Original Study

Surgical Staging of the Axilla: Is It on Its Way

Out? A Retrospective Study and Review of
the Literature
Debkumar Chowdhury, Ionela Drehuta, Sanjeet Bhattacharya
Abstract
Sentinel lymph node biopsy (SLNB) has long been the mode of staging of the axilla in invasive breast cancer.
We studied the incidence of axillary disease in patients with ultrasound negative axilla in a selected group of
patients. We noted that the false negative rate of axillary ultrasound and SLNB was comparable in a subset of
early breast cancer patients.
Introduction: Sentinel lymph node biopsy (SLNB) is the reference standard for axillary staging in all patients with
invasive breast cancer. Surgical practices are being reviewed for a more conservative approach to the axilla. Patients
and Methods: In this audit, we studied the incidence of axillary disease in patients with ultrasound negative axilla. The
selection criteria are similar to an ongoing national study: female patients, age > 50 years, primary breast lesion < 1.5
cm in size, and estrogen receptorepositive and HER-2 (human epidermal growth factor receptor 2)-negative disease.
We studied the data of all breast cancer patients, January 2013 to December 2015, in a population of 350,000 with
annual incidence of about 400 cancers. Results: In our patient subset, we studied a total of 261 patients. The average
false-negative (FN) rate with axillary ultrasound (AUS) per year was noted to be 10.7% (P .0052). This is comparable
to SLNB, which has a FN rate of approximately 10%. The sensitivity of AUS to exclude axillary disease was 89.3%
(95% condence interval, 84.9-92.3). Conclusion: Because the FN rate of AUS and SLNB are comparable, the former
can possibly replace the latter, at least in a subset of early breast cancer patients. This nding has wide implications.

Clinical Breast Cancer, Vol. -, No. -, --- Crown Copyright 2017 Published by Elsevier Inc. All rights reserved.
Keywords: Axillary treatment, Axillary ultrasound, Breast cancer, False negative rate, Sentinel lymph node biopsy

Introduction
Surgery for breast cancer has signicantly advanced through the
years. There has been particularly growing interest in surgery in the
axilla with review of current practices. In the past, axillary lymph node
dissection (ALND) was the preferred mode of surgical staging of the
axilla. Sentinel lymph node biopsy (SLNB) has been the cornerstone of
surgical staging of the axilla in patients with breast cancer, including
those with negative axillary ultrasound (AUS) in early breast cancer
patients. The technique was rst described in 1989,1 and since then, it
has been gradually incorporated into practice. SLNB is thought to have
a high overall accuracy in detecting disease in the axilla, with estimates of
93% and 97%, and a low false-negative (FN) rate of 9.8%.2-5
SLNB has fewer associated patient comorbidities compared to
ALND. There have been a series of randomized controlled trials6,7
Department of General Surgery, University Hospital Ayr, Ayr, Scotland, United Kingdom
Submitted: Apr 26, 2017; Accepted: May 14, 2017
Address for correspondence: Debkumar Chowdhury, MBChB, PGCert (HPE), Depart-
ment of General Surgery, University Hospital Ayr, Ayr, Scotland, United Kingdom
E-mail contact: dc7740@my.bristol.ac.uk
that have studied the role of surgery on the clinically negative axilla.
The results from these trials have supported the cause for the change
in clinical practice toward reduced rates of axillary dissection and
have instead suggested the use of axillary radiation as an alternative
to dissection in a cohort of patients. One such progressive trial is
ALLIANCE A011202, in which residual disease is detected
comparing ALND with axillary radiotherapy in patients who
received chemotherapy. AUS is being considered as an alternative to
the widely prevalent SLNB in detecting disease in the axilla,
depending on the size and type of the lymph nodes in the axilla.
There has been debate over the use of ALND in patients with
SLNB-positive ndings. A large number have no further positive
nodes. All positive nodes are removed in SLNB.
The POSNOC trial8 looked at the role of axillary treatment in
patients with 1 or 2 sentinel nodes with macrometastases. This
was studied in both breast-conserving surgery and mastectomy
patients. The aim of the trial was to assess whether adjuvant
therapy alone is no worse than adjuvant therapy plus axillary
treatment in terms of axillary recurrence within 5 years in women
with early-stage breast cancer with 1 or 2 sentinel node
macrometastases.

