Những Nguyên Tắc Thiết Yếu Trong Phẫu Thuật Tuyến Vú (Essentials of Breast Surgery)

harboring disease and discussion of the inter-
pretation and potential benefits of testing.
Who should be referred to a genetic coun-
selor? Genetic counseling is appropriate for any
patient who believes that she or her family is at
increased risk of developing breast or ovarian
cancer. Not all of these patients do carry an
increased risk, and counseling may help alleviate
fears and stop patients from choosing extensive
surgery that may not be in their best interest.
In addition, patients determined to have an
increased risk of possessing a genetic predisposi-
tion to breast or ovarian cancer, based on a thor-
ough history, should be referred for genetic
counseling (Box 10–3). It is also important not
to overlook syndromes other than BRCA1 or
BRCA2 that may be associated with breast
cancer. Li-Fraumeni syndrome (p53 mutation)
should be suspected in a young woman with
breast cancer who has a personal or family his-
tory that includes soft tissue sarcomas, osteosar-
comas, brain tumors, or leukemias. Histories
that include breast cancer, benign breast disease,
thyroid, renal, and endometrial cancer may sug-
gest Cowden syndrome (PTEN).
Presentation at a
Multidisciplinary Tumor Board
Finally, before proceeding with treatment, it is
prudent to present patient cases at a breast cancer
multidisciplinary tumor board (Box 10–4). The
treatment of breast cancer is multimodal and
increasingly complex. The old scenario in which
the surgeon evaluates the patient, proceeds with
surgery, and then refers the patient to medical
and radiation oncologists is becoming less ap-
propriate as the management of breast cancer
changes. There are several advantages to the
multidisciplinary approach.
One significant advantage is that it allows for
review of the pathology and radiology in a group
setting. This is particularly important if the
patient had x-ray studies or biopsies at anoutside
institution because it allows for a second and
potentially an expert review of the findings. In
many cases, this review may change the recom-
mended surgery. Review of the mammogram
may reveal a second area of suspicion that
requires biopsy before proceeding with lumpec-
tomy or calcifications that preclude breast con-
servation. Review of the pathology may change
the margin status, affecting the need for reexci-
sion, or it may find or question the presence of
an invasive component in predominantly in situ
disease, changing recommendations for axillary
staging. The tumor board setting also facilitates
direct communication between the surgeon,
radiologist, and pathologist in planning surgery.
Given that radiation is a crucial component
of breast conservation therapy, it is prudent
to have the radiation oncologist and the sur-
geon review the history, physical, and imaging
findings together before deciding upon breast
conservation. Concerns of the radiation on-
cologist, based on comorbidities, underlying
medical conditions, body habitus, or mam-
mographic findings, may prevent a scenario
wherein the surgeon feels lumpectomy is
appropriate, only to have the patient return
for a mastectomy after a consultation with a
BOX 10–3 PATIENTS WITH
INVASIVE BREAST CANCER FOR
WHOM GENETIC COUNSELING/
TESTING SHOULD BE CONSIDERED


Diagnosed at a young age (<40)


Patients with bilateral cancers or both
breast and ovarian cancer


Patients with two or more close relatives
with breast or ovarian cancer


Patients with a family member who
developed breast or ovarian cancer
before age 50, had both breast and
ovarian cancer, or bilateral breast cancer


Patients with a male relative who had
breast cancer


A positive BRCA1 or BRCA2 genetic test
in a relative


Ashkenazi (Eastern European) Jewish
ancestry
BOX 10–4 PARTICIPANTS IN A
BREAST CANCER TUMOR BOARD


Genetic counselors


Medical oncologists


Nurse coordinators


Pathologists


Psychologists/psychiatrists


Radiation oncologists


Radiologists


Research nurses


Social workers


Surgeons
141
10—WORKUP AND STAGING OF THE BREAST CANCER PATIENT

radiation oncologist. For patients who require
a mastectomy, the need for postmastectomy
radiation might influence the type and timing
of reconstruction, and in some cases this may
prompt an SLN biopsy before mastectomy to
determine whether immediate reconstruction
is appropriate.
One of the most important angles of the mul-
tidisciplinary tumor board is the dialogue
between the medical oncologist and surgeon
on the use of neoadjuvant chemotherapy. Che-
motherapy before surgery is increasingly used
to downstage operable tumors, and it has other
advantages as well (see Chapter 18). Many
patients may be better served by completing
chemotherapy before surgery, assuming the
patients are deemed appropriate candidates for
chemotherapy. The tumor board setting allows
for a discussion of not only when neoadjuvant
chemotherapy might be appropriate, but also
how to handle regional staging (SLN before or
after chemotherapy), whether BCT would be
appropriate even if the primary tumor is down-
staged, and whether neoadjuvant hormonal
therapy may be preferred to chemotherapy.
Even when neoadjuvant chemotherapy is not
necessary, having medical oncologists review
the case in the beginning can change surgical
management, especially in cases of recurrent
disease.
Beyond the oncologists, surgeons, and radia-
tion oncologists, there are other aspects to the
tumor board setting that are advantageous to
both the clinicians and the patients. Reviewing
the family history with the genetic counselor
present helps determine who should be referred
for genetic counseling and facilitates this pro-
cess. Likewise, the early intervention of social
workers and psychologists may help patients
having a difficult time with their diagnosis or
other obstacles to receiving appropriate care.
Also important is the presence of research
nurses who can help identify patients appropri-
ate for open research protocols.
Patients are often concerned that the time it
takes to get a second opinion from a multidisci-
plinary team may be detrimental. They feel that
the cancer needs to be removed as soon as possi-
ble and any delay may lead to the development
of metastatic disease. Patients should be assured
that they have time to get all the necessary
information and make the right decision with-
out jeopardizing their chance of cure. Another
question is whether all patients need to be
reviewed or if just the “complex cases” should
be. It may not be feasible to present all new
patients in this manner; however, it is often in
the “straightforward” cases that a change in
the radiology or pathology report alters surgical
management. Thus it seems most prudent to
review most cases with the tumor board,
although the reality of this depends upon the
resources available.
Suggested Readings
1. Green FL, Page DL, Fleming ID, Fritz A, eds. AJCC
Cancer Staging Manual, 6th ed. Chicago: American
Joint Committee on Cancer, 2002.
2. National Comprehensive Cancer Network (NCCN)
Clinical Practice Guidelines in Oncology. Available
at
default.asp.
3. Newman EA, Guest AB, Helvie MA, et al. Changes in
surgical management resulting from case review at a
breast cancer multidisciplinary tumor board. Cancer
2006;107(10):2346–2351.
4. Singletary SE, Allred C, Ashley P, et al. Revision of the
American Joint Committee on Cancer staging system
for breast cancer. JCO 2002;20(17):3628–3636.
5. Singletary SE, Connolly JL. Breast cancer staging:
Working with the 6th edition of the AJCC Cancer
Staging Manual. CA Cancer J Clin 2006;56:37–47.
142
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

11
Management of Ductal
Carcinoma In Situ and
Paget Disease
INCIDENCE
NATURAL HISTORY
CLASSIFICATION
PRESENTATION
TREATMENT
Mastectomy
Breast Conservation Therapy
Lumpectomy Alone for DCIS
Management of the Axilla
Hormonal Therapy
PAGET DISEASE
Clinical Presentation
Treatment
Management of Ductal Carcinoma In Situ and Paget
Disease: Key Points
Appreciate the presentation of DCIS and the changes in incidence
since the introduction of screening mammograms.
Understand the natural history of DCIS and the implications for treatment.
Know the advantages and disadvantages of breast conservation therapy versus
mastectomy for patients with DCIS.
Be familiar with the NSABP and EORTC trials of radiation after lumpectomy
for DCIS.
Understand the role of tamoxifen after surgery for DCIS.
Describe the clinical presentation and appearance of Paget disease.
Know the treatment options for patients with Paget disease and the
implications of the mammographic findings.
Ductal carcinoma in situ (DCIS) is a non-
invasive form of ductal carcinoma, limited
to the confines of the basement membrane
of the duct (also referred to as intraductal
carcinoma). It represents an intermediate stage
in the histologic progression of normal breast
tissue to invasive ductal carcinoma. Most inva-
sive ductal carcinomas appear to originate
143

from DCIS, as evidenced by similar genetic
changes in invasive cancers adjacent to in situ
disease, although the exact mechanisms and
pathways
of
tumorigenesis
are
not
well
understood.
Before the era of screening mammography,
DCIS was a relatively uncommon presentation
of breast cancer. Today, however, DCIS makes
up about 15% to 30% of breast cancer cases.
DCIS typically starts in the small to medium-
sized ducts with exaggerated ductal cellular
proliferation and is generally thought to be
a
precursor
to
invasive
ductal
carcinoma.
Although DCIS is stage 0 breast cancer and
thought of as an innocuous lesion, the term
DCIS encompasses a variable group of lesions
with a wide spectrum of histologic and path-
ologic features, diverse malignant potential,
and multiple treatment options. The treat-
ment of DCIS within the breast is extremely
similar to that of invasive ductal carcinoma,
while the concern for regional or distant disease
is much less.
Incidence
The detection of noninvasive breast cancer
increased dramatically with screening mam-
mography. Before this, DCIS was a very differ-
ent disease entity, often presenting as either a
palpable mass, nipple discharge, or Paget dis-
ease (see later). It represented only a small frac-
tion of breast cancer cases (approximately 1%
to 3%). Unsure exactly how to treat it, recom-
mendations ranged from simple observation
to modified radical mastectomy. Between 1983
and 1992, as screening mammography became
widespread, incidence rates increased dramati-
cally. This increase in the incidence of DCIS
has been most pronounced among women
between the ages of 40 and 69.
The incidence of DCIS continues to increase,
with more than 62,000 cases in 2007. Today,
DCIS accounts for more than 20% of all new
cancer diagnoses and approximately 42% of
all mammographically detected malignancies.
How much of the increase is due to increased
screening and how much may be a true
increased incidence of DCIS is unknown. The
risk factors for DCIS and invasive cancer are
identical and include a personal history of
breast cancer, family history, nulliparity, or
older age at first birth.
Although the concept of a localized prein-
vasive form of breast cancer dates back to
1906, the actual term in situ was not coined
until 1932. Basically, DCIS is thought to be
an exaggerated multiplication of cells in the
ductal system with a propensity toward longi-
tudinal rather than radial growth; these cells
remain within the confines of the basement
membranes. A constellation of subtypes have
been recognized, each with their individual
architectural characteristics, invasive poten-
tial, and prognostic significance (Box 11–1).
BOX 11–1 Terms Used to Describe
DCIS


Multifocal DCIS is an entity
wherein multiple, apparently separate
foci of disease occur within the same
quadrant of the breast. Upon closer
evaluation by three-dimensional
reconstructions of the cross-sectional
segments, 99% of these seemingly
disconnected areas are in essence
unifocal, harboring disease arising
from convolutions of the same duct
system.


Multicentric DCIS on the other hand
refers to foci of disease present in
different quadrants of the breast arising
simultaneously in different disconnected
duct systems. On average, 30% of cases
of DCIS are believed to be multicentric.


Microinvasive DCIS has been defined by
the American Joint Committee on Cancer
(AJCC) as the extension of cancer cells
beyond the basement membrane into
adjacent tissues with no focus more than
1 mm in greatest dimension. Lesions
fulfilling this criterion are staged as
T1mic, a subset of T1 breast cancer. It
is important to remember that with
multiple foci of microinvasion, only the
focus with the largest dimension is used
to classify the lesion and the sizes of
individual foci are not added together.


Extensive intraductal component (EIC) is
a term used to describe a particular
morphology of invasive carcinoma with
associated DCIS comprising more than
25% of the tumor volume along with an
additional extra-tumoral focus of DCIS.


Paget disease of the breast is defined
clinically by the finding of eczematous,
scaly skin at the nipple-areolar complex.
It is associated with underlying breast
cancer (invasive and/or in situ) in 97%
of cases. A less common presentation of
breast cancer, it is important to consider
Paget disease in any patient presenting
with a persistent nipple-areolar complex
abnormality.
144
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

Historically DCIS has been classified into
five subtypes (postulated to represent steps in
evolution and worsening malignant potential)
based on architectural pattern: micropapil-
lary, papillary, cribriform, solid, and comedo
(Table 11–1) (Figs. 11–1 through 11–3). More
recently the emphasis has been on the pres-
ence of necrosis and nuclear grade (Fig. 11–4).
This is based on the fact that these factors have
the most significant association with microin-
vasive disease and the propensity for recur-
rence. DCIS is not associated with a high risk
of regional or distant recurrence, so the focus
centers on local control, particularly on pre-
venting an invasive recurrence. This is par-
ticularly true as more women opt for breast
conservation. Hence the current recommenda-
tion is for each histopathologic report to indi-
vidually comment upon morphology, nuclear
TABLE 11–1
Traditional Architectural Classification for DCIS
Architectural
Pattern
Cytologic
Features
Calcifications
Cell
Necrosis
Micropapillary
Intraluminal projection of cells, club shaped, lack
fibrovascular
Minimal, small
Limited to
single cells
Papillary
Intraluminal projection of tumor cells,
fibrovascular cores
Minimal, small
Variable
Cribriform
Small cells, small hypochromatic nuclei, back-to-back
glands
Minimal, small
Limited to
single cells
Solid
Not as well defined, tumor cells fill and distend
involved space
Variable
Not
significant
Comedo
Large cells, nuclear pleomorphism, mitotic activity,
often associated with microinvasion
Linear,
branching
Prominent
Figure 11–1. Micropapillary growth pattern of duc-
tal carcinoma in situ. A proliferation of neoplastic cells
replace the epithelium lining and form small pro-
jections. These can coalesce, forming curvilineous
structures. (Image courtesy of Maria Braman, MD,
Department of Pathology, University of Michigan.)
Figure 11–2. Cribriform growth pattern of ductal
carcinoma in situ. These cells entirely fill the ducts
and the cells form secondary glandular lumina.
(Image courtesy of Maria Braman, MD, Department
of Pathology, University of Michigan.)
Figure 11–3. Solid growth pattern of ductal carci-
noma in situ. The cells completely fill the duct with-
out necrosis. (Image courtesy of Maria Braman, MD,
Department of Pathology, University of Michigan.)
145
11—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE

grade, and necrosis. Several systems exist for
classifying DCIS by these features (Table 11–2).
Natural History
Ductal carcinoma in situ is generally thought
to be a precursor lesion to invasive carcinoma;
a step in the transition from normal cells of
the duct to frankly invasive cancer. It is impor-
tant to keep in mind, however, that the pro-
gression from cellular proliferation, to atypical
hyperplasia, to noninvasive cancer, and ulti-
mately to invasive cancer has been hypothe-
sized yet never proven. Some have suggested
that a good portion of mammographically
detected DCIS is clinically indolent and would
never lead to invasive cancer. If this is the case,
we may be overtreating DCIS, extending sur-
gery and radiation therapy to patients unlikely
to benefit. This argument is supported in part
by autopsy studies showing DCIS occurring in
1% to 18% of women.
Past
studies
of
patients
with
DCIS
left
untreated due to missed diagnoses provide
valuable insights; there is convincing evidence
that most DCIS would proceed to invasive can-
cer. After 30 years of follow-up, approximately
two thirds of these patients progressed to inva-
sive disease. This clearly demonstrates that
most DCIS lesions will evolve into invasive
cancers, yet a significant proportion do not.
The disease-free subset most likely represents
low-grade disease with small residual tumor
burden or even lesions that were incidentally
completely excised upon biopsy. The fact that
the same risk factors exist for DCIS and inva-
sive ductal carcinoma is additional proof.
However, better definition of the molecular
factors required for DCIS to progress to inva-
sive disease is needed to better differentiate
between the cases of DCIS that could in the
future be safely observed versus those cases
that may need treatment.
Studies suggest that DCIS most commonly ori-
ginates from a single site with longitudinal
extension along the ductal systems. Cross-
sectional proliferation and progression to inva-
sion occurs concurrently, so the larger the area
of DCIS, the more likely it is that there are micro-
invasive foci. There is a much higher prevalence
of invasive disease in cases of diffuse DCIS.
By definition, unless microinvasive disease is
present, DCIS does not invade through the base-
ment membrane and therefore cannot spread to
the regional lymph nodes or distally. Review of
modified radical mastectomy specimens per-
formed for DCIS more than two decades ago
shows concurrent axillary disease in only 2% to
3% of patients. Similar proportions were seen
to develop distant metastasis despite adequate
local treatment. This most likely represents
missed foci of microinvasion, although the pos-
sibility of an inherently aggressive form of DCIS
cannot be ruled out.
Classification
Although DCIS has classically been classified
by morphology, for clinical purposes, many
authors have simply characterized DCIS as com-
edo and noncomedo. The cells of comedo DCIS
have a more malignant appearance; this is
reflected biologically because comedo DCIS is
more likely to be associated with invasive can-
cer than noncomedo DCIS. Even this simple
classification system is complicated by the fact
that larger lesions may have more than one
pattern and there is significant interobserver
Figure 11–4. Comedonecrosis. The cells completely
fill the duct, but the central core becomes necrotic.
(Image courtesy of Maria Braman, MD, Department of
Pathology, University of Michigan.)
TABLE 11–2
Histopathologic
Classifications for DCIS
European
Van Nuys
Lagios
Well differentiated
Non–high
grade
No necrosis
Low grade
Moderately
differentiated
Non–high
grade with
necrosis
Intermediate
grade
Poorly
differentiated
High grade
High grade
146
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

