was initially conceived as excision of the first station axillary lymph node(s) (LN) identified by radioactive and/or blue dye uptake. The definition was subsequently enlarged to also include palpable lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the excision of this combination of nodes might be best achieved by sampling the lower axilla.
Each patient underwent low axillary sampling (LAS) and identification of SN in the excised specimen followed by complete axillary lymph node dissection (ALND). LAS was defined as excision of all fibrofatty tissue overlying the second digitation of serratus anterior below the intercostobrachial nerve and was carried out following a pre-operative injection of radioactive colloid and an intra-operative injection of blue dye. Blue and/or hot nodes (B&/HN) in the dissected tissue and remaining axilla, along with any palpable nodes within the sampled tissue, were defined as SN. The primary endpoint of the study was to compare false negative rates (FNR) of SN with that of LAS in predicting axillary LN status (NCT00128362).
The study was performed between March 2004 and December 2011 in 478 women with clinically node negative axilla. On histopathological evaluation the median tumor size was 2.5 cm and axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%, 95% CI 8.1–19.4) and LAS (10.5%, 95% CI 6.6–16.2) were not significantly different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95% CI 22.5–36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p = 0.0003).
LAS is as accurate as SNB in predicting axillary LN status in women with clinically node negative operable breast cancer. Confining SNB procedure to excision of B&/HN, significantly increases the risk of leaving behind metastatic lymph nodes in the axilla. LAS is an effective and low cost procedure that minimizes axillary surgery and can be implemented widely.
Registry Name: Clinicaltrials.gov.
Registration Number: NCT00128362.
Axillary Dissection
2012, Current Problems in Cancer
Use of Reoperative Sentinel Lymph Node Biopsy in Breast Cancer Patients
2008, Journal of the American College of Surgeons
Citation Excerpt :
The ability of reoperative SLNB to predict the presence or absence of axillary nodes positive for metastasis has proved to be reliable. Positive SLNs were found in 9 of 45 (20%) successful reoperative procedures and are within the range of published values for patients undergoing SLNB for the first time.7,13,16-18 There have been no local, axillary recurrences in any patients after a mean of 26 months followup.
Ipsilateral breast recurrence or second primary breast cancer can develop in patients who have undergone breast conservation and sentinel lymph node biopsy (SLNB). This brings into question the necessity of complete axillary lymph node dissection (CALND) versus a second SLNB (remapping). Our objective is to determine the feasibility of a reoperative SLNB.
A review of patients receiving a reoperative SLNB between April 1994 and December 2006 was conducted with IRB approval. Fifty-six patients underwent a second SLNB on the ipsilateral side an average of 42.5 months after their first SLNB.
Sentinel lymph nodes were successfully remapped in 45 of 56 (80.4%) patients. Of 45 patients successfully remapped, 36 (80%) were node negative and were spared CALND. There was only 1 patient (2.2%) in whom a sentinel lymph node was identified outside of the ipsilateral axilla. At 26 months mean followup for the second SLNB, there have been no axillary recurrences and 1 death.
Our findings demonstrate that remapping sentinel nodes in patients with ipsilateral recurrence or new primary breast cancer after SLNB achieved success in 80.4% of patients. Overall, 80.0% (36 of 45) of the successfully remapped patients were spared a CALND.
Management of the axilla in women with breast cancer
2007, Breast
Citation Excerpt :
This did not include those who purported to practice sentinel node biopsy and did not distinguish between blind and dye-assisted sampling. In a prospective comparison study involving 200 patients, Macmillan concluded that sentinel node biopsy may have little to offer four node samplers.14,15 The sentinel node was present in the four node sample in 77% of the cases, whilst no sentinel node was found in 4% of the cases.
There remain several outstanding questions relating to management of the axilla in women with early stage breast cancer. This paper summarises the outcome of a national debate aimed at discussing certain key issues including a) whether axillary dissection has any survival advantage b) is an axillary staging procedure always necessary c) what is the optimum method of staging the axilla and d) whether an axillary dissection is always necessary in cases of a positive sentinel node. Electronic voting was undertaken at the beginning and end of the debate and results are compared and presented herein.
A clinicopathological scoring system to select breast cancer patients for sentinel node biopsy
2006, European Journal of Surgical Oncology
Citation Excerpt :
