Experts debate how to achieve both clear margins and the best cosmesis
Introduction
Anees B. Chagpar, MD, MSc, MA, MPH, FACS, FRCS(C)
Breast Center—Smilow Cancer Hospital at Yale-New Haven and Yale University School of Medicine
In a past column on ASCOconnection.org, I talked about a debate that
had occurred in our tumor board in which a patient had a margin <1 mm
from ink. While “technically negative,” it was a little too close for
comfort for me; the surgeon whose case it was, however, argued based on
evidence from the NSABP B-06 trial that if a tumor did not touch ink,
outcomes were equivalent to the alternative of mastectomy—at least for
survival. It brought up how we interpret data—and the difference between
what we know and what we think we know; or as the comedian Stephen
Colbert would put it, between “truth” and “truthiness.” We like to think
that what we do is “evidence-based,” but we can almost always
find data to support any position we wish to take.
My two good friends, Dr. Mel Silverstein and Dr. Mike Dixon, have
duked out the margins debate in many public forums and settle the score
here once and
for all. Here is what we know for sure: (1) obtaining negative margins
reduces local recurrence rates; (2) there is no consensus on what
constitutes an adequate negative margin (although many would be happy
with >1 mm); (3) radiation therapy continues to play a role in
breast-conserving surgery (
although there may be exceptions in tiny
areas of estrogen receptor-positive ductal carcinoma in situ excised
with widely clear margins); (4) there are ways to take out large segments of breast tissue without compromising cosmesis (
although taking out less may yield excellent cosmetic outcomes without needing a contralateral symmetry procedure); and finally, (5) for the record, Mel is not a Republican (
not that it matters).
Dr. Chagpar is Director of the Breast Center at Smilow Cancer
Hospital, Assistant Director for Diversity and Health Equity at Yale
Comprehensive Cancer Center, Program Director of the Yale
Interdisciplinary Breast Fellowship, and an Associate Professor in the
Department of Surgery at Yale University School of Medicine. She
currently serves on ASCO’s International Affairs Committee and is a
columnist for ASCOconnection.org.
Less Is More
J. Michael Dixon, BSc, MBChB, MD, FRCS, FRCS(Ed), FRCP(Hon)
Western General Hospital Edinburgh
More than 20 years after randomized trials demonstrated that
breast-conserving surgery followed by post-operative radiotherapy has
the same outcome as mastectomy, there still remains controversy as to
how much of the breast should be excised when performing
breast-conserving surgery. The aim of breast-conserving surgery is to
excise the cancer to clear margins.
1,2
The controversy surrounds what constitutes a clear margin. The margin
width is the distance from the cancer to the ink painted on the surface
of the excision specimen. In surveys of surgeons and radiation
oncologists, no one margin width was endorsed by more than 50% of
respondents.
3-5 Thus, there is no consensus, and one
consequence of this is that given a distance to the nearest margin of 1
mm, some surgeons and oncologists will accept this whereas others advise
re-excision to achieve a wider margin.
A major problem in the published literature is that there are large
numbers of single-center series that have all used different margin
widths to define what constitutes complete excision.
6 This allows any individual surgeon to quote a paper that supports his or her personal view.
The first review of surgical margins was conducted by Eva Singletary, MD, and published in the
American Journal of Surgery in 2002.
7
What Dr. Singletary established was that leaving disease at margins was
unacceptable and significantly increased local recurrence rates. She
established that wider margins did not reduce local recurrence rates and
concluded that some of the best local recurrence rates were in series
that had used a 1- to 2-mm margin width. This was endorsed by a more
recent comprehensive review and meta-analysis of 21 retrospective
studies.
8 This analysis included 14,571 patients with breast
cancer and demonstrated that a positive margin was associated with an
odds ratio for local recurrence of 2.42. If the margin width was <1
mm this increased local recurrence by 1.8 times. There was, however, no
statistical difference in local recurrence rates associated when
comparing margin widths of >1 mm, >2 mm, and >5 mm when studies
were adjusted for the use of radiation boost and endocrine therapy. The
finding of this comprehensive meta-analysis was that a 1-mm negative
margin is as good as a wider margin if patients receive optimal adjuvant
therapy. The conclusion was that there is no justification for
demanding margins greater than 1 mm.
