Should Intraoperative Frozen Section Evaluation of Breast Lumpectomy Margins Become Routine Practice?
Am J Clin Pathol
Should Intraoperative Frozen Section Evaluation of Breast Lumpectomy Margins Become Routine Practice?
Stuart J. Schnitt
Monica Morrow
635 635
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In this issue of the Journal, Jorns et al1 report that
intraoperative frozen section examination of breast lumpectomy
margins was associated with a substantial reduction in the
rate of reexcision. In their retrospective study, at some time
after the initial lumpectomy a reexcision was performed in
48.9% of patients who did not have frozen section margin
evaluation compared with only 14.9% of those in whom
frozen section evaluation of the margins was performed.
Further, these investigators developed a technique to overcome
the methodological difficulties of attempting to cut frozen
sections of fatty tissue such as margins of breast specimens.
So if it is now technically feasible to obtain adequate frozen
sections from lumpectomy margins and if intraoperative
frozen section evaluations of these margins can reduce the
need for a subsequent reexcision by almost 70%, should
pathologists the world over be gearing up to routinely freeze
margins of breast lumpectomy specimens? To answer this
question, we must first review some fundamental data on
lumpectomy margins and their association with local
recurrence, and put these data into current clinical context.
Various patient factors, treatment factors, and
pathologic factors have been reported to be associated with an
increased risk of recurrence in the ipsilateral breast (local
recurrence) after breast-conserving treatment for invasive
breast cancer and ductal carcinoma in situ (DCIS).
Arguably the most important of these is the status of the
microscopic margins of excision of the resected breast specimen.
Positive margins (ie, invasive carcinoma or DCIS at an
inked tissue edge) have consistently been associated with
a higher risk of local recurrence than negative margins.2
Therefore, obtaining negative margins is the primary goal
of breast-conserving surgery. Unfortunately, there is far
from universal agreement as to what constitutes an adequate
negative margin. In fact, results of surveys of surgeons
and radiation oncologists have demonstrated that no single
margin width is considered adequate by more than 50%
of respondents. When 318 surgeons were presented with a
scenario involving a patient with a T1 invasive breast cancer
with planned radiation therapy after lumpectomy, 11%
indicated that tumor not touching ink was an adequate negative
margin, 42% favored a margin of 1 to 2 mm, 28% favored
a margin of 5 mm or more, and 19% preferred a margin of
more than 10 mm.3 In a survey of 730 surgeons in Canada,
40% considered a margin negative for invasive breast cancer
if there was no tumor at ink, 14% required a 1-mm margin,
29% a 2-mm margin, and 18% a 5-mm margin. A similar
pattern was seen among patients with DCIS.4 Finally, in a
survey of 702 North American radiation oncologists, 45.9%
considered a margin negative when there was no tumor at
the inked margin; margins of 1 mm, 2 mm, 3 mm, 5 mm,
and 10 mm were considered negative by 7.4%, 21.8%, 10%,
10% and 4.9% of respondents, respectively.5
Lack of agreement among clinicians as to what
constitutes an adequate negative margin has led to wide variation
in the rate of reexcision after lumpectomy. In a recent study
that included 54 surgeons, rates of reexcision ranged from 0%
to 70%.6 Further, approximately half of all reexcisions are
performed in patients with negative margins in the belief that
a wider negative margin will further decrease the rate of local
recurrence. The effect of frozen section examination on
reducing reexcision rates will be highly dependent on the baseline
rate of reexcision (ie, the benefit will be greater when the
baseline reexcision rate is high, as in the study of Jorns et al1
in which the baseline rate of reexcision was almost 50%) and
whether reexcision is routinely performed to achieve some
arbitrary negative margin width beyond tumor at the inked
tissue edge, as seen in the study of Jorns et al.1
However, do millimeters really matter when it comes
to lumpectomy margins? The results from retrospective
studies have not consistently demonstrated that
increasing margin widths in millimeter intervals in the 1-mm to
5-mm range results in a significant reduction in the risk of
local recurrence among patients with invasive breast cancer
treated with breast-conserving surgery and radiation therapy.
Moreover, a metaanalysis of 21 retrospective studies that
examined the influence of margin width on local recurrence
in more than 14,500 patients failed to identify a statistically
significant difference in local recurrence rates associated
with margin widths of more than 1 mm, more than 2 mm, or
more than 5 mm after adjustment was made for the use of a
radiation boost or adjuvant systemic therapy.2
It should not be surprising that it has been difficult to
demonstrate that millimeters matter with regard to
negative margin width, given (...truncated)