variation in labeling DCIS as comedo or nonco-
medo. Two other important pathologic features
are nuclear grade and the presence of necrosis.
Silverstein and colleagues have proposed divid-
ing DCIS into three groups: (1) high-grade,
(2) non–high-grade with comedonecrosis, and
(3) non–high grade without comedonecrosis.
Again, however, it is difficult to find concordance
among pathologists using this system and more
importantly, none have been able to accurately
stratify DCIS by risk of local recurrence or devel-
opment of invasive breast cancer.
Presentation
Although today most patients present with an
abnormality on routine screening mammogram,
approximately 9% of patients still present with
a palpable mass, nipple discharge, or as Paget
disease of the breast (a chronic eczematous, scaly
rash at the nipple-areolar complex) (Fig. 11–5).
Any patient presenting with these findings
should undergo mammographic imaging.
Because more than 90% of DCIS lesions diag-
nosed today are clinically occult, dependence
on imaging modalities has become obligatory.
Mammography has emerged as the primary
imaging tool for the detection and diagnosis of
DCIS. Microcalcifications are the most com-
mon mammographic characteristic of DCIS
and are observed in more than 90% of cases
(Fig. 11–6). Less frequently mammographic
findings may include prominent ducts, mass,
or architectural changes.
There is evidence to suggest correlation
between the histopathologic subtype of DCIS
and features of associated mammographic cal-
cifications. The most characteristic feature of
comedo DCIS is casting-type calcifications—
linear branching patterns depicting alignment
in a ductal distribution. Conversely nonco-
medo DCIS is more often associated with fine
punctuate calcifications, usually presenting as
a cluster or a noncalcific mass. Up to 94% of
comedo DCIS have mammographic calcifica-
tions, 87% of which are linear. On the other
hand, only 53% of noncomedo DCIS had
calcifications. In addition, the mammographic
estimation of lesion size for comedo DCIS was
more accurate than for the other subtypes.
Other available imaging techniques, includ-
ing ultrasonography, magnetic resonance imag-
ing, scintimammography, and computerized
thermography, are relatively insensitive in the
absence of invasion. Sonographic features of
DCIS include a higher proportion of oval- or
lobulated-shaped areas with uniform isoechoic
texture and bilateral edge shadowing. Calcifica-
tions may be detected by a high frequency
probe in up to 60% of lesions, usually the com-
edo subtype. Ultrasound’s sensitivity is esti-
mated as 62% for comedo DCIS versus only
30% for noncomedo lesions. Breast magnetic
resonance imaging (MRI) is the most recent
adjunct to breast imaging. The use of MRI in
evaluating invasive breast cancer is still evol-
ving, and recent data suggest a possible role in
accurately assessing the extent of disease as well
as detecting multicentricity or residual disease
after resection. While estimating the extent of
disease in DCIS is equally as important, the
ability of MRI to do this accurately is still under
investigation, and the role of MRI for DCIS
remains experimental.
An abnormality detected on mammography
obligates histopathologic evaluation. The vari-
ous available options include fine-needle aspi-
ration (FNA), percutaneous core-needle biopsy
under stereotactic, sonographic, or tactile guid-
ance (when palpable), and surgical biopsy with
or without wire localization. The absolute sensi-
tivity of FNA in the diagnosis of DCIS is only in
the range of 51% to 55% with more than 35% of
indeterminate cytology lesions later confirmed
as DCIS. Cytology cannot differentiate in situ
versus invasive cancer and therefore FNA is
inadequate for the diagnosis of DCIS. On the
other hand, stereotactically guided core biopsy
with specimen imaging to confirm retrieval of
microcalcifications has a sensitivity up to 91%
to 94%. Ultrasound-guided biopsy techniques
have similar results. Wire localization of micro-
calcifications with surgical excision is used for
Figure 11–5. Paget disease of the nipple. The nipple
areolar complex is scaly and eczematous. (Image
courtesy of Celina Kleer, MD, Department of Pathol-
ogy, University of Michigan.)
147
11—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE

diagnosis if the aforementioned procedures can-
not be performed due to technical or patient-
related factors, a situation that is becoming
increasingly rare.
It is important to remember that image-guided
core biopsy techniques may understage mal-
ignant microcalcifications. Studies indicate that
approximately 10% to 15% of 14-gauge core
biopsy specimens revealing atypical ductal hy-
perplasia (ADH), a benign condition, get histo-
pathologically upgraded to DCIS, microinvasive
carcinoma, or frankly invasive carcinoma after
complete excision. Similarly, DCIS diagnosed by
core biopsy may get upgraded correspondingly.
This rate of upstaging may be reduced by using
larger 11-gauge or 8-gauge core samples. It is
recommended that ADH diagnosed on core
biopsy be completely excised via wire localiza-
tion excision to rule out any residual DCIS or
invasive cancer.
Treatment
With the evolution of our knowledge of the
disease process and its pattern of behavior, the
treatment options have evolved accordingly.
Today, a variety of treatment options, ranging
from excision alone (lumpectomy or breast-
conserving therapy) to mastectomy, with or
without radiation therapy (XRT), have been
proposed for DCIS. When treating invasive
breast cancer, local control efforts may be tem-
pered by the likelihood of distant recurrences
and overall survival. For noninvasive breast
cancer, there is an extremely low likelihood of
distant disease and the overall survival should
approach 99% to 100%. Therefore the goal of
therapy centers squarely on local control.
Approximately one half of all recurrences will
be invasive, carrying the associated risks of
metastases and decreased survival.
Once DCIS has been established with tissue
biopsy, the treatment is directed at complete
resection of all disease and the prevention of
recurrence. Treatment must be individualized
to each patient to accomplish these goals.
The extent of disease, the size of the lesion,
any prior history of breast cancer and/or XRT,
occult invasive cancer coexisting with the in
situ lesion, and multicentricity are important
factors in determining the best treatment for
disease control. Patients should be counseled
and involved in the decision-making process.
A
B
Figure 11–6. Mediolateral oblique and magnification views demonstrate regionally distributed pleomorphic
calcifications. Pathology demonstrated ductal carcinoma in situ. (Images courtesy of Dr. Alexis Nees, Depart-
ment of Radiology, University of Michigan.)
148
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

Mastectomy
Historically, mastectomy was the treatment of
choice for DCIS, with cure rates approaching
98% to 99%. Reported failure rates after mas-
tectomy are in the range of 1% to 3%, and
almost all of these are invasive carcinomas,
presenting as chest wall, axillary or distant
recurrence. This may be explained by the fact
that high-grade comedo DCIS may contain
areas of invasion or microinvasion that remain
undiagnosed with standard histopathologic
evaluation protocols, or these are new primary
cancers in residual breast tissue.
Although
mastectomy
has
the
lowest
reported failure rate and is considered the
gold standard for the management of DCIS,
it may be more aggressive than is necessary
for most women with DCIS. With the advent
of breast conservation therapy (BCT) options
for invasive cancer, its application was suc-
cessfully extended to DCIS. However, mastec-
tomy is still the treatment of choice in several
specific situations (Box 11–2). Multicentric
DCIS is one indication for mastectomy. Some
patients will have diffuse microcalcifications
throughout the breast on mammography.
This often represents diffuse disease and even
in those cases where these calcifications are
associated with benign disease, they hamper
the ability to detect recurrence on surveil-
lance mammography. When DCIS is not mul-
ticentric but limited to one area within the
breast, the size of this region relative to the
size of the breast is an important consider-
ation for whether mastectomy is indicated.
This is obviously relative and must be indi-
vidually considered for each patient, but a
large area of disease that cannot be excised
with a cosmetically acceptable result should
be a relative indication for mastectomy. Like-
wise, the inability to obtain histologically
negative margins after multiple attempts is
another indication to proceed with mastec-
tomy. Contraindications to radiation, which
plays a significant role in breast conservation,
must be considered. These include women in
the first or second trimester of pregnancy,
women with connective tissue disorders such
as scleroderma who have unusually high
complications from radiation, and women
who have had previous radiation to the area.
Breast Conservation Therapy
During the mid 1980s to 1990s, there were
various authors who reported their experi-
ences with BCT for DCIS, employing lumpec-
tomy as the primary treatment modality with
or without local XRT (Table 11–3). These indi-
cated compelling evidence in favor of BCT.
A strong argument for the use of adjuvant radi-
ation came unintentionally from the National
Surgical Adjuvant Breast and Bowel Project
(NSABP) protocol B-06. Designed to evaluate
invasive breast cancers, the protocol recruited
a small group of women (78 patients) who
were confirmed to have DCIS upon histopath-
ologic reevaluation. Recurrence rates were in
the range of 43% for lumpectomy alone, but
only 9% for the lumpectomy plus XRT arm.
This prompted the NSABP to launch proto-
col B-17, a prospective randomized trial com-
paring
lumpectomy
alone
to
lumpectomy
plus XRT (50 Gy) for the treatment of DCIS.
More than 800 patients were recruited in total
BOX 11–2 INDICATIONS FOR
MASTECTOMY IN DUCTAL
CARCINOMA IN SITU


Multicentric disease


Diffuse microcalcifications on
mammography


Large tumor size with predictably bad
cosmetic outcome


Contraindication to radiation


Pregnancy


Connective tissue disorder
(scleroderma)


Previous radiation therapy


Patient preference
TABLE 11–3
Trials of Lumpectomy
With and Without Radiation for DCIS
NSABP
B-17
EORTC
10853
UK
DCIS
Number of
patients
813
1002
1030
Follow-up (yr)
12
4
4.4
RR Excision
alone
32%
16%
14%
% Invasive
50%
50%
40%
RR Excision þ
XRT
12%
9%
6%
% Invasive
30%
40%
50%
RR, Recurrence rate; XRT, radiation therapy.
149
11—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE

for both arms of the study with a mean follow-
up of 90 months. Local failure rate for the
group treated with lumpectomy alone was
approximately twice that of the lumpectomy
plus XRT group: 26.8% vs. 12.1%, with half
the recurrent tumors being invasive in the for-
mer and one third in the latter. Pathologic
findings from protocol B-17 showed that the
two biggest predictors of ipsilateral recurrence
were comedo necrosis and the presence of
involved specimen margins (Box 11–3).
A similar trial was simultaneously launched
in Europe by the European Organization for
Research and Treatment (EORTC). After a
median follow-up time of 51 months, a recur-
rence rate of 16% was observed in the group
treated with lumpectomy alone, and 50% of
these were invasive cancers. Patients treated
with
lumpectomy
with
subsequent
XRT
revealed a recurrence rate of 9%, of which
40% were invasive cancers.
Although there have been no prospective
randomized trials comparing mastectomy to
BCT in the treatment of DCIS, the large treat-
ment registries have suggested that, while local
recurrence rates may be lower after mastectomy
than after BCT, there is no difference in overall
survival. The reported cause-specific mortality
from DCIS treated with either mastectomy or
lumpectomy plus XRT is similar (in the range
of 1% to 2%). For DCIS, there is little risk of
metastasis, yet the potential of an invasive
recurrence remains. It is imperative that the
basis of all treatment options for DCIS be the
minimization of the potential risk of an inva-
sive recurrence. At the present time, most
patients are candidates for BCT. The initial
attempt should be to widely excise the entire
area with acceptable margins. Careful preopera-
tive planning is paramount, because the initial
operation is the best chance to achieve com-
plete excision and offer good cosmetic results.
As with all breast biopsies, the surgical speci-
men should be accurately oriented and, if
appropriate, imaged to confirm complete exci-
sion of the radiographic abnormality. If the
lesion is seen to abut a specific margin, an addi-
tional adequate surgical margin should be
obtained
in
the
corresponding
quadrant.
Orienting the specimen correctly and inking it
with a six-color system allows the pathologist
to inform the surgeon whether a specific mar-
gin is either involved or close, allowing for a
more directed reexcision. This provides a better
cosmetic outcome compared to having to reex-
cise the entire lumpectomy cavity. Surgical clips
left along all six biopsy cavity boundaries are
instrumental in delineating the site for accurate
planning of adjuvant radiation therapy boost
dose or partial breast irradiation.
Accurate pathologic assessment of margin sta-
tus is imperative. There is no consensus to date
on what comprises the ideal negative margin
for DCIS. Most institutions strive for at least
2 to 3 mm of circumferential disease-free tissue.
Inadequate
margins
necessitate
reexcision,
hence the importance of orienting and labeling
the specimen at the time of lumpectomy to
guide subsequent surgery. Noninvasive cancers
presenting with calcifications require postopera-
tive mammography to ascertain complete exci-
sion. Residual suspicious calcifications require
localization and reexcision even in the presence
of negative margins.
Lumpectomy Alone for DCIS
It is clear that postoperative radiation as a com-
ponent of BCT offers excellent local control.
However, radiation is not without its side
effects and cost. Whole breast irradiation is
time consuming and can cause cardiac or pul-
monary side effects. There is also the risk of sec-
ond malignancies. Given the fact that many
cases of DCIS treated by excision alone do not
recur, it seems likely that there is a subset of
patients who may be treated by lumpectomy
alone. With careful attention to grade, size,
and margin width, there should be a subset of
patients who could consider treatment by
lumpectomy alone. This may be appropriate
treatment for patients with extremely low-risk
mammographically detected DCIS exhibiting
favorable histopathologic features (low grade,
no necrosis) when resected with an adequate
negative margin. Silverstein and colleagues
have proposed that patients who have under-
gone excision with a minimal margin of 1 cm
do
not
benefit
from
radiation
therapy.
BOX 11–3 RADIATION THERAPY
AFTER LUMPECTOMY FOR DUCTAL
CARCINOMA IN SITU


Radiation therapy (XRT) reduces
ipsilateral breast tumor recurrence by
50% to 60%.


XRT reduces ipsilateral invasive breast
tumor recurrence by 50% to 60%.


After XRT, the annual rate of an invasive
recurrence is 0.5% to 1% per year.


XRT does not improve necessarily
survival.
150
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

However, in an attempt to confirm this, a pro-
spective study of patients with grade 1 or 2 DCIS
underwent excision with margins of greater
than 1 cm. There was a 12% local recurrence rate
after 5 years, with 31% of these being invasive,
and the trial needed to be stopped early due to
the high rate of local failure. Other attempts to
confirm that an adequate excision of a low-grade
lesion may not require radiation have been ham-
pered by the fact that the definition of “adequate
margins of excision” varies amongst institutions
and has not been clearly defined. Ongoing pro-
spective studies in both Europe and the United
States are attempting to answer these questions.
To date, though, no subgroup has been identi-
fied that does not benefit from radiation therapy.
Until then, for most patients qualifying for BCT,
lumpectomy plus postsurgical XRT is the treat-
ment of choice to minimize the risk of local
recurrence, although the relative risks and bene-
fits of radiation vary and should be discussed in
detail with the patient.
Management of the Axilla (Box 11–4)
Because DCIS is noninvasive, theoretically
there should be no possibility of finding disease
within the regional lymph nodes. However,
studies of modified radical mastectomy for the
treatment of DCIS revealed axillary metastases
in approximately 2% of cases. When patients
with DCIS are found to have disease in the
lymph nodes, the assumption is that there are
possible foci of invasive disease somewhere in
the breast that may have eluded discovery on
pathologic tissue examination. This low risk
of finding disease, however, prompted most
surgeons to abandon the routine practice of
performing a level I and II axillary lymph node
dissection (ALND) in patients being treated
for DCIS. Some surgeons, because of the possi-
bility of invasive disease being present when
there was diffuse DCIS throughout the breast,
continued to advocate a level I ALND when a
mastectomy was performed.
When
lymphatic
mapping
and
sentinel
lymph node (SLN) biopsy became routine in
the
management
of
breast
cancer,
this
prompted a rethinking of whether the regional
nodes should be looked at when treating DCIS.
Because the pathologist may serial-section just
one or two nodes, rather than bisecting 10 to
30 nodes as with an ALND specimen, SLN
biopsy is more sensitive for finding microme-
tastatic disease. When SLN biopsy is used in
DCIS, the results have shown wide variability,
with some series describing 3% to 10% of
patients with DCIS having a positive sentinel
lymph node (SLN). This has prompted a hand-
ful of surgeons to recommend the routine use
of SLN biopsy for DCIS; however, most sur-
geons question the prognostic significance of
these findings. Most of the disease detected
was
found
by
immunohistochemistry,
for
which we do not know the prognostic implica-
tions. In addition, it is hard to reconcile long-
term survivals of 99% for pure DCIS with a
nodal positivity rate of 5% to 10%.
Therefore neither lymph node dissection
nor
lymphatic
mapping
and
SLN
biopsy
should play a role in the routine management
of pure DCIS, with two notable exceptions.
The first is when there is a high likelihood of
finding invasive disease. These would include
cases in which the DCIS presents as a mass or
there is a high suspicion of invasion on either
the imaging studies or the biopsy specimen.
In these cases it is reasonable to perform a sen-
tinel node biopsy in conjunction with lumpec-
tomy, although for patients being treated by
BCT, axillary staging can just as reasonably be
deferred until the diagnosis of invasion is con-
firmed. Any patients with documented micro-
invasion should have axillary evaluation by
SLN biopsy. The second indication for lym-
phatic mapping in the management of DCIS
is in the patient undergoing mastectomy for
diffuse DCIS, particularly if it is high grade.
In this case, if microinvasive disease is discov-
ered on pathologic examination, it is not pos-
sible to then stage the patient by SLN biopsy
and an ALND might be necessary. Immuno-
histochemistry should not be routinely per-
formed for these cases.
Occasionally, patients undergo a mastec-
tomy with SLN biopsy for DCIS and have met-
astatic disease identified in the sentinel node
but no invasive disease identified in the breast.
The first step should be to perform a more ex-
tensive pathologic examination of the breast
BOX 11–4 INDICATIONS FOR
SENTINEL LYMPH NODE BIOPSY IN
DUCTAL CARCINOMA IN SITU


