1. CME Topic
Surgical Margins in Breast Conservation
Therapy: How Much Should We Excise?
Tsz Ting Law, MBBS, and Ava Kwong, FRCS
some authors to obtain good results in terms of LR although
Background: Breast conservation therapy (BCT) has become the
standard of treatment for early stage breast cancer, and the surgical
others would accept a much smaller margin.
margin was one of the important factors that affected risk of local
recurrence. This review looks at the safe margin for BCT in early stage Margins for Invasive Breast Cancer
invasive breast cancer and ductal carcinoma in situ (DCIS). The definition of a free margin varies. According to the
National Surgical Adjuvant Breast and Bowel Project
Methods: Published literature abstracted in Medline was searched (NSABP),2 a margin is positive if tumor cells are present at
using the gateway site from the US National Library of Medicine. the edge of resection on inked histology section. Quadrante-
Conclusions: A positive margin is associated with increased risk of ctomy described in the Milan trial involved excision of 2–3
local recurrence after BCT for invasive breast cancer and DCIS. How- cm of normal tissue around the tumor7; the European Orga-
ever there was no cut off for the margin width and the significance of nization for Research and Treatment of Cancer (EORTC) trial
a close margin remains controversial. It was generally accepted that the considered 1 cm gross as free margin.8
risk of local recurrence was low if the margin was 10 mm while There was no quantitative definition of a negative margin in
margins that were 2 mm were considered inadequate. The surgeon some studies,9,10 while others quantitatively defined negative
needs to balance the risk between local recurrence and cosmesis in margin as no tumor cells within a fixed distance of the cut edge
planning BCT so that the prognosis is not compromised. of the surgical specimen, for example, 1 mm, 2 mm, 3 mm, and
so forth.11,12 Controversies exist in the literature regarding the
Key Words: breast conservation therapy, local recurrence, surgical meaning of a close margin. In general a close margin is defined
margin as cancer cells being within 1 mm of the inked margin.
The majority of studies show that positive margins result
W ith the increasing use of screening mammography, the
majority of breast tumors are detected when they are
small. Breast conservation therapy (BCT), which includes
in an increased rate of LR. A review by Singletary13 showed
that patients with positive margins had increased incidence of
LR with increasing follow-up times, using 2 mm as a nega-
local excision and radiation treatment to the breast, has be- tive margin. When studies were grouped according to how
come the treatment standard for early invasive breast cancers the negative margin was defined (ie positive versus negative,
(stages I & II).1,2 The rate of local recurrence (LR) following 1 mm and 2 mm, respectively), the differences in LR between
BCT varies between 5 and 10%.1,2 Surgical margin status is positive and negative margins were highly significant for
considered to be one of the factors which increases risk for each group. For a negative margin defined as 1 mm, LR
LR, and to date there is no consensus on a safe margin. was 3–7% in negative margin group versus 16 –22% in the
Margins for Ductal Carcinoma In Situ positive margin group; whereas the negative margin was de-
BCT is an established treatment for ductal carcinoma fined as 2 mm, LR was 2–7% versus 8 –22% in the two
in-situ.3– 6 A wide margin up to 10 mm had been suggested by
From the Division of Breast Surgery, Department of Surgery, The University Key Points
of Hong Kong Li Ka Shing Faculty of Medicine, Queen Mary Hospital, • There is no cut off regarding a safe margin width for
Hong Kong SAR. breast conservation therapy in the literature.
Reprint requests to Dr. Ava Kwong, Chief of Breast Surgery Division, Department • It is generally accepted that the risk of local recur-
of Surgery, The University of Hong Kong Li Ka Shing Faculty of Medicine,
Queen Mary Hospital, Hong Kong SAR. Email: avakwong@hkucc.hku.hk rence is low if the margin is 10 mm while margins
Neither Dr. Law or Dr. Kwong have any disclosures to declare or conflicts 2 mm are considered inadequate.
of interest to report. • The surgeon needs to balance the risk between local
Accepted July 10, 2009. recurrence and cosmesis in planning breast conserva-
Copyright © 2009 by The Southern Medical Association tion therapy so that prognosis is not compromised.
