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Breast cancer is one of the most-researched areas of medicine, and
best practice has evolved from well conceived and conducted
randomised trials. For instance, we know that outcomes after
breast-conserving surgery and mastectomy are equivalent, that
adjuvant therapies improve survival, and that breast screening
reduces mortality. Yet, many questions remain unanswered.
In breast cancer, the status of the axillary nodes is one of the
strongest prognostic indicators, and a major factor in determining
adjuvant systemic therapy. Although the landmark National Surgical
Adjuvant Breast Project (NSABP 04) study concluded that treatment of
the axilla per se did not affect long-term
survival,1 the issue of whether or not
good local control (ie, radiotherapy or axillary clearance) affects
survival is still debated,2,3 and the evidence to date
suggests that at least Level 2 dissection -- 10 or more nodes -- is
required for reliable assessment of axillary
involvement.4
A proportion of women will experience complications after axillary
dissection, including shoulder dysfunction, paraesthesiae and
chronic lymphoedema.5 The question then arises:
can we avoid axillary clearance in selected patients -- for example,
by the technique of axillary node biopsy? This technique is based on
the assumption that the status of the first node in the draining basin
of the primary tumour is an accurate indicator of the overall status of
that field of drainage; with a tumour-free sentinel node, axillary
dissection may be unnecessary.
Now that screening and evidence-based improvements to treatment are
starting to have an impact on survival, we need to be wary of replacing
well established methods with new techniques that have not been
rigorously evaluated. Can sentinel node biopsy be implemented
safely, with real long term benefits for our patients?
In this issue of the Journal , Kollias and
colleagues report their results with the sentinel node biopsy
technique,6 which compare favourably
with other international series. Sentinel nodes were identified
successfully in 95 of the 117 women by a combination of three
techniques -- lymphoscintigraphy, blue dye and a hand-held gamma
probe (the latter two for intraoperative identification).
Lymphoscintigraphy is an important prelude to sentinel node biopsy,
but in the series of Kollias et al it successfully mapped the sentinel
node in only 63.2% of cases. However, the authors point out that they
were able to improve the accuracy by increasing the injection volume.
The skill and persistence of the nuclear physician are key factors in
obtaining optimal lymphoscintigraphy. In Australia, we are
fortunate to have a radiopharmaceutical (99mTc-labelled antimony
sulfide colloid) that is superior to those available in other
countries. This means that we may produce more accurate maps of
lymphatic drainage, and thereby identify sentinel nodes more often.
Research reported from the Royal Prince Alfred Hospital in Sydney has
shown that drainage patterns from individual tumours can be quite
unexpected.7 This new area of study means
that we will have to re-evaluate the whole notion that "skip
metastases" occur, and their significance in determining overall
prognosis.8
If a decision on whether to dissect the axilla had been based on a
confirmed tumour-negative sentinel node, then 66 of the 117 women in
the study of Kollias and colleagues would have been spared axillary
dissection, although in two women this would have been a false
negative diagnosis (two of the 31 women with nodal involvement had
sentinel nodes negative for tumour). This rate (6.5%) is comparable
with those in other series.9,10 Although we should be
concerned about the false negative rate of sentinel node biopsy, we
should also recognise that some occult metastases are not detected in
standard haematoxylin-eosin histopathological sections. With
standard staining methods, the false negative rate in a series of
patients reported from St Vincent's Hospital in Melbourne was 12%; in
that series, antimucin monoclonal antibodies showed
micrometastatic deposits in 41 of 343 patients previously
classified as having node-negative breast cancer by
haematoxylin-eosin staining.11
False negative assessments are inevitable when lymph nodes are
sampled, but the more detailed examination of one or two "sentinel"
nodes may prove more beneficial than the standard examination of many
nodes. The detection of micrometastatic deposits introduces a new
area of uncertainty requiring further study -- we have yet to
determine their significance. How do they affect prognosis and how
should we treat them? Ongoing evaluation of locoregional recurrence
and distant disease is essential.