Patients with microinvasion


Patients undergoing mastectomy for
diffuse disease


Patients with a high suspicion of
harboring invasive disease


Extensive high-grade disease or
necrosis on core biopsy


Imaging studies suggesting invasion
151
11—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE

for invasive disease that may have been over-
looked. This may be facilitated by obtaining
x-rays of the specimen so that more detailed
examination can be performed on areas with
suspicious calcifications. However, even if it
cannot be identified, if there are true metas-
tases in the sentinel nodes, it must be assumed
that the patient does have an undetected focus
of invasion and the patient should be consid-
ered
for
completion
ALND
and
systemic
therapy.
Hormonal Therapy
Because systemic metastases are not a concern
with in situ disease, there is no role for cytotoxic
chemotherapy in the treatment of DCIS. DCIS
does, however, express the estrogen receptor
(ER), although not universally, prompting the
investigation of tamoxifen as an adjuvant to
surgical therapy. The NSABP B-24 protocol stud-
ied the use of tamoxifen in women with DCIS
undergoing BCT. More than 1800 women with
DCIS were randomized to 5 years of tamoxifen
versus placebo. At a median follow-up of 74
months, there was an overall risk reduction of
37% for patients receiving tamoxifen, regard-
less of resection margin, tumor size, or grade.
There was also a decreased risk of contralateral
invasive
and
noninvasive
cancer
by
52%
(Table 11–4). On the other hand, a trial from
the United Kingdom, Australia, and New Zeal-
and failed to demonstrate a significant benefit
to tamoxifen in preventing either ipsilateral or
contralateral events. The UK/ANZ trial was a
smaller study, with a design that allowed for
some patient choice, so the results must be
interpreted with care.
These
results
suggest
that
a
selective
approach must be used when deciding which
women with DCIS should receive adjuvant
tamoxifen. The potential benefits of tamoxifen
both on reducing recurrence and second breast
malignancies must be weighed against the
potential side effects, including venous throm-
boembolism and uterine cancer. The baseline
risk of recurrence, the age of the patient, and
the
relative
risk
of
side
effects
must
be
considered.
In addition, the ER status should be consid-
ered. As stated, ER expression is not 100%
among DCIS patients. In a study derived from
the
NSABP-B24
drug
arm
comparing
the
response of ER-positive versus ER-negative
patients to tamoxifen, recurrence rates were
10% for the ER-positive group compared to
23% for the ER-negative group. Therefore
many institutions have begun routinely evalu-
ating DCIS for ER status by immunohisto-
chemistry and limiting the use of tamoxifen
for patients with ER-positive DCIS.
Recently, the aromatase inhibitor anastra-
zole has received growing attention. Results
of the ATAC (Anastrazole and Tamoxifen:
Alone or in Combination) trial, which rando-
mized 9000 patients with early-stage breast
cancer to receive anastrozole versus tamoxifen
versus the combination, revealed a statistically
significant risk reduction of new breast cancers
in the anastrozole arm (P ¼ .007). However,
there are no data on the use of aromatase inhi-
bitors in patients with DCIS. There are pres-
ently two trials ongoing to address this issue
(NSABP B-35 in the United States and IBIS-II
in Great Britain).
Paget Disease
In 1874, Sir James Paget described 15 women
with chronic nipple ulceration who ultimately
developed cancer of the involved breast within
2 years. He described an eruption on the nip-
ple and areola, similar to acute eczema, with
a copious clear yellowish exudation. Ulti-
mately this would be known as Paget disease
of the breast and is defined clinically as a scal-
ing eczematous lesion of the nipple-areolar
complex.
Paget
believed
that
the
nipple
changes were themselves benign, but later it
was discovered that the cells of Paget disease
were malignant and that Paget disease was
TABLE 11–4
Results of NSABP Protocol B24: Tamoxifen versus Placebo after
Lumpectomy Plus Radiation Therapy
Study Arms
Patients
Local Recurrence
Invasive Recurrence
Survival
Lumpectomy þ
XRT þ placebo
902
87 (9.6%)
40/87 (46%)
97%
Lumpectomy þ
XRT þ tamoxifen
902
63 (7%)
23/63 (37%)
97%
XRT, Radiation therapy.
152
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

carcinoma arising from an intraductal carci-
noma in the subareolar ducts.
Paget disease is associated with either in situ
or invasive cancer in almost all cases. Paget
disease is considerably less common than other
presentations of breast cancer, accounting for
only 1% to 3% of breast cancer cases diagnosed
each year in the United States. Paget disease also
can occur in men, although given the low inci-
dence of male breast cancer overall, this is
extremely rare. Paget disease must be a strong
consideration in the differential diagnosis of
any persistent nipple abnormality in either
men or women.
Although the clinical definition of Paget dis-
ease is relatively straightforward, there is con-
troversy as to its pathogenesis (Table 11–5).
Two main theories have been put forward to
explain the presence of Paget disease. The
more commonly accepted theory is the epider-
motropic theory, which suggests that the cells
migrate from an underlying breast malignancy
into the epidermis of the nipple. The second is
the transformation theory, which suggests that
Paget disease arises from malignant transfor-
mation of the cells within the epithelium of
the nipple itself. Although there may be differ-
ent underlying mechanisms, most evidence
points to the epidermotropic theory.
Clinical Presentation
As stated, the hallmark of Paget disease is a scaly,
raw, ulcerated lesion on the nipple and/or areola.
Usually this starts with the nipple and then
spreads to the areola. There may be ulceration
ordischarge (usually serous but possibly bloody).
Associated
nipple
retraction
suggests
more
advanced disease. The disease is almost always
unilateral, although bilateral cases have been
described (Box 11–5). All patients with nipple
complaints should have a complete breast exam
and bilateral mammography.
The lesion is typically present for several
months before being accurately diagnosed. At
first patients may have pain, burning, or pruri-
tus without any obvious lesion. Patients with
these symptoms should be followed, and fur-
ther investigation initiated if the symptoms do
not resolve. Many times the lesion is thought
to be a benign dermatologic condition and is
treated topically. Often the inflammatory com-
ponent resolves, suggesting improvement. In
some cases, these lesions may improve spon-
taneously. It is important not to completely
rule out Paget disease even if there was some
improvement with or without therapy. The dif-
ferential diagnosis (Box 11–6) includes both
TABLE 11–5
Theories of Pathogenesis of Paget Disease
Theory
Idea
Support
Epidermotropic
Neoplastic cells migrate from underlying
malignancy to the epidermis of the nipple-
areolar complex (NAC).
Paget is almost always associated with
underlying ductal carcinoma.
Immunohistochemical staining of Paget is
usually identical to the underlying cancer.
Molecular markers are also usually
concordant.
Transformation
Epidermal keratinocytes in the nipple
transform into Paget cells and then spread
to the breast.
Not all cases of Paget have underlying
parenchymal cancer.
Tumors may be distal from the NAC.
The “Toker cell” with an appearance between
a keratinocyte and Paget cell is thought to
be a precursor to Paget.
BOX 11–5 ASSOCIATED BREAST
ABNORMALITIES IN PAGET
DISEASE


Palpable breast mass—50%


Mammographic abnormality with no
palpable mass—20%


No underlying mass or mammographic
abnormality—30%
BOX 11–6 DIFFERENTIAL
DIAGNOSIS OF PAGET DISEASE
Benign
Eczema
Erosive dermatitis
Pemphigus vulgaris
Syphilitic lesion
Herpes zoster
Malignant
Bowen’s disease
Basal cell carcinoma
Malignant melanoma
153
11—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE

benign (eczema, dermatitis)and malignant etiol-
ogies (Bowen’s disease, basal cell carcinoma).
If benign disease is suspected, a short course
of topical steroids is reasonable. If the lesion
improves but fails to completely resolve, Paget
should be considered. The next step in the
workup should be biopsy. The diagnosis can
be made by punch or wedge biopsy of the nip-
ple. Shave biopsy or scrape cytology can be
diagnostic, but a negative finding does not
rule out Paget disease. In addition, core-needle
biopsy of any mass or mammographic abnor-
mality should be performed.
The pathologic hallmark of Paget disease is the
presence of malignant, intraepithelial Paget
cells, either singly or in small groups, within
the epidermis of the nipple (Fig. 11–7). They
are large in size with pale cytoplasm and have
high-grade nuclei with prominent nucleoli.
Retraction from the surrounding keratinocytes
can give the appearance of a vacuole. Occasion-
ally these cells can incorporate melanin, making
them difficult to differentiate from melanoma. It
is also sometimes difficult to differentiate Paget
disease from squamous carcinoma of the epi-
dermis (Bowen’s disease) on routine histology.
Immunohistochemical
staining
can
usually
make the diagnosis.
Treatment
Until recently, the standard treatment of Paget
disease has been a simple mastectomy. More
recent data suggest that BCT is feasible, but the
nipple-areolar complex needs to be removed.
A thorough workup with particular attention
paid to any associated palpable mass or mam-
mographic abnormality is crucial to selecting
the proper patients for BCT (Fig. 11–8).
Paget Disease with Palpable Mass
or Mammographic Abnormality
When Paget disease is associated with a palpa-
ble mass, it is more frequently associated with
invasive disease, axillary metastases, and mul-
tifocal
underlying
disease.
Most
of
these
patients will require mastectomy. However, if
it is feasible to perform a lumpectomy that
incorporates both the nipple-areolar complex
and the palpable mass with adequate margins,
and if this would result in acceptable cosmetic
results after whole breast irradiation, then BCT
is reasonable. The same can be said for a focal
nonpalpable mammographic abnormality that
can be resected in continuity with the nipple-
areolar complex.
Many times the palpable mass or mammo-
graphic abnormality is a considerable distance
from the nipple, and even when it is close,
resection of both results in a poor cosmetic
result. These patients may be better served by
simple mastectomy with breast reconstruc-
tion. Patients with large breasts may allow for
adequate resection while still allowing for
acceptable breast contour and symmetry, often
with contralateral breast reduction and nipple
reconstruction. If the patient has a proven
invasive component and clinically negative
nodes, sentinel lymph node biopsy should be
performed at the time of lumpectomy or
mastectomy.
Patients with multicentric lesions or diffuse
microcalcifications should be treated by sim-
ple mastectomy. Sentinel lymph node biopsy
for staging the axilla is recommended in this
situation because of the possibility of discover-
ing invasive disease within the mastectomy
specimen.
Paget Disease with No Mass
or Mammographic Findings
Approximately one third of patients with
Paget disease will not have an associated mass
or
mammographic
abnormality,
but
the
majority of these women will have an underly-
ing carcinoma. Simple mastectomy (with or
without reconstruction) has been the standard
of care, but breast conservation is very reason-
able. Breast conservation consists of resection
of the nipple-areolar complex followed by
whole breast irradiation. Although there are
Figure 11–7. Pathology of Paget disease. The Paget
cells are seen within the keratinizing epithelium of
the nipple epidermis. The Paget cells are large, round
cells with pale cytoplasm and pleomorphic nuclei.
(Image courtesy of Maria Braman, MD, Department
of Pathology, University of Michigan.)
154
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

small series describing excision alone without
radiation,
local
recurrence
rates
are
con-
cerning. Likewise, radiation alone has been
described (after only tissue biopsy) but this
approach has also been associated with high
local recurrence rates.
The idea of excision and radiation for Paget
disease is obviously based on the success of
BCT for both invasive cancer and DCIS. Breast
conservation should consist of complete nip-
ple-areolar resection, because partial resection
may lead to higher local recurrence rates. The
largest series of BCT for Paget disease comes
from a prospective study by the EORTC. After
nipple-areolar resection with negative margins
followed by whole breast irradiation, the local
recurrence rate was only 6.5% after a median
follow-up of 6.4 years.
Negative margins are mandatory, and posi-
tive or close margins (<3 mm) should prompt
reexcision. SLN biopsy is not essential at the
time of nipple-areolar resection, because in
the absence of a palpable mass, the underlying
malignancy is typically intraductal and axil-
lary node involvement is rare. However, it is
not an unreasonable option. After completion
of therapy, there are several techniques that
can be used to reconstruct the nipple-areolar
complex with excellent cosmetic outcomes.
After surgery and radiation, patients should
Negative margins
attainable?
Consider tamoxifen for
contralateral prophylaxis
Radiation;
consider tamoxifen to
prevent recurrence and
for contralateral
prophylaxis
Biopsy of abnormal lesion
if BCT is considered
Lesion and NAC can be
excised with negative
margins?
Lumpectomy
including NAC.
SLN as indicated
Simple mastectomy
SLN biopsy
Yes
No
Yes
No
Patient interested in breast
conservation?
Resection of NAC
Simple mastectomy
Consider SLN biopsy
Consider tamoxifen for
contralateral prophylaxis
Radiation;
consider tamoxifen to
prevent recurrence and
for contralateral
prophylaxis
Patient presenting with
Paget disease
Mass or MGM finding
Full history and physical,
bilateral mammogram, possible MRI
No mass or MGM finding
Negative margins
attainable?
Yes
Yes
No
No
Figure 11–8. Management of Paget disease. In addition to a biopsy of the Paget to confirm the diagnosis, the
workup should include a breast examination, bilateral mammogram, and possibly MRI to identify an associated
mass or abnormality. Biopsy of this mass may help in planning treatment if breast conservation therapy (BCT)
is a consideration. If the nipple-areolar complex (NAC) and any associated lesion can be resected with negative
margins, a lumpectomy is an option, with subsequent radiation and possible NAC reconstruction in the future.
If not, a simple mastectomy is indicated. Sentinel lymph node biopsy at the time of mastectomy is reasonable
given the possibility of an unrecognized invasive component. The benefits of hormonal therapy can be extra-
polated from the ductal carcinoma in situ data.
155
11—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE

be considered for adjuvant hormonal therapy.
Although there is no specific evidence sup-
porting the use of tamoxifen or Arimidex after
BCT for Paget disease, data can be extrapolated
from the DCIS literature. Tamoxifen can also
be considered after mastectomy for prophy-
laxis of the contralateral breast.
Suggested Readings
1. Bijker N, Rutgers EJ, Duchateau L, et al. Breast-
conserving therapy for Paget disease of the nipple.
A prospective European Organization for Research
and Treatment of Cancer study of 61 patients.
Cancer 2001:91:472.
2. Dupont W, Parl F, Hartmann W, et al. Breast cancer
risk associated with proliferative breast disease and
atypical hyperplasia. Cancer 1993;71:1258.
3. Fisher B, Dignam J, Wolmark N, et al. Lumpectomy
and radiation therapy for the treatment of intra-
ductal breast cancer: Findings from the National
Surgical Adjuvant Breast and Bowel Project B-17.
J Clin Oncol 1998;16:441–452.
4. Fisher B, Dignam J, Wolmark N, et al. National Sur-
gical Adjuvant Breast and Bowel Project B24 rando-
mized controlled trial. Lancet 1999;353:1993.
5. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in
treatment of intraductal breast cancer: National Surgi-
cal Adjuvant Breast and Bowel Project B-24 rando-
mised controlled trial. Lancet 1999;353:1993–2000.
6. Fisher ER, Contantino J, Fisher B, et al. Pathological
findings from the National Surgical Adjuvant Breast
and Bowel Project Protocol B-17. Cancer 1995;
75:1310.
7. Hutter RVP. The management of patients with lob-
ular carcinoma in situ of the breast. Cancer 1984;
53:798.
8. Irvine T, Fentiman IS. Biology and treatment of
ductal carcinoma in situ. Exp Rev Anticancer Ther
2007;7(2):135–145.
9. Julien, J-P, Bijker N, Fentiman IS, et al. Radiotherapy
in breast-conserving treatment for ductal carcinoma
in situ: first results of the EORTC randomized phase
III trial 10853. EORTC Breast Cancer Cooperative
Group and EORTC Radiotherapy Group. Lancet
2000;355;528–533.
10. Kawase K, Dimaio DJ, Tucker SL, et al. Paget’s disease
of the breast: There is a role for breast-conserving
therapy. Ann Surg Oncol 2005;12:391–397.
11. Kollmorgen DR, Varanasi, JS, Edge SB, Carson WE
3rd. Paget’s disease of the breast: A 33-year experi-
ence. J Am Coll Surg 1998;187:171.
12. Lagios MD, Margolin FR, Westdahl PR, et al. Mam-
mographically detected ductal carcinoma in situ.
Cancer 1989;63:618.
13. Marcus E. The management of Paget’s disease of the
breast. Curr Treat Options Oncol 2004;5:153–160.
14. Marshall JK, Griffith KA, Haffty BG, et al. Conser-
vative management of Paget disease of the breast
with radiotherapy: 10- and 15-year results. Cancer
2003;97:2142.
15. Mizra NQ, Vlastos G, Meric F, et al. Ductal carci-
noma in situ: Long term results of breast conserv-
ing therapy. Ann Surg Oncol 2000;7:656.
16. Morrow M, Schnitt SJ. Treatment selection in duc-
tal carcinoma in situ. JAMA 2000;283(4):453–455.
17. Orel SG, Mendonca MH, Reynolds C, et al. MR
imaging of ductal carcinoma in situ. Radiology
1997;202:413.
18. Page DL, Dupont WD, Rogers LW, et al. Continued
local recurrence of carcinoma 15-25 years after a
diagnosis of low grade ductal carcinoma in situ of
the breast treated only by biopsy. Cancer 1995;
76:1197.
19. Romero L, Klein L, Ye W, et al. Outcome after inva-
sive recurrence in patients with ductal carcinoma in
situ of the breast. Am J Surg 2004;188:371.
20. Silverstein MJ, et al. A prognostic index for ductal
carcinoma in situ of the breast. Cancer 1996;
77:2267–2274.
21. Solin LJ, Kurtz J, Fourquet A, et al. Fifteen year
results of breast-conserving surgery and definitive
breast irradiation for the treatment of ductal carci-
noma in situ of the breast. J Clin Oncol 1996;
14:754.
22. UK Coordinating Committee on Cancer Research
(UKCCCR). Radiotherapy and tamoxifen in women
with completely excised ductal carcinoma in situ of
the breast in the UK, Australia and New Zealand:
Randomized
controlled
trial.
Lancet
2003;362
(9378):95–102.
23. Winchester DP, Jeske JM, Goldschmidt RA. The
diagnosis and management of ductal carcinoma
in-situ of the breast. CA J Clin 2000;50:184–200.
156
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