1526-8209/$ - see frontmatter Crown Copyright 2017 Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.clbc.2017.05.005 Clinical Breast Cancer Month 2017 -1
 Surgical Staging of the Axilla
The POSNOC trial was inuenced by the results from the Z11
trial. One of the main differences between the POSNOC trial and
the Z11 trial was that in the POSNOC trial, women who had
undergone mastectomy would be eligible. The other difference was
that for the POSNOC trial, axillary ultrasound was mandatory.
The Z11 trial studied whether it was benecial for patients to
undergo ALND in patients with disease in sentinel nodes.9 The
women included in the Z11 trial were treated by breast-conserving
surgery and whole-breast radiotherapy with 1 or 2 sentinel node
metastases. These patients were randomized to receiving ALND or
not. The results from the study found that there was no difference
between patients with ALND and no ALND in relation to axillary
disease recurrence and survival.
There is a nationwide study looking at the use of AUS and
comparing the rates of FN with that achieved with SLNB. This was
inuenced by the results from the successful completion of the pilot
phase of a 2016 randomized controlled trial comparing SLNB to no
further axillary staging in patients with early breast cancer with
negative ultrasound.10 The authors provided prospective evidence
through the published results supporting the use of AUS to exclude
clinically signicant disease in the axilla and thereby to undertake a
phase 2 randomized controlled trial studying the same. We wanted
to investigate the rates of FN AUS cases within our NHS Trust
based across our sites, University Hospital Ayr and University
Hospital Crosshouse Hospital. Our secondary aim was to study the
economic impact and the potential savings that could be made in
the light of fewer axillary procedures.
Methods
In this audit, we studied the incidence of axillary disease in patients
with an ultrasound-negative axilla. We retrospectively studied the
prospectively collected data of all breast cancer patients from January
2013 to December 2015 in a population of 350,000 within NHS
Ayrshire and Arran, with an annual incidence of approximately 400
cancers. The selection criteria were similar to the criteria used in the
currently carried out national study. They included the following:
female patients, age > 50 years, primary breast lesion < 1.5 cm, and
estrogen receptorepositive and HER-2 (human epidermal growth
factor receptor 2)-negative disease. In this study, we looked into the
FN rates of AUS in early breast cancer. We also studied the cost of the
procedure and the potential savings that could be made in the already
cash-strapped National Health Service (NHS).
Results
Within our patient subset, we identied a total of 261 patients over
the 3 years (Table 1). We calculated the FN rates over the years and
established this to be 10.7% (28/261). This is well comparable to
Table 1 Breakdown of Cases by Year
Year No. Total Cases
2013 378
2014 404
2015 376
Average percentage false-negative ndings through 3 years is 10.7% (P .0052).
2 - Clinical Breast Cancer Month 2017
SLNB, which has a FN rate of approximately 10%. Although SLNB
is highly sensitive in detecting axillary disease, it is associated with a
number of potentially avoidable complications, including arm lym-
phoedema, arm pain, and reduced shoulder function. De Groef et al11
reported an 8% chance of developing lymphoedema and an even
greater chance of developing arm pain and reduced function on the
ipsilateral side. The rates of lymphoedema after SLNB can be vari-
ablebetween 0% and 63%, as reported by a systematic review.12
We also studied the cost of performing SLNB in the NHS setting
and found it to be approximately 400 per procedure, including the
cost of equipment. In our subset of early breast cancer patients,
SLNB could be avoided in 233 cases; this would potentially have led
to savings of approximately 93,200 over 3 years (Table 2). This
may be an oversimplication from a retrospective analysis of the
potential savings that could have been made.
Taking our results into consideration, the sensitivity of AUS to
exclude axillary disease was 89.3% (95% condence interval, 84.9-
92.3). This is comparable to other, larger studies, such as the meta-
analysis conducted by Houssami et al.13
Discussion
Through the decades, there has been extensive research and renewed
interest in detecting disease in the axilla. Historically, the mainstay of
axillary surgery was axillary node clearance in clinically positive axilla,
whereas in clinically negative axilla, axillary node sampling was the
norm. Researchers are investigating the use of localized radiotherapy in
patients with a few positive nodes in the axilla within a select criterion.
This would potentially avoid any surgical intervention in the axilla and
hence reduce development of complications.
Regarding the sensitivity of AUS in detecting axillary disease, a
2011 meta-analysis conducted by Houssami et al13 established this
to be approximately 79.6%, with a specicity of 98.3%. The
ASOCOG Z0011 trial was perhaps one of the most important
trials; it garnered much interest in breast surgeons.14 This ran-
domized controlled trial compared survival in patients receiving
axillary dissection with those not receiving axillary dissection in
patients with disease-positive sentinel nodes. It was interesting to
note that in patients with limited sentinel lymph node involvement
treated with conservation surgery and systemic therapy, use of
sentinel lymph node dissection alone compared to ALND and did
not result in inferior survival. Studies are currently being carried out
comparing the use of nonsurgical management in patients with
limited sentinel lymph node disease and those receiving axillary
radiotherapy. The result of these studies could transform current
surgical practice. It has also been noted that the rates of locoregional
occurrences of axillary disease in patients with negative SLNB is
between 0.5% and 1.5%.15-17
Percentage of Positive
No. Cases With Criteria No. Positive Nodes Nodes Falsely Negative
69 5 7.24
118 17 14.4
74 6 8.10