0038-4348/0 2000/10200-1234
1234 © 2009 Southern Medical Association

2. CME Topic
groups, respectively.13 However, in examining the LR rates mammography; as a result, a wide margin is recommended
in patients with negative margin, no clear cut differences for excision. Randomized controlled trials, namely NSABP
based on the exact margin width were found. Whether pa- B-17,3 UKCCCR,6 and EOTRC 108534,5 showed that BCT
tients with close margin had a LR rate equivalent to those followed by radiotherapy reduced the risk of noninvasive and
with a positive margin, negative margin, or intermediate mar- invasive recurrences in the ipsilateral breast when compared
gin was unclear. with local excision alone. The incidence of invasive ipsilat-
eral breast recurrence in patients who received radiotherapy
Margins for DCIS was 3.9% and 5.8% at 5 yrs in NSABP B-17 trial and EORTC
DCIS is a local disease lacking stromal invasion and 10853 trial, respectively, which was lower than the excision
distant metastases. The presentation varies from a palpable group. Data from the pathological review of NSABP B-17
mass to microcalcifications on mammography. The work by and EORTC 10853 trials showed that the risk of LR was
Holland showed that the histological size of DCIS might not higher in patients who did not have free margins.5,16 Unfor-
correlate with mammographic findings.14,15 The reliability of tunately, the trial eligibility criteria did not require reporting
mammography in assessing tumor size was related to both the of margin widths in all 3 trials. Only 5% of the pathological
histological type and the type of microcalcifications seen on reports did specify the exact distance in the EORTC trial.4,5
Table 1. Summary of reported rates of local recurrence after breast-conserving therapy for ductal carcinoma in
situa
Author Margin (mm) N Management LR (%) Follow-up (mo) Conclusion
Silverstein23 10 mm 93 Excision 2.2 Mean 81 No reduction in probability of LR with addition of
postop RT if margin is 10 mm
10 mm 40 Excision RT 2.5 — —
Kestin24 2b 44 Excision RT 5.9 Median 84 Margin status alone may not predict complete tumor
extirpation adequately
2 88 Excision RT 15.1 — —
Chan17 1 66 Excisionc 37.9 Median 47 Margins greater than 1 mm regardless of width of
clearance was associated with a low LR
1.1–5 89 — 3.5 — —
5.1–10 28 — 7.1 — —
10 22 — 4.5 — —
Vicini25 2 46 Excision RT 11.0 Median 87 Margin status alone may be suboptimal in accurately
defining excision adequacy
2 99 Excision RT 2.0 — —
Vargas21 2 34 Excision 13.0 Median 73 Margins 2 mm are shown to be an independent
predictor of LR
2 198 Excision 4.0 — —
MacDonald22 0 (transected) 32 Excision 46.7 Median 57 Margin width is the single most important factor in
predicting LR after excision alone for DCIS
0.1–0.9 53 Excision 34.0 — —
1.0–1.9 20 Excision 35.0 — —
2.0–2.9 82 Excision 24.4 — —
3.0–5.9 39 Excision 20.5 — —
6.0–9.9 22 Excision 9.1 — —
10 197 Excision 4.6 — —
MacDonald18 10 212 Excision 5.7 Median 53 Low risk of LR after excision alone for DCIS with
margins 10 mm
10 60 Excision RT 1.7 — —
West19 5 82 Excision RT 1.4 Median 97 5 mm margin plus radiation results in low rates of
recurrence
10 71 Excision 6.0 — —
a
RT, radiotherapy; LR, local recurrence; DCIS, ductal carcinoma in situ.
b
Includes uncertain margin (n 3).
c
Majority of patients received excision only, other patient received adjuvant radiotherapy tamoxifen.