12
Surgical Management
of Primary Breast Cancer
CHANGES IN SURGICAL
MANAGEMENT OF BREAST
CANCER
BREAST CONSERVING THERAPY
Patient Selection
Absolute Contraindications
Relative Contraindications
Not Contraindications
OPERATIVE MANAGEMENT OF
BREAST CANCER
Lumpectomy
Reexcision Lumpectomy
Simple Mastectomy
Modified Radical Mastectomy
COMPLICATIONS OF BREAST
SURGERY
Wound Infections
Seroma
Hematoma/Bleeding
Chronic Pain
Chronic Breast Lymphedema/
Cellulitis
Surgical Management of Primary Invasive Breast
Cancer: Key Points
Understand the evolution of the surgical management of breast
cancer.
Know the absolute and relative contraindications to breast conserving surgery.
Develop an algorithm for selecting the appropriate patients for breast
conserving therapy.
Describe the surgical techniques for a lumpectomy, a wire-localized
lumpectomy, and a simple or modified radical mastectomy.
Be familiar with the complications of breast surgery and their management.
Changes in Surgical
Management of Breast Cancer
Going back to the late 1800s, the treatment of
breast cancer was characterized by either wide
excision or simple mastectomy. These resulted
in extremely high rates of local recurrence and
poor survival (Table 12–1). In 1894, William
Halsted proposed that breast cancer was a
local
disease
that
spread
by
contiguous
157

extension, and that more extensive resection
would provide a better chance of disease control
(Halsted’s Theory). That year, he had performed
50 “complete” mastectomies and reported his
experience. Halsted’s radical mastectomy con-
sisted of en bloc removal of the breast, the over-
lying skin, both the pectoralis major and minor
muscles, and the entire axillary contents (level
I, II, and III nodes) (Fig. 12–1).
The radical mastectomy resulted in a signifi-
cant drop in local recurrence rates, and it
quickly became the standard of care for the
treatment of breast cancer. However, despite
the improvement in local control, the curative
potential of this operation remained limited.
In one series of more than 1400 women over a
course of 30 years, only 13% remained free of
disease, and nearly 60% died of breast cancer.
At first this was believed to be because the
mastectomy was not extensive enough, and
so the extended radical mastectomy, which
included resection of the internal mammary
nodes (IMNs) and/or supraclavicular nodes,
was
proposed.
The
Dahl-Iversen
extended
mastectomy included dissection of both the
IMN and supraclavicular nodes with the radical
mastectomy. An even more radical mastectomy
was
the
“super-radical”
mastectomy
that
included four parts (Box 12–1). However, these
failed to improve survival. In a randomized
comparison of the Dahl-Iversen extended radi-
cal mastectomy to simple mastectomy with
radiation to the regional lymph nodes, with ap-
proximately 330 patients per arm, there was no
difference in disease-free or overall survival. In
a European randomized trial between radical
mastectomy and extended radical mastectomy
(including IMNs), there was again no improve-
ment in survival. A much smaller randomized
trial from the University of Chicago also
showed no improvement to removing the
IMNs.
TABLE 12–1
Local Recurrences after Mastectomy
Hasted WS. The results of operations for the cure of cancer for the breast performed at the Johns Hopkins Hospital
from June 1889 to January 1894. The Johns Hopkins Hospital Reports 1894-1895;4:297-350.
A
B
Figure 12–1. The Halsted radical mastectomy involved removing the breast with the overlying skin, the pec-
toralis major and minor muscles, and the level I, II, and III axillary lymph nodes. (From Bland KI, Copeland EM III.
The Breast, 3rd ed. Philadelphia: WB Saunders, 2004.)
158
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

Disappointed by the failure of radical mastec-
tomy to cure women with breast cancer despite
significant morbidity, many surgeons proposed
that a less extensive operation, the modified
radical mastectomy (MRM), could be performed
without compromising
survival.
The
MRM
involves complete removal of the breast tissue
and the underlying fascia of the pectoralis major
muscle, and removal of some but not all of the
axillary lymph nodes (levels I and II). The over-
lying skin and underlying pectoralis muscles
are not removed. Several prospective rando-
mized trials documented equivalent survival
rates with MRM as compared to radical mastec-
tomy, with less morbidity. As a result of these
data, the radical mastectomy has become an
historical footnote in the treatment of breast
cancer, and there are no absolute indications
for radical as opposed to modified radical mas-
tectomy in women with invasive breast cancer.
The fact that less radical surgery did not affect
survival
made
people
question
whether
Halsted’s theory was correct; that breast cancer
was not a local disease that spread contigu-
ously,
but
instead,
systemic
disease
was
ultimately the main determinant of survival.
The question arose as to whether the breast
needed to be removed or could be preserved
without compromising survival. There had
been several reports of breast cancer being treat-
ed by radiation alone (see Chapter 15), and
there was evidence that radiation could elimi-
nate subclinical foci of disease. This allowed
for the combination of limited surgery and radi-
ation therapy as a method of adequately treat-
ing breast cancer while avoiding mastectomy.
Although initially controversial, breast con-
serving therapy (BCT) has become a standard
of care in the management of breast cancer.
BCT refers to the surgical removal of the tumor
(lumpectomy, wide excision, quadrantectomy)
followed by moderate-dose radiation therapy
to eradicate any residual disease. This chapter
focuses on the surgical aspects of BCT and
mastectomy. Chapter 15 focuses on radiation
therapy.
Breast Conserving Therapy
The goals of BCT are to provide the survival
equivalent of mastectomy, a cosmetically accept-
able breast, and a low rate of recurrence in the
treated breast. Although there was great resis-
tance when it was first introduced, six rando-
mized trials involving more than 4000 patients
over 3 decades established that BCT was as effec-
tive as mastectomy for suitable patients with
breast cancer (Table 12–2). It is difficult to com-
pare one trial to another because they were quite
different in design. Some required lumpectomy,
whereas others required the more extensive
quadrantectomy. Some required that the final
margins be negative, whereas others allowed
for positive resection margins. In the European
Organization for Research and Treatment trial,
surgical margins were microscopically positive
in nearly half the patients. The size of the tumors
included were also quite variable. Despite these
BOX 12–1 THE “SUPER RADICAL”
MASTECTOMY


Breast and axillary contents


Internal mammary artery and vein with
internal mammary lymph node chain


Upper mediastinal nodes


Low supraclavicular nodes
TABLE 12–2
Prospective, Randomized Trials of BCT vs. Mastectomy
Trial
Patients
Max
Tumor
Size
Median
Follow-up
Overall
Survival
Local
Recurrence
BCT
Mastectomy
BCT
Mast.
NSABP B-06
1851
4
20
47%
47%
14.3%
10.2%
Milan I
701
2
20
58.3%
58.8%
8.8%
2.3%
NCI
237
5
18.4
54%
58%
22%
0%
EORTC
868
5
13.4
65%
66%
20%
12%
Institut Gustav
Roussy
179
2
10
78%
79%
4%
NR
Danish
905
5
9.8
79%
82%
NR
NR
159
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

differences, none of the six trials demonstrated a
difference in overall survival for BCT compared
with mastectomy. The trials also demonstrated
several points worth mentioning.
When discussing treatment options with
patients, many lean toward mastectomy to avoid
any chance of local recurrence. It is important
to note that mastectomy does not guaran-
tee freedom from local recurrence. This is true
for all stages of breast cancer. Recurrence rates
after mastectomy range from 3% to 20%, dep-
ending on the size of the tumor, the presence of
regional metastases, and the use of systemic the-
rapy. Overall the riskof a local recurrence is about
the same for BCT and mastectomy. Chest wall
recurrences after mastectomy tend to occur later
than in-breast recurrences after breast conser-
vation, although most will occur within the first
3 years after surgery for both groups.
Radiation
eradicates
microscopic
residual
foci that are present in the breast after surgery.
The effects of radiation have no effect on the
future risk of breast cancer. Therefore the risk
of a second primary cancer in the treated
breast is the same as in the contralateral breast.
The six randomized trials all demonstrated
that even when local recurrence was higher (as
with lumpectomy without radiation), overall
survival was the same. This has been interpreted
as meaning that local therapy has minimal if
any effect on the risk of developing distant dis-
ease. Based on this interpretation, surgeons have
been increasingly willing to accept therapies
that have higher rates of local recurrence, argu-
ing that even if an increased number of those
patients ultimately require completion mastec-
tomy, overall survival would not be affected.
But these trials were all individually too small
to detect a small impact on overall survival.
Even if there was no difference in overall
survival when comparing BCT to mastectomy,
patients who had BCT and developed a local
recurrence do have a worse outcome. In one
matched-pair analysis, BCT patients who had
a local recurrence had an overall survival of
71% compared to 81% for those who did not
have a local recurrence. This in itself did not
prove that prospectively preventing a local
recurrence would have improved survival by
this degree. It could be that the local recur-
rence is a marker reflecting the propensity of
the tumor to metastasize distantly. So rather
than metastases developing from the recur-
rence,
the
patients
with
more
aggressive
tumors are more likely to develop both.
So does the prevention of a local recurrence
improve overall survival? Yes, as demonstrated
by the Early Breast Cancer Trialists Collabora-
tive Group (ECGTCG) metaanalysis. Several of
the randomized trials that established the effi-
cacy of breast conservation included arms in
which women underwent lumpectomy alone,
without radiation, and most demonstrated that
despite a significant increase in local recur-
rence, there was no impact on overall survival.
However, these trials did not have the power
to detect a small survival advantage from the
improved local control provided by radiation
therapy. In addition, the morbidity and mor-
tality associated with radiation therapy nega-
ted some survival advantage, particularly with
older methods for delivering radiation. The
most recent update of the ECGTCG metaanaly-
sis demonstrates that the 15-year breast cancer
mortality risks were significantly lower in the
patients who received radiation therapy (30.5
versus 35.9, P ¼ .002). A pooled analysis of
mortality data from 13 randomized trials also
showed a worse survival in women who did
not receive radiation therapy, with an 8.6%
excess mortality. These data clearly demon-
strate that improved local control does impact
survival, and women with an exceedingly high
risk of in-breast recurrence with BCT com-
pared to mastectomy may be better served by
the latter. It also establishes that radiation is
a critical component of BCT.
Patient Selection
Although the surgeon plays many roles in the
management of breast cancer, one of the most
important is deciding whether the patient
is a good candidate for BCT or whether the
patient will require a mastectomy (Box 12–2).
BOX 12–2 WORKUP TO DETERMINE
SUITABILITY FOR BREAST
CONSERVATION


Complete history and physical


Past medical history


Medications


Complete family history


Thorough bilateral breast
examination


Bilateral mammogram with diagnostic
imaging of the cancer


Review of the histology


? Ultrasound of the primary tumor


? Magnetic resonance imaging
160
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

There are several absolute contraindications to
breast conserving therapy, some relative con-
traindications, and some factors that are not
contraindications, but are wrongly thought
to be. The American College of Surgeons, the
American College of Radiology, the College of
American Pathologists, the Society of Surgical
Oncology and the Canadian Steering Commit-
tee on Clinical Practice Guidelines for the Care
and Treatment of Breast Cancer have devel-
oped consensus standards of care for BCT.
The evaluation of the breast cancer patient to
determine whether she is a suitable candidate
for BCT includes:

A complete history and physical examina-
tion before treatment. This includes a
complete past medical history, present
medications, and family history of cancer.

Bilateral mammographic evaluation, with
appropriate magnification views, within
3 months of surgery. The tumor size,
whether
the
mass
is
associated
with
microcalcifications, and the extent of the
calcifications within and outside the mass
should be included in the report.

Accurate histologic assessment of the pri-
mary tumor, including histologic subtype
and
hormone receptor
status.
Thus
a
core-needle biopsy or excisional biopsy
rather than fine-needle aspiration is the
optimum choice for making a tissue diag-
nosis when BCT is considered.

The most difficult part of the evaluation is
the assessment of the patient’s needs and
expectations.
This
requires
that
the
patient and her physician discuss the ben-
efits and risks of mastectomy compared to
BCT in regard to long-term survival, the
possibility and consequence of local recur-
rence, and the impact on cosmetic out-
come and psychosocial adjustment.
Recently, the use of magnetic resonance
imaging (MRI) to determine eligibility for BCT
has become more popular. Proponents state it
can more accurately determine the extent of
the tumor as well as identify multicentricity.
However, the use of MRI is not without contro-
versy. MRI of the breast is highly sensitive, but
has limited specificity (see Chapter 2). As such,
MRI will detect many benign lesions that would
otherwise not preclude breast conservation.
MRI is also limited in its ability to detect ductal
carcinoma in situ (DCIS), which is often a rea-
son why negative margins are not attainable.
Most importantly, many institutions have the
ability to perform MRI but not the technology
to perform MRI-guided biopsy. If a woman
undergoes a preoperative MRI and other lesions
are detected, then she may undergo additional
mammograms or ultrasound to try to identify,
and biopsy, the MRI-detected lesion. However,
if the mammogram and ultrasound are unable
to identify the lesion and MRI-guided biopsy
is not available, the woman is placed in a diffi-
cult position. She can ignore the findings of
the MRI and proceed with BCT (risking inc-
reased recurrence) or proceed with mastectomy
knowing she might have been a suitable candi-
date for breast preservation. Many women nat-
urally choose the latter, and even when MRI-
guided biopsy is available, some women choose
mastectomy rather than go through additional
biopsies. Thus the use of MRI may be leading
to an unnecessary increase in mastectomy rates
without having a significant effect on local
recurrence rates. Further prospective studies
are necessary before MRI can be considered
a routine part of the preoperative staging pro-
cess, and a full discussion of the risks, benefits,
and possible outcomes of preoperative MRI
should be discussed in detail with the patient.
Preoperative MRI may be a reasonable option
in patients who have dense breast tissue, limit-
ing the ability of mammography to detect the
true extent of the cancer or second cancers,
or in women with a high risk of synchronous
cancers (such as women with BRCA mutations)
who desire breast conservation rather than
bilateral mastectomies.
Absolute Contraindications
Multicentricity is an absolute contraindication
to BCT (Box 12–3). This means two or more
tumors are located in separate quadrants of the
BOX 12–3 ABSOLUTE
CONTRAINDICATIONS TO BREAST
CONSERVING THERAPY


Patient does not desire breast
conservation therapy


Unable to receive radiation therapy


First or second trimester of pregnancy
(see Chapter 22)


Collagen-vascular disease


Previous chest wall radiation


Diffuse suspicious microcalcifications on
mammography


Multicentric disease


Inability to achieve negative margins
161
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

breast. In patients with a known breast cancer
and a suspicious lesion on either physical exa-
mination or breast imaging, a biopsy should
be performed on the second lesion before pro-
ceeding with breast conservation, even if this
means an additional procedure. Multicentri-
city is not the same as multifocality, which
implies multiple foci of tumor when examined
histologically. This has more to do with the
pattern of tumor growth. The presence of mul-
tifocality is not a contraindication to BCT, as
long as negative margins can be obtained.
Likewise, the presence of two masses within
the same quadrant may not require mastec-
tomy. This may represent a dumbbell-shaped
tumor. If both masses can be excised in one
excision, this is acceptable if the cosmetic
result
is
reasonable.
On
the
other
hand,
performing more than one lumpectomy for
multiple tumors is associated with high rates
of local recurrence (>30%) and poor cosmetic
outcomes.
The presence of diffuse microcalcifications
on mammography, often described as extend-
ing beyond one quadrant, is another contrain-
dication to breast conservation. These often,
but not always, represent DCIS extending
beyond the invasive cancer. Unfortunately,
the pathology report of the mastectomy speci-
men often does not reveal extensive DCIS
associated with these calcifications, which
can make the surgeon and the patient ques-
tion the need for the mastectomy. However,
the presence of the calcifications not only
may indicate more extensive disease, but also
may make surveillance of the breast for local
recurrence extremely difficult.
Another contraindication is a history of prior
therapeutic irradiation to the breast region,
which when combined with the proposed
treatment would result in an excessively high
total radiation dose to the chest wall. This
includes women who have already been treat-
ed for breast cancer in that breast with radia-
tion and women who have had radiation for
other reasons such as for Hodgkin’s lymphoma
(Fig. 12–2). Prior radiation to other body sites
is not a contraindication. Sometimes in eval-
uating a patient with a history of radiation,
there is a question as to the dose and exact
fields used. In these cases, it is best to obtain
the previous treatment record and consult with
a radiation oncologist before proceeding with
breast conservation.
Pregnancy in the first or second trimester
is an absolute contraindication to the use of
breast irradiation. It may be possible to perform
breast-conserving
surgery
in
the
third
trimester, deferring
breast irradiation until
after delivery. Breast cancer during pregnancy
is discussed in more detail in Chapter 22.
Because lumpectomy and radiation go hand
in hand, one must consider the morbidity of
radiation therapy when one is discussing lump-
ectomy with the patient. Radiation often leads
to fatigue, may lead to skin changes and inflam-
mation of the breast, and can result in a tempo-
rary cough secondary to fibrosis of the lung.
In the long term, radiation can lead to pro-
longed breast edema, shrinkage of the breast
or induration of the cavity, fat necrosis, exces-
sive fibrosis, irradiation pneumonitis, rib frac-
tures, and pleural effusion. Cardiac effects and
radiation-inducedsecondaryneoplasmsarealso
a concern. These are discussed in more detail in
Chapter 15. However, it is important that the
surgeon be able to discuss these with the patient
when presenting the choice between BCT and
mastectomy. On the other hand, the surgeon
must be careful not to present mastectomy as
“a way to avoid radiation”; depending on the
pathology results, postmastectomy radiation
may still be recommended.
Relative Contraindications
Some oncologists consider connective tissue
disease to be an absolute contraindication to
breast conservation because many of these
patients tolerate irradiation very poorly. How-
ever, most consider it a relative contraindica-
tion, depending on the type of connective
tissue disease and the relative risks and bene-
fits of therapy. Scleroderma is an absolute con-
traindication. Systemic lupus erythematosus
patients may also have a poor reaction to radi-
ation therapy. For other types of collagen-
vascular disease, such as Raynaud phenomenon,
rheumatoid arthritis, Sjo¨gren’s syndrome, or
polymyositis, the response to radiation has
not been as severe, and these patients may still
be considered for BCT.
Cervical
Supraclavicular
Mediastinal
Mantle
field
Axillary
Lymph nodes
Figure 12–2. The field of radiation (including the
mantle field) for Hodgkin’s disease. (From Roses D.
Breast Cancer. Philadelphia: Elsevier, 2005.)
162
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