Some have found difficulty in believing that recurrence rates are not
reduced when margins are wider. This is in part because detailed
whole-breast studies have shown disease extending 2 to
3 cm from the edge of the primary
cancer.
9 What a “clear 1-mm margin”
indicates is not that there is no residual disease in the breast, but
that any residual tumor burden is low and will be controlled with
radiotherapy. Although mastectomy is offered to many patients, and
patients choose it in the belief that this reduces local recurrence
rates, mastectomy does not eliminate local recurrence. Randomized trials
comparing mastectomy alone with breast-conserving surgery and
radiotherapy have in fact shown similar local recurrence rates with both
breast-conserving surgery followed by radiotherapy and mastectomy.
10
Systemic treatment reduces local recurrence
The rates of local recurrence after breast-conserving surgery continue to fall.
8
In NSABP B-06, the 20-year recurrence rate was 14.3%,1 whereas the
NSABP trials conducted in the 1990s showed 10-year local recurrence
rates ranging between 3.5% to 6.5%.
11 One of the major
reasons for this is that systemic treatment reduces local recurrence
significantly. In-breast recurrence was reduced in NSABP B-14 from 14.7%
in the placebo group to 4.3% in patients receiving tamoxifen,
12
and in NSABP B-13, which included patients with ER-negative tumors,
there was a 10-year recurrence rate of 13.4% in the no-treatment group
compared with 2.6% in patients receiving chemotherapy.
13
Studies from Edinburgh in more than 1,300 patients have confirmed that
local recurrence rates do not fall with increasing margin width. In
breast tumors, recurrence rates also did not increase when front and
back margins were less than 1 mm, provided that full thickness of breast
tissue was taken and radiotherapy boost was delivered. There were in
fact no local recurrences at five years in patients who had a positive
deep margin even though pectoral fascia was not removed routinely.
Importance of cosmetic outcome
It is important to limit the amount of breast tissue removed during
breast-conserving surgery because the single most important factor
affecting cosmetic outcome is the volume of breast tissue removed.
14
Wider excisions remove more tissue and so produce significantly poorer
cosmetic outcomes. There is a direct correlation between cosmetic
outcome and psychological well-being—anxiety and depression scores, body
image, sexuality, and self-esteem are reported as being significantly
better in patients with excellent or very good cosmetic results; only
patients who get a good cosmetic outcome gain the full benefits of
breast-conserving surgery.
15
The evidence shows that wider margins
have no benefit in breast-conserving surgery. Wider margins have an
adverse effect on the cosmetic outcome. Surgeons must abandon their
obsession with wide margins and accept 1 mm as sufficient. Such a change
will reduce health care costs, reduce the number of women having
re-excisions, improve cosmetic outcomes, and thus significantly benefit
patients.
Dr. Dixon is a Professor of Breast Surgery and Consultant
Surgeon, Edinburgh Breast Unit, Western General Hospital Edinburgh, UK.
He currently serves on the editorial boards of Breast Cancer Management
and Annals of Surgical Oncology and is Co-Chair of the Miami Breast
Cancer Conference.
References
-
Fisher B, Anderson S, Bryant J, et al. N Engl J Med. 2002;347:1233-41. PMID: 12393820.
- Veronesi U, Cascinelli N, Mariani L, et al. N Engl J Med. 2002;347:1227-32. PMID: 12393819.
- Vallasiadou K, Young OE, Dixon JM. Br J Surg. 2003;90:44.
- Azu M, Abrahamse P, Katz SJ, et al. Ann Surg Oncol. 2010;17:558-63. PMID: 19847566.
- Taghian A, Mohiuddin M, Jagsi R, et al. Ann Surg. 2005;241:629-39. PMID: 15798465.
- Morrow M, Harris JR, Schnitt SJ. N Engl J Med. 2012; 367:79-82. PMID: 22762325.
- Singletary SE. Am J Surg. 2002;184:
383-93. PMID: 12433599.
- Houssami N, Macaskill P, Marinovich ML, et al. Eur J Cancer. 2010;46:3219-32. PMID: 20817513.
- Holland R, Veling SH, Mravunac M, et al. Cancer. 1985;56:979-90. PMID: 2990668.