At first glance, sentinel node biopsy appears invitingly easy, but
success in completing the sometimes technically difficult
procedures involved will define the oncological relevance of the
technique. Simply removing a "hot" or "blue" node is not enough -- we
have to reappraise our indications for treating the internal mammary
nodes and the supraclavicular nodes, as well as those in the axilla, as
nodes from more than one site may be involved. It is equally important
that women with breast cancer be managed in consultation with
oncologists: women treated in a multidisciplinary setting tend to
have better outcomes.12
While Kollias et al conclude that sentinel node biopsy is an accurate
method of assessing axillary lymph node status, the accuracy has
varied in other series. Reported detection rates range from 66% to
100% and false negative rates from zero to 17%.13 Why is there such a
discrepancy? A possible explanation is the different techniques
used in individual series. Some surgeons used only one method of
localisation; others used different combinations of the three
techniques -- different dyes, different radiopharmaceuticals,
different times between injection and surgery, different methods of
injection, and even different criteria by which sentinel nodes are
searched for and removed.
In Australia, we have a window of opportunity to work towards a
standardised approach to sentinel node biopsy, using agreed
protocols and prospective and uniform data collection. Kollias and
colleagues, and other representatives from the major breast units
and the Section of Breast Surgery of the Royal Australasian College of
Surgeons, are working together and have proposed an Australasian
prospective randomised trial with the capacity to involve all
surgeons who are interested in breast cancer management.
New techniques require proper evaluation. As a group, surgeons have
been quick to adopt new procedures before scientific
validation.14 In addition, consumer
pressures, and sometimes market pressures, are at work. For
comparison, consider laparoscopic cholecystectomy, which has now
gained widespread approval. The learning curve was steep -- the early
reports of this technique were full of enthusiasm and the procedure
was adopted rapidly. There is no doubt that, in those early days,
considerable morbidity for many patients could have been avoided
with more caution and less haste.15 The technical aspects of
these two quite different operations are not comparable; the
parallel to be drawn relates to the way new procedures may be
incorporated into, and perhaps finally adopted as, standard
procedures. It therefore behoves us to ensure that, with any new
procedure, consumers are not placed at increased risk, particularly
if it is performed with limited expertise.
Owen A Ung
Clinical Services Director
New South Wales Breast Cancer
Institute, and Breast and Endocrine Surgeon
Westmead Hospital,
Sydney, NSW
owenuATbci.org.au
Neil R Wetzig
Chairman, Section of Breast Surgery
Royal Australasian College of
Surgeons and Senior Surgeon
Princess Alexandra Hospital,
Brisbane, QLD
- Fisher B, Redmond C, Fisher ER, et al. Ten-year results of a
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Harris JR, Osteen RT. Patients with early breast cancer benefit
from effective axillary treatment. Breast Cancer Res Treat
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Overgaard M, Hansen PS, Overgaard J, et al. Postoperative
radiotherapy in high-risk premenopausal women with breast cancer
who receive adjuvant chemotherapy. Danish Breast Cancer
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Axelsson CK, Mouridsen HT, Zedeler K, on behalf of The Danish Breast
Cancer Cooperative Group (DBCG). Axillary dissection of level I and
II lymph nodes is important in breast cancer classification. Eur J
Cancer 1992; 28A: 1415-1418.
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NHMRC National Breast Cancer Centre. Lymphoedema: prevalence,
risk factors and management: a review of research. Sydney: NBCC,
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Kollias J, Gill PG, Chatterton BE, et al. Reliability of sentinel
node status in predicting axillary lymph node involvement in breast
cancer. Med J Aust 1999; 171: 461-465.
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Uren RF, Howman-Giles RB, Thompson JF, et al. Mammary
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Danforth DN, Findlay PA, McDonald HD, et al. Complete axillary
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Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping
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Krag DN, Ashikaga T, Harlow SH, Weaver DL. Development of sentinal
node targeting technique in breast cancer patients. Breast J
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Hainsworth PJ, Tjandra JJ, Stillwell RG, et al. Detection and
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Br J Surg 1993; 80: 459-463.
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Sainsbury R, Haward B, Rider L, et al. Influence of clinical
workload and patterns of treatment on survival from breast cancer.
Lancet 1995; 345: 1265-1270.
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McIntosh SA, Purushotham AD. Lymphatic mapping and sentinel node
biopsy in breast cancer. Br J Surg 1998; 85: 1347-1356.
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Solomon MJ, McLeod RS. Surgery and the randomised controlled
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The Southern Surgeons Club. A prospective analysis of 1518
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©MJA 1999
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