The ideal candidate for breast conservation
is the patient with T1 or T2 tumors and a
breast large enough to encompass an adequate
resection. However, this is subjective and size
is not an absolute contraindication. Women
with large breasts can undergo resection of a
4- or 5-cm tumor with a good cosmetic result
and successfully undergo breast irradiation,
although they may require radiation in the
prone position to assure reproducibility of the
patient set-up. Patients with large tumors
who still want breast conservation may con-
sider neoadjuvant chemotherapy to down-
stage the tumor (see Chapter 18).
Finally, there is the question of microscopic
negative margins. Often described as a con-
traindication to BCT is the inability to obtain
negative margins. If after a reasonable attempt
at reexcision there are still diffusely positive
margins, then a mastectomy is indicated. It is
ideal that negative margins be obtained before
proceeding to radiation, because the majority
of studies have demonstrated a lower local
recurrence rate with negative compared to posi-
tive margins. The impact of a close margin is less
clear, and the decision whether to reexcise must
be made on a case-by-case basis, taking into
consideration the radiation planned and the
use of systemic therapy. Close margins, which
have been associated with an increased risk of
recurrence in some series but not in others.
Not Contraindications
There are several features that may be associated
with an increased risk of recurrence, but are not
necessarily contraindications to breast conser-
vation (Box 12–4). The most commonly mis-
quoted contraindication is the presence of
axillary nodal metastases, whether these are
clinical or pathologic. Given the increased like-
lihood of systemic disease when the lymph
nodes are positive, the impact of local control
on overall survival diminishes. In addition, the
risk of chest wall recurrence after mastectomy
increases with the number of positive axillary
lymph nodes. This is not true for breast con-
servation, possibly due to the use of radiation
therapy. This is why chest wall radiation is con-
sidered after a mastectomy when the axillary
nodes are positive (see Chapter 15).
Age is not a contraindication to BCT; physi-
ologic age and the presence of comorbid con-
ditions should be the primary determinants
of local therapy in older women. It is also
obviously wrong to assume that an older
woman would be less concerned with her
physical
appearance
or
the
effects
of
a
mastectomy on her sexual image. Likewise,
being young is not a contraindication. Even
though some series have shown a higher risk
of relapse in young women (defined as either
younger than 35 or 40), some of these series
have also shown that younger women have
worse prognosis lesions (high grade, vascular
invasion, ER-negative tumors) and a greater
likelihood of distant disease.
Histologic subtypes other than invasive ductal
carcinoma (e.g., invasive lobular cancer) are not
associated with an increased risk of breast cancer
recurrence, nor is the presence of an extensive
intraductal component. This is defined as an
invasive cancer associated with a large compo-
nent of intraductal cancer (>25%) within the
tumor and in the surrounding breast tissue. Both
lobular carcinomas and noncalcified DCIS may
extend beyond what is visualized on imaging
studies, so it may take a wider lumpectomy or a
reexcision to obtain negative margins. However,
if negative margins can be obtained, then breast
conservation is reasonable.
As with tumor size, tumor location must be
considered on a case-by-case basis and is not in
itself a contraindication to breast conservation.
The surgeon should discuss with the patient the
cosmetic implications of the position of the
lumpectomy. Tumors in the 6-o’clock position
BOX 12–4 VARIABLES NOT
CONSIDERED TO BE
CONTRAINDICATIONS TO BCT
Variables Associated with an
Increased Risk of Recurrence after
Breast Conservation


Tumor size


Positive or close margins


High grade


Angiolymphatic invasion


Excessive delay in radiation (>16 weeks)


Young age (may be associated with
higher grade or may be associated with
surgeon willingness to compromise
margins for cosmetic purposes)
Variables Associated with a Decreased
Likelihood of Negative Margins but No
Difference in Recurrence If Negative
Margins Are Obtained


Extensive intraductal component,
defined as greater than 25% or more of
the tumor composed of ductal carcinoma
in situ both within and at the periphery
of the margin


Lobular carcinoma
163
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

of the breast will often cause downturning of
the nipple after therapy. Tumors in the superfi-
cial subareolar location may require resection
of the nipple-areolar complex to achieve nega-
tive margins. The patient and her physician
need to assess whether each resection, and the
effect on cosmesis, is preferable to mastectomy
and reconstruction.
Breast implants previously placed for augmen-
tation are not an absolute contraindication to
lumpectomy. If a lumpectomy can be performed
without violating the basic principles (complete
tumor excision, accurate lymphatic mapping),
then radiation can be delivered to the breast
using standard techniques and doses. However,
capsular contracture is a risk, causing the breast
to become rounded, firm, and retracted upward.
The suitability of BCT in women with breast
implants in part depends on how the implant
was placed. For example, if the implant was
placed through an axillary incision, this may
impact the accuracy of sentinel lymph node
biopsy. Subcutaneous implants have a higher
rate of capsular contraction with radiation than
subpectoral. If negative margins cannot be
obtained secondary to the tumor being in close
proximity to the implant (cancers sometimes
invade the fibrous capsule around the implant),
the implant may need to be removed.
Finally, the patient’s individual risk of devel-
oping a second cancer is not a contraindication
to breast conservation, although a discussion
should be held with these patients of their
increased risk of a second breast cancer and
the potential benefits of bilateral mastectomy.
Thus breast cancer patients with a strong fam-
ily history of breast cancer or with a known
BRCA1 or BRCA2 mutation may opt for bilat-
eral mastectomy; if they are not ready for that,
then unilateral mastectomy as treatment of
the known cancer is not warranted if they are
candidates for, and desire, BCT.
Operative Management
of Breast Cancer
Lumpectomy
Placement of the Incision
Lumpectomy may be performed either under
general anesthesia or intravenous sedation with
local anesthesia. The patient is placed supine
on the operating room table and the entire
breast and axilla is prepped and draped in an
aseptic
fashion.
For
a
lumpectomy,
the
incision should ideally be placed directly over
the mass. Excessive tunneling is not recom-
mended because this may compromise margins
and make a reexcision for positive margins
unnecessarily difficult. Circumareolar incisions
result in a superb cosmetic outcome and are
appropriate for lesions located near the areola,
but care should be taken in tunneling too far
simply to use a circumareolar incision.
In the upper hemisphere of the breast, inci-
sions should be curvilinear, following the nor-
mal lines of tension in the skin (Fig. 12–3). It is
not necessary to routinely excise skin with the
specimen; however, if the tumor is close to
the skin, an ellipse over the tumor should be
taken to ensure a negative anterior margin.
In the lower hemisphere of the breast, either cur-
vilinear incisions or radial incisions can be used.
For small tumors in relatively larger breasts,
where it will not be necessary to remove over-
lying skin and adequate breast parenchyma
will
remain
around
the
cavity,
curvilinear
Figure 12–3. Planning the lumpectomy incision.
Skin incisions should be placed within the Langer’s
lines when possible. Closer to the areola, circumar-
eolar incisions are appropriate, but excessive tunnel-
ing should be avoided. In the lower hemisphere of
the breast, radial incisions should be strongly con-
sidered, because these result in less distortion of
the nipple-areolar complex. (From Roses D. Breast
cancer. Philadelphia: Elsevier, 2005.)
164
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

incisions are acceptable. Otherwise, radial inci-
sions should be used. Curvilinear incisions
beneath the areola, where skin or a good amount
of breast tissue is removed, will distort the breast
in a way that the breast collapses inferiorly and
the nipple points downward, resulting in an
unacceptable cosmetic outcome. However, one
must keep in mind how this would ultimately
impact a mastectomy incision (particularly a
skin-sparing mastectomy incision) in case the
attempt at breast conservation fails (Fig. 12–4).
The decision to use circumareolar or radial inci-
sions in the lower hemisphere of the breast must
be individualized to the patient, taking into
account the size of the tumor, the size of the
breast, and the pathology.
When the cancer is located in the upper outer
quadrant of the breast, it may seem attractive
to perform the sentinel lymph node biopsy or
the axillary lymph node dissection through
one longer incision. Even though this may
be acceptable when the tumor lies high in the
axillary tail of the breast, it should generally
be avoided. It may result in a long suture line
across normal skin creases, which leads to
excess contraction and deformity. In addition,
it complicates the planning and delivery of
a boost to the tumor bed for the radiation
oncologist. Thus two separate incisions for the
lumpectomy and for the axilla are preferable,
even if they are only 2 to 3 cm apart.
Lumpectomy
After creation of the skin incision, skin flaps
are raised over the tumor. It is important that
these skin flaps not be too thin. Thin flaps will
result in excessive retraction of the cavity dur-
ing radiation, resulting in a concavity at the
site of the lumpectomy. On the other hand,
thick flaps heal much better. The subcutane-
ous fat helps support the skin, and if left
intact, helps preserve the natural contour of
the breast (Fig. 12–5). For deep-seated tumors,
after incising the skin, the breast tissue may
be divided straight down to approximately
1 cm above the tumor mass before beginning
the dissection around the tumor. For interme-
diate masses, the skin flaps should be created
at a 45-degree angle. For more superficial
lesions, an adequate amount of skin overlying
the tumor should be taken so that thin skin
flaps are not necessary for adequate margins.
Once appropriate flaps are raised peripher-
ally around the tumor, the dissection should
continue straight down toward the chest wall.
The surgeon should keep one hand on the
tumor at all times during the dissection to
ensure adequate margins. A rim of normal
breast tissue or fat of approximately 1 cm
should be excised with the tumor centered in
the specimen. The incision should be large
enough to allow this. Removing a tumor
A
B
C
Figure
12–4. As
with
exci-
sional biopsies, a subsequent
mastectomy should be consid-
ered if the attempt at breast
conservation fails. (From Bland
KI, Copeland EM III. The breast,
3rd ed. Philadelphia: WB Saun-
ders, 2004.)
165
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

through a small incision requires excessive
manipulation of the tumor and an increased
risk of positive margins on final pathology.
Limiting yourself in an attempt to keep the
incision small increases the need for a reexci-
sion lumpectomy, which will have a worse cos-
metic outcome than if the skin incision was
simply lengthened. Excising even a small
ellipse of skin with the tumor often allows
for a wider operative field to work in. As the
mass is freed peripherally, the tumor is grasped
and retracted upward so that the posterior
aspect may be completed. Exposure is aided
by using small retractors. For deeper tumors,
the pectoralis fascia should be included in the
specimen. A portion of the pectoralis muscle
should be included for very deeply situated
tumors to ensure an adequate deep margin.
By working peripherally around the tumor
and waiting until the tumor is circumferen-
tially free to grasp the mass, the surgeon
avoids excessive manipulation of the tumor.
This is important because increased manipu-
lation increases the likelihood of removing
surrounding fat and tissue from the cancer.
Exposing
the
tumor
through
excess
manipulation results in ink approximating
the
cancer,
and
a
pathologic
finding
of
a positive margin, necessitating reexcision.
When needed, a clamp can be used to grasp
the normal tissue around the mass to assist in
retraction, but care should be taken not to pull
too aggressively. A clamp should never be
placed directly on the tumor.
The lumpectomy may be performed with a
scalpel, scissors, or cautery. Many surgeons
prefer cautery to maintain hemostasis through-
out the dissection, increasing visibility. How-
ever, the cautery effect on the specimen may
obscure the ability of the pathologist to read
the margins. Sharp dissection results in a
clearer margin status and, with appropriate
technique and retraction, bleeding can be kept
to a minimum. Additional time can be taken
once the specimen is out to ensure hemostasis.
As the tissue is removed from the lum-
pectomy cavity, it is important to note and
maintain its orientation. Marking sutures are
immediately placed on the specimen. A single
stitch superiorly, a long stitch laterally, and a
double stitch deep is an easily recalled method
to orient the tissue the same way each time,
and preprinted stickers can be created for the
circulating nurse (Fig. 12–6).
If there is any concern clinically regarding
the adequacy of any margin, an additional
specimen can be taken from the wall of the
lumpectomy cavity corresponding to the point
opposite the area of concern. With the skin
retracted anteriorly, the wall is grasped with
a toothed pick-up or clamp and a new, ade-
quate margin is obtained. This should be
Figure
12–5. Preserving
the
subcutaneous
fat
between the skin and the tumor helps avoid exces-
sive skin retraction and indentation. (From Bland KI,
Copeland EM III. The breast, 3rd ed. Philadelphia: WB
Saunders, 2004.)
Long stitch:
lateral
Short stitch:
superior
Double stitch:
deep (posterior)
Figure 12–6. The lumpectomy specimen should be
oriented in three planes so that the pathologist can
use a multicolor staining system to identify close or
positive margins.
166
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

liberal, taking a generous portion of the wall of
the cavity to ensure the margin of concern is
truly excised. Otherwise, the pathologist may
state that you obtained negative margins, but
in reality left behind a close or positive mar-
gin. The new specimen should be marked
appropriately with sutures so that the patholo-
gist knows what the true margin is.
Wound Closure
After completion of the lumpectomy, hemosta-
sis should be achieved to avoid a hematoma.
Drains are never used after a lumpectomy. The
surgeon should also never try to simply reap-
proximate the breast tissue. For large defects,
there are methods to mobilize adjacent tissue
(see later), but in general sutures should not be
placed in the breast parenchyma to close the
cavity. The lumpectomy cavity will fill with ser-
oma and fibrin, and ultimately fibrous tissue,
which maintains the normal, rounded contour
of the breast.
Once hemostasis is achieved, surgical clips
should be placed within the lumpectomy cavity
in the six anatomic locations (anterior, poste-
rior, medial, lateral, superior, inferior). This
helps in the planning of the radiation therapy,
specifically if a boost is planned or if partial
breast irradiation is contemplated. The incision
should then be reapproximated with absorb-
able deep dermal sutures followed by a subcuti-
cular stitch or tissue adhesive. Interrupted
nylon or silk sutures leave cross-hatching scars
and are not necessary.
Wire-Localized Lumpectomy
With the increased use of screening mammogra-
phy, many cancers are diagnosed by means of a
stereotactic core biopsy of a mammographic
abnormality. In these cases, a wire-localized
lumpectomy will be necessary. Localization
involves placing a rigid introducer needle with
a flexible hooked wire inside of it at the site
of the abnormality using either biplanar mam-
mography or ultrasound (Fig. 12–7). Ultrasound
is relatively simpler and more comfortable for
the patient. In many cases, the original abnor-
mality is gone, removed by the core-needle
biopsy, and so a clip left by the radiologist is
localized for excision.
Once the rigid needle is in place, it is with-
drawn, leaving the hooked wire in place. The
hook keeps the wire in place so it is not easily
moved, although the external wire should still
be secured to the skin so that it is not
dislodged as the patient travels from radiology
to the operating room. The craniocaudal and
mediolateral views of the wire in place accom-
pany the patient to the operating room.
The wire-localized lumpectomy is similar to
the wire-localized biopsy except the surgeon
is attempting to obtain negative margins. In
some cases, more than one wire may be placed
to bracket the mass or calcifications to give
the surgeon a better idea of what needs to be
excised to obtain negative margins. As with
standard lumpectomy, an adequate skin inci-
sion should be used to allow adequate room
to excise the entire region and not overly
manipulate the tissue. The incision should be
curvilinear in Langer’s lines, and created with
a subsequent lumpectomy or mastectomy in
mind. The incision should be placed over
the abnormality and not routinely made at the
site of wire entry. The surgeon should use the
wire and images to determine the site of
the abnormality and place the incision directly
over this.
The direction of the dissection is determined
by the lesion size, direction of the wire, and the
relative proximity of the wire to the lesion
(Fig. 12–8). Wires placed just posterior to the
lesion are helpful because the surgeon removes
the lesion by staying deep to the localization
needle. Once the incision is made, it is then
necessary to identify the shaft of the lesion
and retract it into the wound. Dissection in
the plane facing the wire entry site allows for
simple detection of the wire. Once identified,
it is secured at the site of the parenchyma and
the distal end of the wire is brought out into
the wound. Failure to adequately secure the
wire may result in accidental dislodgment.
Once out, the tissue is grasped with an Allis
clamp. It is preferable to grab the tissue near
the wire but not the wire itself because pulling
too hard on the clamp may pull the wire from
the specimen. Resection of the tissue sur-
rounding the wire proceeds. The relationship
between the wire and the lesion, as demon-
strated on mammography, helps guide how
much tissue to take.
Immediately upon removal of the specimen,
it is held in anatomic position and marked with
orientation sutures. It is also helpful to place
clips at the periphery of the specimen to allow
for orientation of the specimen radiograph.
These may help guide the excision of additional
tissue of the lesion if there is any concern of
a close radiographic margin. The specimen is
sent to radiology for confirmation that the
lesion in question was removed. If there is any
167
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