Table 2 Potential Savings Each Year
No. Extra Cases Potential
Year Potentially Avoided Savings ()
2013 64 25,600
2014 101 40,400
2015 68 27,200
Average savings potentially made per year is 31,066.
A meta-analysis of 30 studies studying patients with positive
SLNB and without complete axillary dissection was reviewed. In
these patients, there was evidence of micrometastatic disease in
SLNB. It was noted that the rate of axillary recurrence was 0.3%
after 42 months of follow-up.18 Other studies have shown the rates
of axillary recurrence to be < 1%. The preliminary results from the
RAS SNAC (sentinel node vs. axillary clearance) trial also support
this proposition.19 This centrally randomized phase 3 clinical trial
based in Australasia compares SLNB with axillary clearance in
women with early breast cancer. It also determines if SLNB pro-
duces less morbidity and comparable cancer-related outcomes,
thereby suggesting that complete axillary dissection may not be as
potentially benecial as previously thought. This has led researchers
to believe that patients with certain favorable characteristics ought
not undergo axillary node dissection, even with positive SLNB.
These characteristics include smaller tumor size and lower tumor
grade.
Conclusion
Our study highlighted the fact that the FN rates with AUS are
comparable to that of SLNB in the clinically negative axilla in pa-
tients with early breast cancer. Our study adds to a growing
consensus among breast surgeons that AUS is comparable to SLNB
in clinically negative axilla in patients with early breast cancer. This
would have a signicant impact on our patients lives and on the
already cash-strapped NHS. This would translate into fewer axillary
procedures; the extent of patient morbidities would also be minimal.
This would greatly affect resource use as well. We await the out-
comes of the highly promising ALLIANCE A011202 trial; its re-
sults could potentially pave the way for even fewer axillary
procedures, even in a subset patient with axillary disease. In terms of
nancial savings, our analysis indicated a potential saving of
93,200 over a period of 3 years. Once we have amalgamated all the
results from the nationwide trials, a paradigm in surgical practice is
likely to be put into place.
Clinical Practice Points
 Sentinel lymph node biopsy (SLNB) has been the main modality
of surgical staging of the axilla in patients with invasive breast
cancer.
 There has been growing interest among breast clinicians to
modify their approach to the axilla in the view of fewer surgical
procedures to the axilla.
 There are already large studies such as the Z11 and the POS-
NOC trial which support fewer axillary procedures in a subset of
patients.
Debkumar Chowdhury et al
 Through our study, we highlighted that the false negative rate of
axillary ultrasound was comparable to sentinel lymph node bi-
opsy in a subset of early breast cancer patients.
 Once we have amalgamated all the results from the nationwide
trials, a paradigm in surgical practice is likely to be put into place.
Acknowledgment
We thank the breast care teams at University Hospital Ayr and
University Hospital Crosshouse.
Disclosure
The authors have stated that they have no conict of interest.
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