It is postulated that involved lymph nodes associated with large tumours may have blocked afferent pathway to the lymph node giving rise to false-negative rate. In some studies, preoperative chemotherapy and large tumour size have been shown to be associated with an unacceptably high false-negative rate for sentinel node biopsy.27,28 Having fewer numbers of node to stage axilla leads to loss of prognostic information such as final number of involved nodes and extra-nodal spread.29
Selecting patients for sentinel node biopsy, based on grade and size of the primary tumour, often results in the need for a second operation of axillary clearance since intra-operative pathological assessment of sentinel node is in its evolution at present. It may be possible to refine the clinical criteria to select patients for the type of axillary surgery.
By using a score based on clinicopathological predictors of axillary lymph node involvement, we hypothesise that it may be possible to identify patients at high or low risk of nodal involvement. This information can be used to assist patients to make informed decision regarding risks and benefits of sentinel node biopsy or axillary clearance.
A score was devised based on the clinicopathological variables of 113 patients to assess the likelihood of lymph node positivity. This score was validated on an independent data set of 89 patients who underwent sentinel node biopsy and axillary surgery. Based on the score, patients were divided into two groups, high score and low score groups. For the low score group, lymph node positivity was 18% for the original score and 24% for the validation score. Lymph node positivity rate was 67% for the high score group for the original series and 65% for the validation series of patients.
A clinicopathological scoring system can assist in selecting patients with breast cancer for sentinel node biopsy.
Continued axillary sampling is unnecessary and provides no further information to sentinel node biopsy in staging breast cancer
2005, European Journal of Surgical Oncology
Citation Excerpt :
Nodes that are felt to be suspicious at the time of the mapping procedure irrespective of radio-isotope or dye uptake should also be biopsied as sentinel nodes.9,19,25,26 Several studies have evaluated the role of axillary sampling either to validate the technique, to stage the axilla or as an adjunct to predicting the status of the residual axilla following a positive SLNB.24,27–29 Hoar and Stonelake have shown that by performing an axillary sampling procedure in addition to a SLNB lowered the false negative rate from 14.3 to 3.6% and increased the overall accuracy and sensitivity.28
Sentinel lymph node biopsy (SLNB) has become increasingly accepted as a diagnostic method to stage the axilla in breast cancer, selecting women with a positive sentinel node for completion axillary clearance. As SLNB became established, many surgeons supplemented SLNB to sample a minimum of four lymph nodes, on the assumption that the four-node technique is supported by randomised trial data. We hypothesised that the practice of undirected sampling to supplement SLNB adds little information to the status of the residual axilla.
One hundred and sixty-five patients with early breast cancer were studied. Following successful identification of the sentinel node, 84 women had completion axillary dissection and 81 women had an axillary sample with at least four nodes available for pathological assessment.
Following successful identification of the sentinel node in 165 patients, the false negative rate (FNR) was 2/44=4.5% (95% CI 0.6–15.5), sensitivity 42/44=95.5% (84.5–99.4) and negative predictive value (NPV) 121/123=98.4% (94.2–99.8). In the axillary dissection cohort, the FNR was 2/26=7.7% (0.9–25.1), sensitivity 24/26=92.3% (74.9–99.1) and NPV 58/60=96.7% (88.5–100). In the axillary sample group, the FNR was 0/18=0% (0–18.5), sensitivity 18/18=100% (81.5–100) and NPV 63/63=100% (94.3–100). The SLNB was the only positive node in 12/26 (46.2%) in the axillary dissection group and 10/18 (55.6%) in the axillary sampling group. There was no patient in the axillary sampling group where the sample node was positive and the sentinel node negative.
Once SLNB is validated within the multidisciplinary unit, undirected sampling of the axilla following identification of the sentinel node(s) is unnecessary. The additional sampling of non-sentinel nodes has no role to play either in the assessment of a potential false negative SLNB nor as predictive information on the status of the residual axillary nodes.

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^☆: Work presented to the Nottingham International Breast Cancer Meeting, September 2001.

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A prospective study of the value of axillary node sampling in addition to sentinel lymph node biopsy in patients with breast cancer☆

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Acknowledgements

Lancet

J Am Coll Surg

Eur J Surg Oncol

Eur J Surg Oncol

Surgery

Eur J Surg Oncol

Eur J Surg Oncol

Lancet

Sentinel lymphadenectomy in breast cancer

J Clin Oncol

Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma

Ann Surg

Proceedings of the Consensus Conference on the Role of Sentinel Lymph Node Biopsy in Carcinoma of the Breast 2001

Hum Pathol

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer

JAMA

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer

Ann Surg