A
B
C
Figure 12–7. A and B, Mediolateral and craniocaudal views from wire localization using superior approach.
C, Specimen radiograph demonstrates abnormality adjacent to the reinforced portion of the hookwire. Pathol-
ogy demonstrated ductal carcinoma in situ. (Images courtesy of Dr. Alexis Nees, Department of Radiology,
University of Michigan.)
168
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

clinical concern of a close or positive margin,
that should be excised as a separate specimen.
The specimen radiography may also suggest a
margin that appears close and requires reexci-
sion. Because wire-localized lumpectomies tend
to have a higher rate of close or positive mar-
gins than lumpectomies for palpable masses, a
more generous approach to reexcising margins
at the first operation is warranted.
Reexcision Lumpectomy
Reexcision lumpectomy should be performed
in any patient with unknown or positive mar-
gins. It is also strongly recommended in patients
with close margins, approximately 2 to 3 mm.
Reexcision is necessary in one fourth to one
third of lumpectomies. Failure to reexcise close
or positive margins stands a high chance of
leaving residual disease and increases local
recurrence rates.
The standard approach to a reexcision lump-
ectomy is to remove the entire cavity. An ellipse
of skin is drawn around the previous skin inci-
sion so that the previous scar is removed with
the specimen. Skin flaps are then raised. The
previous cavity is usually readily palpable, and
the approach to the reexcision is similar to that
of a lumpectomy. As with a lumpectomy, the
surgeon should keep one hand on the cavity
at all times during the dissection to ensure
adequate margins. It is important not to violate
the cavity because this complicates the inking
and evaluation of the new margins.
This approach is necessary when the initial
lumpectomy was not oriented and inked with
the six-color system. In this setting, the sur-
geon does not know where the close or posi-
tive margins are, so the entire cavity needs to
be excised. This approach, however, results in
a large volume of resected breast tissue, often
beyond what is necessary to achieve negative
margins. If the original lumpectomy was ori-
ented and the margin in question is known,
an alternative approach might be to enter the
previous biopsy cavity and excise only the
involved margin. This minimizes the volume
of tissue excised, and studies have shown that
this approach is oncologically sound, with no
increased risk of local recurrence. This stresses
the importance of orienting and using the
six-color inking system on all breast biopsies
and lumpectomies.
To reexcise just the involved margin, the
previous incision may be excised completely
or reopened using a scalpel. The seroma fluid
is suctioned out. If too much time elapses
between the original lumpectomy or biopsy
and the reexcision lumpectomy, the cavity
may no longer be evident. In this case, it is
preferable
to
excise
the
entire
cavity
as
described earlier. However, if there is still a cav-
ity, the margin in question can be grasped at
the top with an Allis forceps and that margin
Hooked
wire cut to
manageable
length
Site of wire
entry into
breast
Skin incision
Lesion
Wire has been
delivered into
operative field
Hemostats
place tension
on stay suture
Nonpalpable
carcinoma
Figure 12–8. The wire-localized lumpectomy. The placement of the incision and direction of the dissection
are determined by the lesion size, direction of the wire, and the relative proximity of the wire to the lesion.
Once the incision is made, it is best to identify the shaft of the wire and retract it into the wound. Once out,
the tissue is secured and resection of the tissue surrounding the wire proceeds. (From Roses D. Breast cancer.
Philadelphia: Elsevier, 2005.)
169
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

reexcised to a depth of approximately 1 cm.
The entire hemisphere in question should
be reexcised because it is not possible to know
precisely where the margin was involved.
A positive lateral margin may have been at
the anterior-lateral margin, posterior-lateral
margin, superior-lateral margin, or inferior-
lateral margin. Depending on the pathology
report, more than one margin may need to
be excised.
Lumpectomy in the Prosthetically
Augmented Breast
With the increased popularity of breast aug-
mentation, surgeons are increasingly facing
the management of a breast cancer within an
augmented breast. Many surgeons have rou-
tinely recommended mastectomy in this sit-
uation, with reconstruction to be performed
immediately or at a later date. Arguments for
this include fear of rupture of the implant, the
need to radiate the implant, and the impact of
the implant on mammographic surveillance.
However, mastectomy is not absolutely indi-
cated in this situation. Several series describe
reasonable outcomes in patients who under-
went BCT in the face of a previously placed
implant. Several factors must be considered. It
is true that capsular contraction will occur
with radiation of the implant, no different than
in women who undergo implant reconstruc-
tion followed by chest wall radiation. While
rates of contracture are higher, this may still
be an acceptable alternative to mastectomy.
This is particularly true if the implant was
placed submuscularly rather than subcutane-
ously. The size of the tumor and the ability of
the surgeon to obtain negative margins with-
out injuring the implant must also be consid-
ered. Careful attention should be paid to
treatment technique, both surgical and radia-
tion, and a balanced discussion must be held
with the patient regarding the impact on cosm-
esis. However, in appropriately selected patients,
BCT is a reasonable option in the face of prior
augmentation.
Postoperative Care after Lumpectomy
The morbidity of a lumpectomy is relatively
minimal. The most common complications
are seroma, hematoma, and infection. Seromas
are frequent but often cause no difficulty for
the patient; if they are symptomatic, they are
relatively easy to manage by needle aspiration.
Hematomas and infection are relatively rare.
Both are typically managed conservatively,
although incision and drainage is sometimes
necessary. Altered sensation to the nipple can
also occur depending upon the location of
the incision.
The use of a support brassiere in the postop-
erative period bolsters efforts to sustain hemo-
stasis and relieves tension on the skin closure
imposed by the weight of the breast. This can
be especially important with large, pendulous
breasts, in which blood vessels running along-
side the cavity can be avulsed mechanically if
the heavy breast is allowed to suspend unsup-
ported. The patient should be encouraged to
wear the support brassiere day and night for
several days.
Simple Mastectomy
After the induction of general anesthesia, the
patient is positioned supine with the arm
abducted to 90 degrees and secured to an arm-
board. To avoid a brachial plexopathy related
to stretch injury of a malpositioned patient,
the American Society of Anesthesiology recom-
mends upper extremity positioning such that
the arm is no greater than 90 degrees, with
neutral forearm position, and use of padded
armboards. The chest, axilla, and upper arm is
prepped and draped in sterile fashion. The prep
should extend sufficiently beyond the breast so
that the landmarks can be easily identified;
across the midline, to the costal margin, the
base of the neck, and laterally to the operating
room table.
The standard incision for a mastectomy is an
elliptical skin incision including both the nip-
ple-areolar complex and the previous biopsy
incision. The ellipse may be oriented either
transversely or obliquely. The choice of inci-
sion must be based on the size of the breast,
body habitus of the patient, and size and loca-
tion of the tumor (or biopsy cavity). Care
should be taken to make the ellipse wide
enough
that
redundant
skin
is
avoided,
including dog-ears, but not so wide that the
closure is excessively tight. Undue tension
may lead to vascular compromise of the flaps.
Bear in mind that the patient’s back is per-
fectly straight on the operating room table,
something that is rarely maintained normally,
so what seems tight will be less so once the
patient is awake. The ideal ellipse has equal
lengths of the superior and inferior lines. This
may be facilitated by using a silk suture on a
hemostat to measure both lines.
170
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

There are several options for how this ellipse
is oriented. The classic Stewart incision results
in a transverse scar (Fig. 12–9). It should begin
at the lateral margin of the sternum and end
at the anterior margin of the latissimus dorsi.
The Stewart incision may be modified to lie
obliquely, so the final incision extends supe-
riorly at the lateral margin. The Stewart inci-
sion is particularly good for central tumors,
although it may be applicable for most tumors.
It is often preferred by plastic surgeons when
delayed reconstruction is planned, especially if
postmastectomy radiation is to be employed.
The other popular incision is the Orr oblique
incision. As opposed to the modified Stewart
incision, which extends slightly superiorly in
the lateral margin, the Orr incision is an oblique
incision (Fig. 12–10). This approach is ideal for
upper, outer quadrant incisions but, as with the
Stewart incision, can be used for most tumors.
Other less common variations may be appro-
priate for tumors in other quadrants. Alterna-
tively, a skin-sparing incision should be used
when immediate reconstruction is planned
(Fig. 12–11). The skin-sparing mastectomy is
described in more detail in Chapter 14.
In addition to marking the elliptical inci-
sion, the boundaries of the breast should be
marked preoperatively. These include the lat-
eral margin of the sternum medially, the
second rib superiorly, and the inframammary
crease. This provides guidance as to how far
to raise the flaps, which and can sometimes
be lost during the operation.
The skin incision is then made with a scal-
pel, dividing the skin and superficial fascia
just until the breast tissue is evident. Several
superficial veins need to be cauterized. Once
the skin incision is completed, the superior
flap is raised.
The key to raising the skin flap is adequate
retraction (Fig. 12–12). Although several instru-
ments may be used to grasp the skin (Adair
clamps, skin hooks, temporary silk sutures
placed in the dermis), it is imperative that they
be placed evenly along the flap and the retrac-
tion is directly anterior. It is not uncommon
for the assistant to retract the flap anteriorly
and superiorly. This allows the assistant a better
view of the dissection but distorts the view of
the surgeon and greatly increases the chance
of being too close to dermis or even going
through the skin. With the assistant retracting
straight up, the surgeon pulls the breast tissue
away from the flap with the opposite hand.
A gauze pad should be kept on the breast tissue
to not only prevent the hand from slipping but
also maintain hemostasis if sharp dissection is
used. This is the key maneuver during a mastec-
tomy and the most common error by junior
1-2 cm
Figure
12–9. The
classic
Stewart elliptical mastectomy
incision. The medial aspect is
at the lateral edge of the ster-
num
and
the
lateral
aspect
overlies the latissimus dorsi
muscle. (From Bland KI, Cope-
land EM III. The breast, 3rd ed.
Philadelphia:
WB
Saunders,
2004.)
171
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

residents when learning the procedure. The
surgeon should be continuously repositioning
the opposite hand closer to the plane between
the breast and the flap, as well as assessing the
thickness of the flap.
With the right retraction by both the sur-
geon and the assistant, the plane is readily
apparent. Skin flaps should be elevated at the
subcutaneous tissue level, not the subdermal
level. This preserves the subcutaneous vascular
plexus, which nourishes the overlying skin.
Done properly, this can be relatively bloodless.
The flap can be raised by the use of a scalpel,
scissors, or cautery depending on the surgeon’s
preference. Several studies have compared scal-
pel to cautery, both retrospectively and pro-
spectively, and found little difference with the
exception of blood loss, which is lower with
electrocautery. If cautery is used, it should not
be maintained in one position for too long a
period of time to avoid thermal injury to the
flap. Once in the right plane, the superior flap
can be developed quickly to the level of the
subclavius muscle, from the lateral aspect of
the sternum to the lateral edge of the pectoralis
major and axillary fascia. The inferior flap is
then raised in an identical manner to the infra-
mammary crease. If the white undersurface of
the dermis is seen, the subcutaneous plexus
1-2 cm
Figure 12–10. The classic Orr oblique ellip-
tical mastectomy incision. (From Bland KI,
Copeland EM III. The breast, 3rd ed. Philadel-
phia: WB Saunders, 2004.)
Axillary incision
Deep tumor
Incision scar
Reexcision
with 1-cm margin
Nipple areolar
incision
Figure 12–11. Skin-sparing mastectomy incisions
incorporating the previous scar and nipple-areolar
complex while preserving as much skin as possible.
A separate incision is used for the lymph nodes.
(From Bland KI, Copeland EM III. The breast, 3rd ed.
Philadelphia: WB Saunders, 2004.)
172
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

has been injured and there may be a question
of flap viability. This is usually not a problem
if immediate reconstruction is not planned,
but may lead the plastic surgeon to delay
reconstruction to a later date. As the inferior
flap is raised, the inframammary crease is lost.
This is why it is important for the surgeon to
mark the crease preoperatively and to not go
past this line while raising the inferior flap.
With the borders of the breast identified cir-
cumferentially, it is time to remove the breast.
The breast and fascia is dissected off of the pec-
toralis major muscle. The plane is started at
the cephalad portion of the breast. The breast
is retracted inferiorly and the plane is devel-
oped. It may be helpful to grasp the superior-
most aspect of the breast with clamps to assist
with retraction when first developing the plane.
The dissection proceeds inferiorly. The cautery
should be moved parallel to the fibers of
the pectoralis major muscle as the breast is
removed. Small perforator vessels should be
grasped with a pick-up and cauterized as they
are identified. Medially, there are some larger
perforating branches of the internal mammary
vessels. If these are bleeding, it is important
not to try to directly cauterize them, but rather
to grasp them with a pick-up or hemostat first
because they sometimes retract beneath the
muscle and can be difficult to control. If this
is the case, they can easily be controlled with
a figure-of-eight suture ligation. Excessive cau-
tery or dissecting against the direction of the
fibers (with lateral retraction of the breast) can
cause separation of the pectoralis from the
sternum, which can impact immediate recon-
struction (see later). In addition, chasing these
bleeding vessels deeper could lead to pneumo-
thorax if the parietal pleura is violated.
While removing the breast, it is easy to slip
from the plane between the muscle and the
fascia, into the plane between the breast and
the fascia, leaving the fascia behind. It is
important to remove the fascia with the speci-
men to ensure an adequate resection. As the
surgeon
moves
inferiorly,
the
breast
is
removed from the pectoralis, and the serratus
anterior muscle is exposed. In contrast to the
pectoralis, the fascia over the serratus anterior
should be left intact, and care should be taken
not to injure this muscle. If the patient is to
undergo immediate reconstruction with an
expander, these will be placed within a pocket
beneath the pectoralis muscle, with closure to
the serratus fascia to provide soft tissue cover-
age of the implant or expander. Injury to the
pectoralis medially, or the serratus anterior
inferiorly, compromises the ability to provide
Figure
12–12. Elevation
of
skin flaps during a mastec-
tomy using Metzenbaum scis-
sors. (From Bloom N, Beattie E,
Harvery J. Atlas of cancer sur-
gery.
Philadelphia:
Elsevier,
2000.)
173
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

adequate coverage and may force the plastic
surgeon
to
abandon
plans
for
immediate
reconstruction. Even if immediate reconstruc-
tion is not planned, these mistakes can still
complicate delayed reconstruction, and proper
technique should be employed in all cases.
Although no axillary dissection is planned
as part of a simple mastectomy, the lateral
aspect of the breast is traditionally the last part
of the breast to be removed. Once the lateral
border
of
the
pectoralis
major
muscle
is
cleared, the axillary fascia is evident, marking
the transition from the breast tissue to the
axillary fat, and the mastectomy is completed.
It is important to not terminate the mastec-
tomy before encountering the axillary fascia,
so that the axillary tail is not left behind.
Sutures are placed to orient the breast before
sending it off the operative field.
After the breast is removed, hemostasis is
assured and the field is irrigated with copious
amounts of warm saline. The skin margins are
examined for any areas of devascularization.
Any concerning areas should be debrided before
closure. Through a separate stab incision in the
inferior flap along the anterior axillary line, a
single 10-French closed-suction Silastic catheter
is placed along the inferomedial aspect of the
wound bed to drain the space between the
skin flaps and chest wall. This is secured in place
with a 2-0 nonabsorbable suture. The wound
is aligned and the deep dermal layer closed
with interrupted 3-0 absorbable synthetic suture.
A subcuticular 4-0 absorbable suture is then used
to close skin, although tissue adhesives are gain-
ing popularity. Suction catheters are connected
to bulb suction.
One frustrating aspect of the mastectomy,
particularly in heavyset patients with thick
axillary fat pads, is “dog-ears,” the triangular
or cone-shaped flaps of redundant skin and
fatty tissue at the ends of the incision. These
are usually more prominent at the lateral
aspect of the mastectomy incisions. Frequently
the incisional dog-ear will not be readily appar-
ent while the patient is lying supine on the
operating room table, but when she sits or
stands upright postoperatively, these unsightly
protrusions become obvious. These can be
quite uncomfortable for the patient because
the upper arm rubs against them. If recognized
intraoperatively,
there
are
several
surgical
approaches to eliminate dog-ears. Sometimes
the redundant axillary skin and fatty tissue can
be resected by elongating the standard elliptical
mastectomy wound. However, this often length-
ens the scar while only moving the dog-ear more
laterally. It is better to excise the tissue using a
broad “tear-drop” incision, with the point of
the tear-drop oriented medially. Another option
is to bring the redundant axillary tissue forward
and create a “T” or “Y” configuration at the lat-
eral aspect of the transverse mastectomy inci-
sion. When the dog-ear cannot be reasonably
corrected at the time of surgery, or if it is not
recognized in the supine position but becomes
apparent in the postoperative setting, the best
solution is to resect it at a later date in the outpa-
tient setting.
Modified Radical Mastectomy
The MRM is becoming a less commonly used
operation with the increased use of breast con-
servation and the decreased need for axillary
dissection in the era of sentinel lymph node
biopsy. Today, the MRM is used primarily for
women who require or desire mastectomy
and have documented nodal metastases.
After the induction of general anesthesia,
the patient is positioned supine with the arm
abducted
to
90
degrees
on
an
armboard
(Fig. 12–13). Unlike the simple mastectomy,
the arm is not secured to the armboard for
the MRM so that it may be brought into the
operative field during the case. The chest,
axilla, and entire arm are prepped and draped
in sterile fashion. The prep should extend suffi-
ciently beyond the breast so that the landmarks
can be easily identified: across the midline, to
Figure 12–13. Patient position for a right modified
radical mastectomy. The patient is positioned supine
with the arm out at 90 degrees, never hyperex-
tended. The entire arm is prepped to the wrist and
the shoulder and lateral chest are prepped down to
the table. The armboard is covered with a sterile
drape and the arm sheathed to above the elbow with
a sterile impervious stockinet, keeping it within the
sterile field. (From Bland KI, Copeland EM III. The
breast, 3rd ed. Philadelphia: WB Saunders, 2004.)
174
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

the costal margin, the base of the neck, and
laterally to the operating room table, including
around the shoulder. The forearm and hand
are isolated in a stockinet dressing wrapped
with a Kerlix roll.
The incision for the MRM is the same as for
a simple mastectomy. It is not necessary to
extend the incisions further into the axilla; a
complete axillary dissection can be performed
through the standard incisions. A skin-sparing
mastectomy can still be performed when an
MRM is necessary. In addition to the incision
around the nipple-areolar complex, with a
keyhole extension laterally, a second incision
is made in the axilla to complete the axillary
dissection.
After the patient has been marked, the supe-
rior
and
inferior
skin
flaps
are
raised
as
described for the simple mastectomy, and the
procedure follows the same steps except for
the lateral margin. As the lateral aspect of the
inferior flap is completed, it is an ideal time
to identify the latissimus dorsi muscle because
this landmark is crucial to defining the borders
of the axilla. Once identified, this can be
cleared superiorly along the anterior border of
the muscle. Dissecting medially along the
muscle may result in injury to the thoracodor-
sal bundle.
The breast and fascia are removed from the
pectoralis major muscle as described earlier
(Fig. 12–14). As the breast is removed from the
lateral border of the pectoralis major muscle,
the space between the pectoralis major and
minor muscle can be developed so that palpa-
tion of the interpectoral (Rotter’s) nodes can
be undertaken (Fig. 12–15). Some surgeons only
remove this tissue when palpable nodes are
detected; other surgeons routinely include the
fibroareolar tissue in the interpectoral space,
which can be swept laterally and included with
the specimen. However, excessive dissection in
this area can lead to injury of the lateral pectoral
nerve and is unlikely to be of added benefit if
grossly involved nodes are not present. The
axillary nodes are then removed en bloc with
the breast. The steps of the axillary dissection
are outlined in Chapter 13.
Once the breast and axillary contents are
removed, the closure is the same as for a sim-
ple mastectomy, except two closed-suction
drains are typically placed through two differ-
ent stab incisions. In addition to one drain
along the inferomedial aspect of the chest
wall, a second drain is laced in the axillary
space. The tip of the drain should be 2 cm
below the axillary vein and should lie on the
ventral surface of the latissimus dorsi.
Postoperative Care
The patient should be given a binder with ade-
quate fluffs to provide adequate but not exces-
sive compression. Tight pressure dressings are
Pectoralis
major
Fascia
Figure
12–14. Elevation
of
the breast and pectoralis major
fascia off of the underlying
muscle. Dissection should pro-
ceed superior to inferior and
medial to lateral. (From Bloom N,
Beattie E, Harvery J. Atlas of
cancer
surgery.
Philadelphia:
Elsevier, 2000.)
175
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