- Morris AD, Morris RD, Wilson JF, et al. Cancer J Sci Am. 1997;3:6-12. PMID: 9072310.
- Anderson SJ, Wapnir I, Dignam JJ, et al. J Clin Oncol. 2009;27:2466-73. PMID: 19349544.
- Fisher B, Dignam J, Bryant J, et al. J Natl Cancer Inst. 1996;88:1529-42. PMID: 8901851.
- Fisher B, Dignam J, Mamounas EP, et al. J Clin Oncol. 1996;14:1982-92. PMID: 8683228.
- Dixon JM. “Breast-conserving surgery: the balance between good cosmesis and local control,” in A Companion to Specialist Surgical Practice: Breast Surgery. Ed. Dixon JM. Edinburgh: Elsevier, 2009.
- Al-Ghazal SK, Blamey RW. Breast. 1999;8:162-8. PMID: 14731434.
More Is Better
Melvin J. Silverstein, MD
Hoag Memorial Hospital Presbyterian; Keck School of Medicine, University of Southern California
In 1999, my colleagues and I published a paper in the New England
Journal of Medicine showing that patients with ductal carcinoma in situ
(DCIS) treated by excision alone had a very low local recurrence rate
(about 5% at 10 years), if clear margins of 10 mm or more were achieved.
1
Following that paper and the presentation of those data at numerous
meetings, word spread that I no longer used radiation therapy (even for
invasive cancer), that I required 10-mm margins for all cases or I
returned to the operating room for re-excision or mastectomy, and that I
voted Republican. None of those were true. But somehow, erroneously, I
became the guru for 10-mm margins without breast irradiation for all
patients with breast cancer, both noninvasive and invasive.
So, let me set the record straight. I always recommend breast
irradiation for patients with invasive cancer receiving
breast-conserving therapy and for about half of my patients with DCIS.
The exception, which follows NCCN guidelines,
2 are patients
with DCIS with small, well-excised, low-grade lesions (low University of
Southern California/Van Nuys Prognostic Index scores).
3-5
Moreover, I routinely accept 1 mm as a clear margin, and I do not
require re-excision, if radiation therapy is going to be used. While I
intuitively prefer wider margins, I’m willing to accept narrow but clear
margins. With that said, can I prove that wider margins are better?
I admit that in 2001, while giving the Keynote Lecture at the American Society of Breast Surgeons Annual Meeting, I did say, “
Margins are like money. More is better.”
I still feel that way, but Mike Dixon is right. I cannot prove that 2
mm is better than 1 mm, nor that 3 mm is better than 2 mm. I cannot
prove an incremental benefit because the precise measurement of margin
width was not common until recently, and the prospective, level I
evidence that would be required to prove an incremental benefit simply
does not exist. Nevertheless, wider margins make sense, and most
surgeons and radiation oncologists would prefer a wider margin, if there
were no cosmetic cost.
For patients with DCIS treated with excision alone (no radiation
therapy), wider margins correlate with less residual disease and a lower
local recurrence rate.
6-8 Those benefits may not be so
apparent for patients with invasive cancer because the value of wider
surgical margins is blunted by both radiation therapy and the addition
of other adjuvant treatments.
I do not want wider margins at significant cosmetic cost. What I do want
is wider margins and better cosmesis. I want both. In support of that,
and dating back to the 1980s and the Van Nuys Breast Center, I have
always been a champion of oncoplastic breast conservation. I have always
trained residents and breast fellows to believe that the appearance of
the breast after breast preservation is important and that it should be
equal or better than before the initial excision, if possible.
Gains from wider excisions
In an attempt to understand what is gained by wider excision, my
colleagues and I recently analyzed 100 consecutive excisions using a
simple ellipse and compared those cases with 100 consecutive excisions
using an oncologically designed reduction mammoplasty, in which a larger
amount of tissue could be removed while achieving a better cosmetic
result.
9 The data are outlined in the Table below:
In this series, when compared with a conventional elliptical excision,
oncoplastic reduction routinely produced larger specimens, wider
margins, a lower percentage of close or transected margins, and a lower
re-excision rate. Oncoplastic reduction achieved all these benefits
while routinely producing better cosmetic results.
