AE Giuliano

C Colpaert

CB Teal

CE Cox

Christine B. Teal

DJ Dabbs

DP Cronin-Fenton

E Tousimis

M Colleoni

PD Gobardhan

Sameer Damle

English

PubMed

Springer - Publisher Connector

EDITORIAL
Can Axillary Lymph Node Dissection Be Safely Omitted
for Early-Stage Breast Cancer Patients with Sentinel Lymph
Node Micrometastasis?
Sameer Damle, MD and Christine B. Teal, MD, FACS
Department of Surgery, Breast Care Center, The George Washington University Medical Center, Washington, DC
This study presents data that we have been anxiously
awaiting. It adds to a slowly growing body of evidence that
axillary lymph node dissection (ALND) may be omitted in
select groups of node-positive patients. Many of us prefer
not to perform ALND when only micrometastases are
identified in sentinel lymph nodes (SLNs), especially when
it often involves returning to the operating room. It is
already the standard of care to omit ALND for patients who
have SLNs positive only by immunohistochemistry (IHC).
There are now tools available, such as the Memorial Sloan-
Kettering nomogram, that use tumor size, grade, number of
positive SLNs, method of detection, estrogen status, and
presence of lymphovascular invasion to determine the risk
of finding additional positive axillary nodes if ALND is
performed.1 Numerous studies have demonstrated a worse
prognosis associated with axillary micrometastasis.2–5
However, these studies are retrospective, and some evalu-
ated ALNDs performed before the era of routine SLN
biopsies. What is most interesting about this study is that it
prospectively evaluated the omission of ALND for
micrometastasis, and it has the longest follow-up available
in the literature for such patients.
Langer and colleagues demonstrate that patients with
tumors of \3 cm with micrometastatic foci 0.2–2 mm on
hematoxylin and eosin (H&E) stain or IHC have no worse
5-year survival than their node-negative counterparts,
despite the omission of a completion ALND. The node-
positive patients did not have axillary recurrences or distant
metastasis over a follow-up period ranging from 24–
106 months. From these data, the authors conclude that
ALND may be safely omitted in early stage breast cancer
patients with SLN micrometastasis. The conclusion that
ALND may be omitted in all early stage patients with
micrometastases, including those with high-grade tumors
[2 cm and with lymphovascular invasion, is perhaps
premature on the basis of their low numbers and short
follow-up. The American College of Surgeons Oncology
Group (ACOSOG) Z0010 and Z0011 studies will provide
more answers with larger numbers and longer follow up.
It is interesting to note that the authors found a 5-year
disease-free survival advantage in patients who were found
to have micrometastatic disease over node-negative
patients. Colpaert and colleagues found that the primary
tumor was an independent prognostic factor while axillary
micrometastasis were not, and they proposed that micro-
metastatic disease somehow primes the immune system,
allowing for a more robust response against further tumor
invasion.6 The 5-year overall survival in the study by
Langer and colleagues was equal in both groups.
The authors’ rate of finding micrometastasis in 12% of
their patients is consistent with the existing literature.7
However, this yielded only 27 patients, and approximately
half of these patients were positive by IHC. The authors do
not clarify whether the micrometastasis in the 13 patients
identified by IHC were subsequently identified by H&E,
which may affect their statistical analysis. Currently, many
surgeons will perform a completion ALND for microme-
tastases found by H&E, but not by IHC only. Cox and
colleagues have shown that these are two distinct patho-
logic processes with different prognostic implications.4
The authors may have had no choice but to combine the
two groups in order to provide enough patients to give their
study adequate power.
The fact that most (25 of 27) of the micrometastasis
were missed on frozen section is not surprising and
 Society of Surgical Oncology 2009
Published Online: 24 September 2009
C. B. Teal, MD, FACS
e-mail: cteal@mfa.gwu.edu
Ann Surg Oncol (2009) 16:3215–3216
DOI 10.1245/s10434-009-0702-3
parallels our experience. In our study evaluating scrape
cytology for intraoperative assessment of SLNs, 35% of
patients with negative SLNs intraoperatively were found to
have micrometastasis by serial H&E staining. Twenty
percent of the patients who went on to completion ALND
were found to have additional positive lymph nodes. In the
patients who elected against completion, there have been
no axillary or distant recurrences.8
There are some drawbacks to this study, which the
authors have acknowledged. The numbers are low, and
follow-up in some patients was as short as 24 months,
which is not long enough for evaluating recurrence or
survival. Although the authors state that their patients were