not necessary. The dressings should remain
undisturbed for 48 to 72 hours after the sur-
gery, unless concerns for flap viability warrant
taking down the dressings to examine the
flaps. Patients are encouraged to sit upright
and avoid slouching so as to avoid excessive
skin flaps. Range-of-motion exercises for the
arm and shoulder are given to the patient pre-
operatively, with instructions to begin them
on day 1. Particularly in the case of the
MRM, it is important for the patient to use
her arm rather than keep it at her side in a
sling because this will lead to stiffening of
the shoulder and limited range of motion.
The drains remain in place until the output
drops below 30 cc per 24-hour period for 2 con-
secutive days. Typically this takes 1 to 2 weeks,
with the chest wall drain usually ready to
remove before the axillary drain. Drains are
removed at 4 weeks even if the output remains
high secondary to infectious risks.
Complications of Breast
Surgery
Breast surgery is relatively safe surgery, with
low rates of major complications. Wound com-
plications are typically minor and frequently
managed on an outpatient basis, but can occur
in up to 30% of cases. These include breast
infections, seromas, and hematomas. Very
rarely, more serious complications can occur.
Deep
venous
thrombosis
and
pulmonary
embolism (PE) are potential complications of
any major surgery. Pneumothorax has been
described as a result of wire localization or
inadvertently deep dissection. Brachial plexo-
pathy may occur related to a stretch injury of
a malpositioned patient.
Wound Infections
Rates of postoperative infections in breast and
axillary incisions have ranged from fewer than
1% of cases to nearly 20%. A metaanalysis on
2587 surgical breast procedures found an over-
all wound infection rate of 3.8% of cases.
Wound infections of the breast are primarily
related to skin flora, usually staphylococcal
organisms. Increased risk factors for wound
infection include obesity, tobacco use, older
age, and diabetes mellitus. Second operations
in the breast also appear to have a higher risk
of wound infection.
Whether or not lumpectomies require preop-
erative antibiotic coverage is still controversial.
Multiple retrospective and prospective studies
have yielded disparate results. Although many
retrospective series suggest a benefit of antibio-
tics, these results are slightly biased by the
Lateral
pectoral
nerve
Pectoralis
minor
Figure 12–15. Retraction of
the pectoralis major muscle,
allowing
the
interpectoral
(Rotter’s) nodes to be removed
en bloc with the specimen.
(From
Bloom
N,
Beattie
E,
Harvery
J.
Atlas
of
cancer
surgery. Philadelphia: Elsevier,
2000.)
176
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

increased use of antibiotics among higher-risk
cases. A reasonable approach, with a side
benefit of reducing costs, is to limit antibiotic
prophylaxis to high-risk patients and cases. It
is also reasonable to use preoperative antibiotics
in cases involving wire localization because this
is a foreign body, although this has not been
specifically identified as a wound infection risk
factor. Antibiotics are also recommended in
patients having a second breast operation (e.g.,
a mastectomy after an excisional biopsy or a
reexcision lumpectomy).
If an infection does occur, it usually manifests
as anincisionalcellulitis. Mild incisionalcellulitis
can be treated with oral antibiotics. However,
nonresponding or more extensive soft tissue
infections require hospitalization and intrave-
nous antibiotics. A minority of breast wound
infections progressintoafullydeveloped abscess.
These most commonly appear 1 to 2 weeks post-
operatively. Patients present with a fluctuant,
erythematous, tender mass at the surgical site.
If it is unclear whether this represents a cellulitis
or abscess, ultrasound may be helpful, although
it is often difficult to differentiate between a
consolidating seroma or hematoma and an
abscess. As with primary breast abscesses, aspi-
ration and antibiotics may avoid the need for
incision and drainage. However, postoperative
abscesses are often complex and difficult to aspi-
rate completely. Thus they usually reaccumulate.
Definitive management therefore requires inci-
sion and drainage by reopening the original
surgical wound and leaving the cavity open to
heal by secondary intention.
Seroma
Seromas are extremely common after breast
surgery secondary to the rich lymphatic drain-
age of the breast and possibly the low fibrino-
gen levels and net fibrinolytic activity within
lymphatic fluid collections. In the case of a
lumpectomy, the seroma may be desirable
because it preserves the normal breast contour,
even after a large-volume resection. This cavity
is eventually replaced by scar formation as the
cavity consolidates. In rare cases, the lumpec-
tomy seroma is quite large, causing discomfort
from a bulging fluid collection. In these cases,
simple aspiration of the excess usually is ade-
quate management.
Seroma formation under the skin flaps of
mastectomy wounds impairs the healing pro-
cess, which is why drains are usually left in
place. After 1 to 3 weeks, the skin flaps heal
and adhere to the chest wall, as evidenced by
diminished drain output. Seroma collections
that develop after drain removal can be man-
aged by percutaneous aspiration. Aspiration is
usually well tolerated because the mastectomy
and axillary incisions tend to be insensate;
these procedures can be repeated as frequently
as needed to ensure that the skin flaps are
densely adherent to the chest wall. In rare
cases when the seroma continues to recur, a
Seroma-Cath may be considered.
Hematoma/Bleeding
Bleeding complications can be diminished by
meticulous hemostasis, but even in the best
hands, they will occur. The risk is higher in
patients
using
aspirin-containing
products
and
nonsteroidal
antiinflammatory
drugs
(NSAIDs) such as ibuprofen in the preoperative
and postoperative period. These drugs have
well-known antiplatelet activity, and these
medications should be avoided for 1 to 2 weeks
before surgery (the life span of the affected pla-
telets). In addition, several over-the-counter
medications and supplements that are widely
used also have anticoagulant properties and
are recognized for contributing to bleeding
complications; these include vitamin E, gin-
seng, ginkgo biloba, and garlic.
A minority of patients may present with
excessive bruising or a small hematoma at the
site of the lumpectomy. These cases resolve
spontaneously. However, an expanding hema-
toma, either at a lumpectomy site or under-
neath the skin flaps of a mastectomy, must be
recognized as quickly as possible because sig-
nificant blood loss can occur. Postoperative
hemorrhage is often secondary to arterial per-
forators of the thoracoacromial vessels or inter-
nal mammary arteries. In some cases, these can
be managed by reestablishing the patency of
the suction catheters (which often clot when
draining blood) and applying a compression
dressing. However, in many cases the patient
should be returned to the operating room for
evacuation of the hematoma and hemostasis.
Even if a large hematoma is controlled with
pressure, it will take a long time to resolve and
may be associated with significant discomfort.
Thus in the long run, an early return to the
operating room to evacuate the hematoma
may simplify the recovery period.
Chronic Pain
Patients are often surprised that the immediate
postoperative pain is less than they expected
177
12—SURGICAL MANAGEMENT OF PRIMARY BREAST CANCER

after both a lumpectomy and mastectomy, and
that this pain usually resolves quickly. However,
a small number of breast cancer patients experi-
ence chronic incisional pain. This can be quite
debilitating, last for months to years, and not re-
solve with standard analgesics. The pain is often
described as “burning” or “constricting,” sugges-
ting a neuropathic cause, although the exact eti-
ology remains unknown. Surprisingly, it seems
to occur more commonly after lumpectomy
rather than mastectomy cases. Standard analge-
sics may not provide relief, recently successful
management has been reported with use of
serotonin uptake inhibitors, such as the antide-
pressants amitriptyline and venlafaxine.
Chronic Breast Lymphedema/
Cellulitis
It is well known that lymphedema of the upper
extremity is a common complication of axillary
surgery. Less known is that the breast can also
experience chronic lymphedema as well as
fibrosis and atrophy after breast cancer surgery.
These are often due to a combination of surgery
and radiation therapy. The European Organiza-
tion for Research and Treatment and the Radia-
tion Therapy Oncology Group have proposed
a grading system for the late effects of BCT
known as the Late Effects of Normal Tissue—
Subjective, Objective, Management, and Ana-
lytic (LENT-SOMA) scales. The LENT-SOMA
system stratifies breast symptoms on the basis
of pain magnitude as reported by the patient,
measurable differences in breast appearance,
intervention requirements for control of pain
and/or lymphedema, and presence of image-
documented
breast
sequelae
(e.g.,
photos,
mammography, CT/MRI studies).
Chronic breast lymphedema can be frustrating
for both the patient and the physician in that it is
often difficult to differentiate between lymph-
edema and cellulitis. Recurrent episodes of breast
cellulitis occurring several months to years after
lumpectomy and/or breast radiation therapy
have also been reported, although rarely. The
patients usually return with a red, swollen, and
tender breast. Although an infrequent cause,
the first step is to rule out an inflammatory recur-
rence. At a minimum this requires breast imag-
ing and possibly a skin punch biopsy. Any
abnormalities on imaging should also be biop-
sied. If everything appears benign, a standard
course of antibiotics should be initiated. Failure
to respond should prompt a change in antibio-
tics (and a skin punch biopsy if not already
done). Persistent edema and erythema may be
lymphedema and not cellulitis, and physical
therapy with a lymphedema specialist can often
help dramatically. However, for fear of spread-
ing infection, many physical therapists will not
treat until cellulitis has been ruled out. Most
cases eventually resolve, although occasionally
patients have persistent pain and inflammation,
prompting mastectomy.
Suggested Readings
1. Fisher B, Anderson S, Bryant J, et al. Twenty-year
follow-up of a randomized trial comparing total
mastectomy, lumpectomy, and lumpectomy plus
irradiation for the treatment of invasive breast can-
cer. N Engl J Med 2002;347:1233–1241.
2. Haffty BG, Harrold E, Khan AJ, et al. Outcome of
conservatively managed early-onset breast cancer
by BRCA1/2 status. Lancet 2002;359:1471.
3. Janz NK, Wren PA, Copeland LA, et al. Patient-
physician
concordance:
Preferences,
perceptions,
and factors influencing the breast cancer surgical
decision. J Clin Oncol 2004;22(15):3091–3098.
4. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralat-
eral breast cancer in BRCA1 and BRCA2 mutation
carriers. J Clin Oncol 2004;22:2328.
5. Newman LA, Kuerer HM. Advances in breast conser-
vation therapy. J Clin Oncol 2005;23(8):1685–1697.
6. Punglia RS, Morrow M, Winer EP, et al. Local therapy
and survival in breast cancer. N Engl J Med 2007;
256:2399–2405.
7. Sabel MS. Locoregional therapy of breast cancer:
Maximizing control, minimizing morbidity. Exp
Rev Anticancer Ther 2006;6(9):1281–1299.
8. Vitug AF, Newman LA. Complications in breast sur-
gery. Surg Clin N Am 2007;87:431–451.
9. Warner M, Blitt C, Butterworth J, et al. Practice advi-
sory for the prevention of perioperative peripheral
neuropathies. A report by the American Society of
Anesthesiologists’ Task Force on the prevention of
perioperative peripheral neuropathies. Anesthesiol-
ogy 2000;92:1168–1182.
178
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

13
Regional Management
of Breast Cancer
INTRODUCTION
MANAGEMENT OF THE PATIENT
WITH CLINICALLY NODE-
NEGATIVE BREAST CANCER
Noninvasive Axillary
Assessment
Axillary Ultrasound
Contraindications to Sentinel
Lymph Node Biopsy
SENTINEL LYMPH NODE BIOPSY
Surgical Technique
MANAGEMENT OF THE
CLINICALLY POSITIVE AXILLA
Axillary Lymph Node Dissection
MANAGEMENT OF THE
INTERNAL MAMMARY LYMPH
NODES
Internal Mammary Sentinel
Lymph Node Biopsy
Internal Mammary Node
Dissection
COMPLICATIONS ASSOCIATED
WITH SENTINEL LYMPH NODE
BIOPSY
Inability to Find the Sentinel
Node
Allergic Reaction to Blue Dye
Surgical Complications of Sen-
tinel Lymph Node Biopsy
COMPLICATIONS OF AXILLARY
LYMPH NODE DISSECTION
Nerve Injuries
Cording or Limited Range of
Motion
Lymphedema
Key Points
Understand the implications of regional metastases on surgical
management, adjuvant systemic therapy, and radiation therapy.
Develop an algorithm for evaluating the lymph nodes (N stage) in the
patient who is clinically node negative and clinically node positive.
Describe the technique for the performance of a sentinel lymph node biopsy,
including the options for the type and site of injection of the tracers.
Know the indications for an axillary lymph node dissection and describe
the technique.
179

Understand the pros and cons of internal mammary sentinel lymph
node biopsy and describe the technique.
Be familiar with the arguments for and against the performance of a
completion node dissection when the sentinel lymph node is positive.
Be familiar with the complications of sentinel lymph node biopsy
and axillary lymph node dissection and their management.
Describe the management of lymphedema after breast surgery.
Introduction
Ever since the lymphatic system was identified
in the 17th century, scientists have surmised
an important association between the regional
lymph nodes and the development and pro-
gression of cancers of the breast. At that time,
Rene´ Descartes proposed a lymph theory for
the origin of breast cancer in direct contrast
to the prevailing theory of the time: Galen’s
theory that cancer arose from an excess of
black bile in the body. The lymph theory of
cancer gained significant momentum in the
18th century when it was advocated by John
Hunter, the “Father of Scientific Surgery,”
suggesting that a coagulative defect in the
lymph ultimately led to the appearance of
breast cancer. Hunter called for the removal
of the cancer along with the potential areas
of lymphatic spread nearly 100 years earlier
than William Halsted.
The formal axillary lymph node dissection
(ALND) was introduced by Lorenz Heister in
the 19th century, although it was not quickly
adopted. In 1867, Charles Hewitt Moore wrote
a treatise titled, “On the Influence of Inade-
quate Operations on the Theory of Cancer,”
in which he described the importance of
removing involved axillary lymph nodes en
bloc with the cancer. He later went on to pre-
scribe full axillary dissection for all patients
with breast cancer, noting that involved nodes
may not be detected clinically. The routine use
of axillary dissection was adopted by notable
surgeons such as Ernst G. F. Ku¨ster, Richard
von Volkmann, Joseph Lister, and Samuel D.
Gross, who reported a virtual elimination of
axillary recurrences when axillary clearance
was routinely performed.
Of course, it was Halsted who most radically
changed the surgical management of breast
cancer when he first described the radical
mastectomy in 1882. This operation called
not only for the removal of the breast and
both pectoral muscles, but also, based on the
reports of the aforementioned surgeons, an
extensive
axillary
dissection
incorporating
levels I through III. Although the radical mas-
tectomy was associated with significant post-
operative deformity and diminished upper
extremity function, and the operative proce-
dure itself resulted in significant intraoperative
blood loss, it had a dramatic impact on loco-
regional control and was quickly adopted. The
modified radical mastectomy (MRM), popular-
ized by D. H. Patey in the 1930s, spared the
pectoral muscles while removing the breast and
axillary contents (levels I and II). Much less mor-
bid than the radical mastectomy, this operation
eventually replaced the radical mastectomy
when long-term followup failed to demonstrate
any breast cancer recurrences in the preserved
pectoral muscles, rarely in the level III or inter-
pectoral nodes, and no difference in survival
compared with radical mastectomy.
When it became apparent that the radical
mastectomy dramatically lowered locoregional
recurrence rates but had no significant impact
on overall survival, the relative impact that
local or regional control had on survival was
called into question. To help address these
questions, the National Surgical and Adjuvant
Breast Project (NSABP) was established by
Dr. Rudolph Noer under the supervision of the
National Cancer Institute (NCI). One of the
first trials that the NSABP conducted, NSABP
B-04, sought to specifically address the contro-
versy surrounding the ideal management of
the axillary lymph nodes (NSABP B-06 would
address the ideal local management of breast
cancer, see Chapter 12). The NSABP B-04 trial,
conducted between July 1971 and September
1974, took patients with operable invasive
breast cancers and clinically negative nodes
(n ¼ 1079) and randomized them to one of
three arms: (1) total mastectomy with ALND;
(2) total mastectomy with postoperative radi-
ation; and (3) total mastectomy with a delayed
axillary dissection only if clinically positive
axillary nodes developed. An additional 586
women with clinically positive nodes were
randomized to either radical mastectomy or
180
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

total mastectomy without axillary surgery, but
with postoperative radiation. Twenty-five-year
followup of the B-04 trial has demonstrated
no survival difference among either the node-
negative treatment groups or the node-positive
treatment groups (Table 13–1).
The NSABP B-04 trial did demonstrate the
necessity of surgical lymph node dissection in
identifying regional disease (clinical axillary
staging was incorrect in 25% to 40% of cases)
and also the superiority of surgical lymph node
dissection compared with axillary radiation for
local disease control among patients who were
clinically node positive. However, the trial also
revealed that the ALND as part of the surgical
management of breast cancer was not associated
with any survival benefit. Despite this finding,
surgical management did not change and axil-
lary dissection remained the standard of care.
There were several reasons for this. Critics of
the study point out that the study was not pow-
ered to detect a small survival benefit to ALND,
and in the mastectomy alone, many of surgeons
still included a large number of axillary nodes
with the specimen. But the strongest reason that
ALND remained standard despite no evidence of
therapeutic benefit was that the prognostic
information provided by ALND was still crucial
for adjuvant therapy decisions. So while NSABP
B-06 dramatically altered the local management
of breast cancer NSABP-04 did not, as it was still
necessary to perform routine ALND to identify
patients who were node positive. However, this,
too, would change dramatically when sentinel
lymph node (SLN) biopsy for breast cancer
emerged.
In the 80s and 90s, axillary sampling was
being investigated as a means of staging the
axilla without subjecting patients to the com-
plications of axillary clearance. During this
time,
the
use
of intraoperative
lymphatic
mapping was being investigated for other can-
cers as a method of accurately identifying the
first lymph node(s) that received drainage from
the site of a tumor. This was not a new concept.
In the mid-19th century, Virchow described the
concept of lymphatic drainage from a given
body site to a specific lymph node. Based on
studies in cats and humans with vital dye,
Braithwaite first described the “glands sentinel”
as the lymph node that drains a particular area.
In 1960, Gould described a “sentinel node” that
directly drained the parotid gland and proposed
that a radical neck dissection should be per-
formed if this node contained micrometastatic
disease. And in 1976, Cabanas suggested that
the sentinel node of the penis could be used to
determine the need for regional node dissection
for penile cancer. However, the use of intrao-
perative lymphatic mapping to identify the sen-
tinel node was truly brought forward by Donald
Morton for the treatment of malignant mela-
noma, where it was demonstrated to be highly
accurate in predicting the status of the regional
basin. In 1994, Giuliano first described the use
of SLN biopsy in breast cancer, prompting great
interest in using this technique in breast cancer
and numerous studies of SLN biopsy followed
by completion axillary lymph node dissection.
Management of the Patient
with Clinically Node-Negative
Breast Cancer
Although there are still several controversies
that exist regarding the ideal use of SLN biopsy,
it has become the standard method of iden-
tifying regional metastases in patients with
clinically node-negative breast cancer. The
ALND should no longer be considered for this
TABLE 13–1  Results of the NSABP B04 Trial
Node negative
Node positive
RM
TM
RM þ XRT
RM
TM þ XRT
Number of patients
362
365
352
292
294
OS at 25 yrs
25%
26%
19%
14%
14%
OS at 10 years
58%
54%
59%
38%
39%
OS at 5 years
75%
74%
75%
62%
58%
Of patients who were clinically node negative 19% underwent delayed axillary lymph node dissection for axillary
relapse (median time to development of positive axillary nodes 14.8 months).
Of patients who were clinically node positive randomized to TM þ XRT, 11.9% developed axillary relapse compared
to 1% in RM arm.
OS, overall survival; RM, radical mastectomy; TM, total mastectomy; TM þ XRT, total mastectomy and external
beam radiation.)
181
13—REGIONAL MANAGEMENT OF BREAST CANCER