Southern Medical Journal • Volume 102, Number 12, December 2009 1235

3. Law and Kwong • How Much Should We Excise?
As a result a “safe” margin could not be concluded from these Table 2. Intraoperative margin assessment techniques
studies. Nevertheless, margin status was consistently found to
be an important risk factor for recurrence in many nonran- Advantages Disadvantages
domized trials. There was a low risk of recurrence after ex-
Gross evaluation Rapid Gross evaluation only
cision alone for DCIS with surgical margins of more than 10 of specimen
mm,17–19 whereas a close margin ( 2 mm) was associated Pathologic
with an increase risk of residual disease. The study of residual evaluation
DCIS in re-excision specimens showed that initial excision Frozen section Accurate Loss of tissue
margin significantly predicted for residual tumor in re-exci- Histologic artifacts
sion specimens.20 Margin status was shown to be an inde- related to tissue
preparation
pendent predictor of LR.21 Results from a retrospective study
Increased operation time
of 445 patients with pure DCIS treated by excision alone
Touch Rapid Could not assess close
indicated that margin width was the most important indepen- preparation margin
dent predictor of LR.22 cytology No tissue loss Cytopathology training
It is not clear whether there is a subgroup of low risk Imaging
patients who do not require radiotherapy. Silverstein et al23 Intraoperative Real time Limited role in
showed that excellent local control was achieved in a sub- ultrasonography Performed by surgeon nonpalpable lesions
group of patients with margin widths of 10 mm or greater Specimen Assessed margin in Time consuming
with excision alone and hypothesized that radiation did not radiography nonpalpable lesions
have significant benefit in this group of patients.
Besides margin status, a number of clinical and patho-
logical factors for recurrences include patient age, nuclear
and slides reviewed by cytopathologists. Early results were
grade, histologic type and the presence of necrosis; they must
promising.33,34 Intraoperative ultrasound showed significant
be added into consideration in the clinical management.24,25
reduction of pathologically positive margins in palpable tu-
The Van Nuys prognostic index (VNPI) is a tool that quan-
mors.35 Specimen radiography was mandatory for resection
tifies 4 measurable prognostic factors: tumor size, margin
of nonpalpable lesions.36
width, nuclear grade, and the presence or absence of come-
donecrosis.26 A fifth factor, patient age, was added by inves-
tigators from the University of South California (USC) and Oncoplastic Surgery
became the USC/VNPI.27 Patients are stratified into different The balance between oncological control and cosmetic
risk groups for LR according to the score with the aim of outcome is always a concern in BCT. The use of plastic
aiding clinical decision making. The validity of VNPI needs surgery techniques following lumpectomy, “oncoplastic sur-
to be further confirmed by other groups. Table 1 summarizes gery,” is widely practiced in Europe.37 The margin of exci-
the LR rate after BCT in DCIS using different margin cutoffs. sion is frequently wider as the tumor is removed en bloc with
the tissue removed for mammoplasty.37 Short term oncolog-
ical results in terms of LR and distant metastases is compa-
Management of Positive Margin rable with the results of BCT randomized trials,38,39 yet long
For both invasive breast cancer and DCIS, re-excision(s) term oncological safety needs further investigation.
was recommended for positive margins in order to reduce the
risk of LR.28 Treatment options for patients with close or focally Conclusion
positive margins should be individualized as the chance of hav- A positive margin is associated with increased risk of LR
ing significant residual tumor is not high.29 Personalized radio- after BCT for invasive breast cancer and DCIS. There is no
therapy is the treatment of choice in some centers.30 cut off for the margin width and the significance of a close
margin remains controversial.40,41 The surgeon needs to bal-
Intraoperative Assessment of Margin Status ance the risk between LR and cosmesis in planning BCT so
Intraoperative margin assessment techniques are de- that prognosis is not compromised.
scribed in Table 2. Staining could be used to stain the entire
cut surface of the specimen, with placement of one or more References
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1236 © 2009 Southern Medical Association

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