When wider margins = better cosmesis
|
 |
| Fig. 1:
Preoperative (L); Two years postoperative (R): A patient with a large
upper central left breast carcinoma treated with neoadjuvant
chemotherapy and wide segmental resection, using a split reduction
excision, followed by radiation therapy. Complete excision with wide
margins as well as excellent cosmesis were achieved. |
Figure 1 shows a woman with a large upper central left breast cancer.
She would have been deformed with a standard excision, or, more likely,
she would have been treated with a mastectomy and her reconstruction
compromised by post-mastectomy radiation therapy. The use of neoadjuvant
chemotherapy followed by an oncoplastic split reduction excision and
radiation therapy yielded widely clear margins and a far superior
cosmetic result (a win-win: wider margins and better cosmesis). Her
long-term survival will be equivalent to standard lumpectomy or
mastectomy, and she will be a far happier patient.
A reduction excision offers additional benefits. When clear margins are
achieved during the first operative procedure, re-excision or conversion
to mastectomy is eliminated, resulting in substantial cost savings and
the elimination of the additional psychic trauma of a second procedure.
The removal of excess breast tissue from the contralateral breast, while
achieving symmetry, also appears to lower the overall risk of a future
contralateral breast cancer.
10,11
I cannot prove to you that wider excision leads to a lower local
recurrence rate when radiation therapy and modern adjuvant treatment is
given, although I believe that it does, in a small fraction of patients;
but it clearly leads to fewer re-excisions and fewer mastectomies.
However, if wider excisions affect your cosmetic results negatively,
then I agree, you should not be doing wider excisions. Perhaps you
should not be doing breast surgery. After all, it is 2013.
Dr. Silverstein is Director of the Hoag Breast Program at Hoag
Memorial Hospital Presbyterian, and Clinical Professor of Surgery at the
Keck School of Medicine, University of Southern California. He has
served on ASCO’s Scientific Program Committee.
References
- Silverstein MJ, Lagios M, Groshen S, et al. New Engl J Med. 1999;340:1455-61. PMID: 10320383.
- Carlson RW, Allred DC, Anderson BO, et al. NCCN Clincal Practice Guidelines in Oncology: Breast Cancer. 2008; nccn.org.
- Silverstein MJ. Am J Surg. 2003;186:337-43. PMID: 14553846.
- Silverstein MJ, Buchanan C. Breast. 2003;12:457-71. PMID: 14659122.
- Silverstein MJ, Lagios M. J Natl Cancer Inst Monogr. 2010;41:193-96. PMID: 20956828.
- Silverstein M. Women’s Health. 2008;4:
565-77. PMID: 19072459.
- Silverstein MJ. “Margin width as the sole predictor of local
recurrence in patients with ductal carcinoma in situ of the breast,” in
Silverstein MJ, Recht A, Lagios M, eds. Ductal Carcinoma in Situ of the Breast. 2nd ed. Philadelphia: Lippincott, Williams and Wilkins; 2002.
- Silverstein MJ, Lagios M, Lewinsky B, et al. Breast Cancer Res Treat. 1997;46:23.
- Kopkash K, Savalia N, Silverstein MJ. A Comparison of Breast
Conservation Methods: Ellipse Verses Reduction Excision. Submitted
American Society of Breast Surgeons Annual Meeting 2013.
- Boice J, Persson I, Brinton L, et al. Plast Reconst Surg. 2000;106:755-62. PMID: 11007385.
- Brinton L, Persson I, Boice J, et al. Cancer. 2001;91:478-83. PMID: 11169929.
The views and opinions expressed in Current Controversies in
Oncology are those of the authors alone. They do not necessarily reflect
the views or positions of the Editor or of the American Society of
Clinical Oncology.
Often patients will arrive with an outside biopsy. The biopsy should be processed for p16 testing and a reflex HPV test if p16+. There are no other molecular markers that are indicated for routine testing yet.
Director, Head and Neck Medical Oncology, Division of Hematology/Medical Oncology, Mount Sinai School of Medicine
Professor of Medicine, and Professor of Gene and Cell Medicine, The Tisch Cancer Institute
New York, NY
While surgery could be accomplished initially, it does not address the biology of this disease, which will require post-operative CRT and possesses a high risk of distant metastases. In addition, the functional consequences of the surgery would significantly reduce this patient's quality of life (NCCN, 2012).1
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