comparable in size, grade, location, and receptor status of
the tumor, as well as with chemotherapy and hormone
therapy regimens, some key differences are apparent. They
discuss a standard protocol where patients with micro-
metastatic disease were treated the same as node-negative
patients. However, three times as many node-positive
patients received combined hormone and systemic adju-
vant therapy, and they were more likely to receive adjuvant
therapy in general than node-negative patients (96% vs.
83%.) This could affect the disease-free and overall sur-
vival findings in this study.
The detection of micrometastasis in axillary lymph
nodes has steadily increased with the establishment of SLN
biopsy as the standard of care for staging the axilla. In
some studies, the incidence is reported to be as high as 23%
of patients with invasive breast cancer.7 A likely contrib-
uting factor is that pathologists are able to focus on fewer
nodes, thus allowing a more detailed examination.7 In
addition, the increasing use of IHC staining for H&E-
negative sentinel nodes results in further detection of
micrometastatic disease.2,9
With the increased detection of micrometastatic disease,
our management of such patients is becoming more
important. The larger numbers in the ACOSOG Z010 and
Z0010 trials will, we hope, allow for further subgroup
analysis to better account for confounding factors such as
lymphovascular invasion and tumor grade, as well as sep-
arate the pN1mic from the pN0i? patients. This would
certainly provide more reassurance to surgeons who are
considering avoiding ALND in patients with positive
SLNs. So unfortunately, the answer to the question about
whether ALND can safely be omitted for all early-stage
patients with micrometastasis is, we don’t know yet, but we
hope so.
REFERENCES
1. Tousimis E, Van Zee KJ, Fey JV, Hoque L, Tan LK, Cody HS,
et al. The accuracy of sentinel lymph node biopsy in multicentric
and multifocal invasive breast cancers. J Am Coll Surg.
2003;197:529–35.
2. Gobardhan PD, Elias SG, Madsen EVE, Bongers V, Ruitenberg
HJM, Perre CI, et al. Prognostic value of micrometastases in
sentinel lymph nodes of patients with breast carcinoma: a cohort
study. Ann Oncol. 2009;20:41–8.
3. Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Mazzarol
G, Pruneri G, et al. Size of breast cancer metastases in axillary
lymph nodes: clinical relevance of minimal lymph node involve-
ment. J Clin Oncol. 2005;23:1379–89.
4. Cox CE, Kiluk JV, Riker AI, Cox JM, Allred N, Ramos DC, et al.
Significance of sentinel lymph node micrometastases in human
breast cancer. J Am Coll Surg. 2007;206:261–8.
5. Dabbs DJ, Fung M, Landsittel D, McManus K, Johnson R.
Sentinel lymph node micrometastasis as a predictor of axillary
tumor burden. Breast J. 2004;10:101–5.
6. Colpaert C, Vermeulen P, Jeuris W, Van Beest P, Goovaerts G,
Weyler J, et al. Early distant relapse in node-negative breast cancer
patients is not predicted by occult axillary lymph node metastases,
but by the features of the primary tumour. J Pathol. 2001;139:
442–9.
7. Cronin-Fenton DP, Ries LA, Clegg LX, Edwards BK. Rising
incidence rates of breast carcinoma with micrometastatic lymph
node involvement. J Natl Cancer Inst. 2007;99:1044–9.
8. Teal CB, Tabbara S, Kelly T. Evaluation of intraoperative scrape
cytology for sentinel lymph node biopsy for patients with breast
cancer. Breast J. 2007;13:155–7.
9. Giuliano AE, Dale PS, Turner RR, Morton DL, Evans SW, Krasne
DL, et al. Improved axillary staging of breast cancer with sentinel
lymphadenectomy. Ann Surg. 1995;222:394–9.
3216 S. Damle, C. B. Teal


Can Axillary Lymph Node Dissection Be Safely Omitted for Early-Stage Breast Cancer Patients with Sentinel Lymph Node Micrometastasis?

Crossref

Indian Journal of Surgical Oncology

Early distant relapse in node-negative breast cancer patients is not predicted by occult axillary lymph node metastases, but by the features of the primary tumour.

Evaluation of intraoperative scrape cytology for sentinel lymph node biopsy for patients with breast cancer.

Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg.

Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study. Ann Oncol.

Rising incidence rates of breast carcinoma with micrometastatic lymph node involvement.

Sentinel lymph node micrometastasis as a predictor of axillary tumor burden.

Signiﬁcance of sentinel lymph node micrometastases in human breast cancer.

Size of breast cancer metastases in axillary lymph nodes: clinical relevance of minimal lymph node involvement.

The accuracy of sentinel lymph node biopsy in multicentric and multifocal invasive breast cancers.

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Can Axillary Lymph Node Dissection Be Safely Omitted for Early-Stage Breast Cancer Patients with Sentinel Lymph Node Micrometastasis?

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