purpose, except in cases in which SLN biopsy is
not possible. Outside of this scenario, the ALND
should be thought of as a therapeutic procedure
for patients with documented lymph node
involvement. However, before proceeding with
surgical management, a thorough evaluation
should be completed to identify patients with
regional involvement so that these patients
may be spared SLN biopsy and proceed directly
to axillary clearance (Fig. 13–1).
Noninvasive Axillary Assessment
If it has not already been done as part of the ini-
tial evaluation, any patient diagnosed with
breast cancer requires a detailed examination
of the regional lymph nodes, including the
axilla, supraclavicular, and cervical basins. With
the patient sitting up, the examination should
begin with the cervical lymph nodes along the
anterior border of the sternocleidomastoid
muscle. As the examiner moves downward, ade-
nopathy should be sought in the supraclavi-
cular fossa and possibly some infraclavicular
nodes within the deltopectoral groove. To
examine the axillary nodes, the examiner
should face the patient or stand slightly to his
or her side. The examiner uses the nonpalpat-
ing hand to either steady the patient’s shoulder
or support his or her arm, asking him or her to
let it go loose to relax the pectoralis major and
axillary fascia (Fig. 13–2). Examining the axilla
without relaxation of the fascia will severely
limit the ability to detect palpable adenopathy.
Physical examination of the axilla involves
palpation of the anterior, deep, and posterior
axillary surfaces. Enlarged or firm nodes may
sometimes be detected on firm compression of
the axillary tissues against the smoother surface
of the pectoral muscles, the lateral chest wall, or
the subscapular musculature. The examination
should start high in the axilla. In this way, the
axillary nodes are trapped lower rather than
initially pushed upward. Gently palpate back
and forth to feel if any nodes are apparent. Sev-
eral passes should be made from top to bottom,
both anteriorly and posteriorly in the axilla. If
any lymph nodes are detected, their size, consis-
tency, and fixation should be noted.
It is important to acknowledge that physical
examination alone is highly inaccurate for clin-
ical staging, lacking in both sensitivity and
specificity. Obviously micrometastatic disease
will not be identified on physical examination.
However, it is also possible to have a false-
positive finding. Normal lymph nodes can
sometimes be palpated depending on the body
habitus of the patient, and sometimes enlarged
lymph nodes are present in response to a previ-
ous breast biopsy. As many as 40% of clinically
positive examinations may be inaccurate, even
in experienced hands. Given that today women
who are node negative can be spared the mor-
bidity of ALND, the impact of a false-positive
Patient with documented
invasive breast cancer
Clinically
suspicious nodes
Clinically
node negative
History and physical
FNA Biopsy
Axillary ultrasound
with FNA biopsy of
suspicious nodes
FNA
positive
FNA
negative
ALND
SLNBx
FNA
negative
FNA
positive
ALND
1° tumor <1.0 cm
1° tumor >1.0 cm
Figure 13–1. Clinical staging
of the axilla. Patients with palpa-
ble axillary lymph nodes should
undergo fine-needle aspiration
(FNA) biopsy to confirm meta-
stases. Because palpable nodes
are
not
always
involved
by
cancer, a negative FNA should
prompt a sentinel lymph node
(SLN)biopsy, takingcare toexcise
any suspicious nodes regardless
of whether they take up the
tracer. For patients who are clini-
cally node negative, axillary ultra-
sound
and
ultrasound-guided
FNA biopsy will identify many
patients who have regional meta-
stases, allowing them to proceed
to axillary lymph node dissection
(ALND) or neoadjuvant chemo-
therapy. The size cutoff for the
routine use of axillary ultrasound
varies
among
institutions.
At
the University of Michigan, all
patients with an invasive cancer
greater than 1 cm undergo rou-
tine axillary ultrasound.
182
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

physical examination can be significant. There-
fore, fine-needle aspiration (FNA) biopsy should
be used to confirm the presence of metastatic
disease in any patient with breast cancer with
palpable axillary lymph nodes. This can be
done freehand or with ultrasound guidance.
If FNA confirms the presence of metastatic
disease, then when the patient proceeds to
lumpectomy or mastectomy, a level I and II
ALND should be performed. If the FNA is nega-
tive, however, ALND should not be the next
step. If the examiner is highly suspicious of
lymph node involvement and believes the
negative FNA is secondary to sampling error,
it may be worth performing an ultrasound-
guided biopsy. In other cases, surgical lymph
node excisional biopsy can be performed if
the presence or absence of lymph node metas-
tasis is a key component of the therapeutic
algorithm.
If the examiner is confident that the node
was sampled correctly, or the image-guided
biopsy is also negative, the patient should
undergo SLN biopsy at the time of their lump-
ectomy or mastectomy. It is crucial that the
surgeon also remove the palpable node at the
time of SLN biopsy, even if it does not demon-
strate uptake of either the radioactive tracer or
blue dye and consider frozen section analysis
or imprint cytology to evaluate for metastases.
Axillary Ultrasound
In the patient with documented breast cancer
and no palpable adenopathy, imaging of the
axilla with ultrasound
is rapidly becoming
standard practice for preoperative axillary assess-
ment. Sensitivity of axillary ultrasound in identi-
fying abnormal nodes ranges from 50% to 70%;
specificity is between 85% and 95%. When axil-
lary FNA biopsy of abnormal lymph nodes is
added to axillary ultrasound, the sensitivity
increases to nearly100%insomestudies.The pre-
operative diagnosis of axillary metastasis is
extremely helpful in the staging and operative
planning of the patient with breast cancer. As
SLN biopsy is not an inexpensive procedure,
sparing patients with known lymph node meta-
stases from the procedure not only simplifies
their treatment but also saves health care dollars.
It is also helpful in the preoperative staging and
patient selection of patients considered for
neoadjuvant chemotherapy. Several institutions
consider it common practice to routinely obtain
axillary ultrasounds on all patients with invasive
cancers greater than 1.0 cm.
There are several criteria by which a lymph
node is deemed suspicious on ultrasonography
(Table 13–2). Abnormal lymph nodes are iden-
tified by either their size or a change in their
general appearance on ultrasound (Figs. 13–3,
13–4, 13–5). Size is felt to be the weakest pre-
dictor of abnormality; normal nodes generally
measure between 4 and 6 mm in length, and
although nodes greater than 10 mm in length
are generally considered abnormal, changes
in morphology are significantly more useful
in diagnosing metastasis. Rounding of the nor-
mal elliptical shape is considered an indication
of neoplastic infiltration. Obliteration of the
normally hypoechoic nodal cortex, irregulari-
ties of the cortical or medullary contours, and
A
B
Figure 13–2. A, B: Axillary examination. The examiner should face the patient or stand slightly to his or her
side. The examiner uses the nonpalpating hand to either steady the patient’s shoulder or support his or her
arm, asking him or her to let it go loose to relax the pectoralis major and axillary fascia. (From Roses D. Breast
Cancer. Philadelphia: Elsevier, 2005.)
183
13—REGIONAL MANAGEMENT OF BREAST CANCER

eccentric
compression
of
the
hyperechoic
nodal medulla are also suggestive of metastatic
disease. Loss of the nodal capsule is also an
indicator of tumor invasion. The addition of
color-flow Doppler may also enhance the diag-
nostic sensitivity of axillary ultrasound; hy-
pervascularity and visualization of multiple
feeding vessels for a single lymph node are
strong indicators of neoplastic activity. Any
abnormal lymph nodes identified on axillary
ultrasound should undergo ultrasound-guided
FNA to confirm the presence of metastases.
Patients
with
FNA-proven
regional
disease
can be spared the time and expense of SLN
biopsy and proceed directly to ALND at the
time of their lumpectomy or mastectomy.
Contraindications to Sentinel
Lymph Node Biopsy
Patients with invasive cancer and no clinical
evidence of axillary disease are candidates for
SLN biopsy. As stated, patients with palpable
axillary nodes or suspicious lymph nodes on
axillary ultrasound should be initially evaluated
by FNA, with or without ultrasound guidance
(Box 13–1 and Box 13–2).
Besides the patient who is clinically node pos-
itive, are there other indications when SLN
biopsy is contraindicated? When SLN was first
introduced clinically, its use was limited to
small, unicentric invasive cancers. However,
the success rates and accuracy of the procedure
have subsequently been described in patient
populations in which SLN biopsy was consid-
ered contraindicated. These include patients
with multicentric cancers, patients with large
Figure 13–3. Axillary lymph node with symmetric
cortical thickening. (Image courtesy of Dr. Alexis
Nees,
Department
of
Radiology,
University
of
Michigan.)
Figure 13–4. Axillary lymph node demonstrates
asymmetric cortical thickening with flattening and
compression
of
the
hilum.
(Image
courtesy
of
Dr. Alexis Nees, Department of Radiology, University
of Michigan.)
TABLE 13–2  Features of a Suspicious
Lymph Node on Ultrasound
 Increased size
 Abnormal node adjacent to normal node (less
likely to be inflammation)
 Rounded shape as opposed to normal ovoid
shape
 Hypoechoic cortex
 Loss of echogenic outer capsule and angular
margins
 Cortical thickening: uniform versus eccentric
 Hilar compression: uniform versus eccentric
 Hilar indentation (“rat bite”)
 Hilar displacement or obliteration
 Hypervascular flow patterns
184
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

(>5 cm) primary tumors, and even patients with
previous axillary surgery or breast irradiation.
Many of these changes were prompted by altera-
tions in the method of injection of the tracer. For
example, tumor size had been considered a pos-
sible contraindication to SLN biopsy. Most sur-
geons recommend SLN biopsy for patients with
clinically node-negative breast cancers with T1
and T2 tumors (less than 5 cm). However, SLN
biopsy has been shown to be accurate for
patients with larger tumors. On one hand, most
of these patients (as high as 75%) will have
regional metastases, so most will inevitably pro-
ceed to complete node dissection. On the other
hand, even if it is a minority of patients, it is
worth sparing these patients from the morbidity
of an ALND. These patients are obviously ideal
candidates for preoperative axillary ultrasound
with ultrasound-guided FNA biopsy of any
abnormal lymph nodes. If negative, a subset of
these patients will still benefit from SLN biopsy.
Many women with T3 tumors will be candidates
for neoadjuvant chemotherapy. How the senti-
nel node procedure should be incorporated with
neoadjuvant chemotherapy is discussed in detail
in Chapter 18. In any such case, however, it falls
on the judgment of the surgeon as to whether
SLN biopsy will give an accurate representation
BOX 13–1 ABSOLUTE
CONTRAINDICATIONS TO SENTINEL
LYMPH NODE BIOPSY
Clinically involved lymph nodes
(confirm by fine-needle aspiration)
Inflammatory breast cancer
Figure 13–5. Lymph node on right demonstrates
round shape with compression of the fatty hilum.
Lymph node on left demonstrates loss of fatty hi-
lum. Ultrasound-guided fine-needle aspiration (FNA)
confirmed metastatic disease. (Image courtesy of
Dr. Alexis Nees, Department of Radiology, University
of Michigan.)
BOX 13–2 CONTROVERSIES IN THE
USE OF SENTINEL LYMPH NODE
BIOPSY
Prophylactic
mastectomy
Pro: Staging of axilla
if incidental cancer is
detected.
Con: Low likelihood of
incidental cancer does not
justify the cost of the
procedure.
Ductal
carcinoma in
situ
Pro: Staging of axilla if
incidental invasive cancer
is detected after
mastectomy.
Con: If invasion is
detected after
lumpectomy, a sentinel
lymph node (SLN) biopsy
can still be performed.
Multicentric
breast cancer
Con: Accuracy of SLN
biopsy is not verified for
multicentric cancer.
Pro: Studies of periareolar
injection suggest a
common drainage pattern
for all quadrants.
Pregnancy
Blue dye is
contraindicated because
of an allergic reaction.
Methylene blue has not
been studied.
Tc99 appears safe,
although some surgeons
are hesitant to use it.
Previous
axillary
surgery
Con: Disruption to
lymphatic pathways
makes the accuracy of the
procedure questionable.
Pro: Several studies have
demonstrated feasibility
of the approach.
185
13—REGIONAL MANAGEMENT OF BREAST CANCER

of the nodal status. If there is reasonable con-
cern, either before or during the procedure, then
ALND should be performed.
Another area of controversy is the use of
SLN with noninvasive breast cancer. Although
SLN biopsy is primarily indicated in patients
with invasive breast cancer, there are some
situations in which it may be considered in
patients with ductal carcinoma in situ (DCIS;
see Chapter 11). Patients undergoing mastec-
tomy for DCIS are candidates for SLN biopsy.
This is primarily done as a method to stage
the axilla should an unexpected invasive com-
ponent be identified within the mastectomy
specimen. If invasive cancer is incidentally iden-
tified in a patient with DCIS undergoing a sim-
ple mastectomy without SLN biopsy, the only
option for staging the axilla is a complete ALND.
Patients undergoing lumpectomy for DCIS do
not require SLN biopsy; if an invasive com-
ponent is discovered, they may return to the
operating room. It is not unreasonable, however,
to consider SLN biopsy in patients with DCIS
undergoing breast conservation for whom there
is a strong clinical suspicion for an invasive
component, such as patients with DCIS present-
ing as a palpable mass or those with extensive
high-grade DCIS with comedonecrosis.
Sentinel Lymph Node Biopsy
Surgical Technique
Injection of Tracers and Patient
Preparation
Sentinel node biopsy is a multistep procedure,
involving perioperative localization followed
by intraoperative nodal excision. The method
of nodal localization has been a subject of
much investigation, using different timing
sequences, agents, and injection techniques
to determine the optimum procedure for iden-
tifying the sentinel node.
The initial description of the sentinel node
procedure used blue dye only as a method of
localizing the SLN. Today, the most common
approach to SLN biopsy is the use of a combi-
nation of tracers, which had most commonly
consisted of technetium 99-m (Tc99) and Lym-
phazurin (isosulfan blue dye). With recent dif-
ficulties
in
obtaining
Lymphazurin,
many
surgeons have shifted to the use of Methylene
blue dye. The application of both a nuclear
tracer and blue dye does increase the sensitiv-
ity, specificity, and accuracy of sentinel node
identification. However, use of blue dye alone
has a sentinel node identification rate ranging
from 77% to 92%, making sentinel node
biopsy feasible in facilities that lack nuclear
medicine capabilities.
The timing and technique of the injection of
these tracers for sentinel node localization has
been extensively researched. The procedure
typically begins with the injection of the Tc99;
a radiotracer bound to a colloid substance that
travels through the lymphatic system. Sulfur
colloid is the molecule commonly used in the
UnitedStates;albuminis oftenthe preferredcom-
pound overseas. In the United States, Tc-99m
sulfur colloid is available as unfiltered or fil-
tered, having been passed through a 22-mm
filter. The uptake and travel time depend on
the size of the labeled carrier and the amount
of carrier fluid used. Larger particles may never
make it to the nodes, whereas small particles
may go too quickly, possibly resulting in multi-
ple positive nodes. Filtration eliminates much
of the heterogeneity found in the sulfur colloid
molecules, theoretically producing a more con-
centrated and easily localized radioactive signal
when explored with a gamma probe. Filtration
through 100- or 220-nm filters has been stud-
ied, with goals of particle sizes ranging from
50 to 200 nm. A number of studies have been
performed, examining the clinical benefit of
using filtered versus unfiltered Tc-99m. The
results have failed to demonstrate a clear
advantage of one over the other. Selection
may depend on the relative advantages and dis-
advantages, including when the injection is
performed (day of versus night before).
Often the injections are performed the morn-
ing of the surgery, with lymphoscintigraphy
performed 2 hours after injection. This can
complicate surgical scheduling because cases
involving SLN biopsies cannot begin until late
morning. Several studies have demonstrated
no difference in node identification rates using
Tc-99m between 2 and 24 hours after injection,
a fact that often simplifies the logistics of sche-
duling surgery by allowing the injection to take
place the night before.
The technique of injection for sentinel node
localization has also been examined by several
institutions for both the radioactive colloid and
the blue dye. Originally, injections were always
performed peritumorally based on the concept
that this would be the most accurate anatomi-
cally. The peritumoral injection involves injec-
tion of the tracer in the breast parenchyma
surrounding the tumor or the cavity from the
excisional biopsy. However, this requires that
the person injecting the tracer (often a nuclear
186
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

medicine technician) knows where the tumor is,
which for nonpalpable lesions can be an issue. In
addition, accidental injection into the cavity
results in a failure of localization. Subsequent
studies have shown that other methods of injec-
tion are equally accurate, if not more so. Periar-
eolar, subareolar, and intradermal injections
have all been used in various studies with both
blue dye and radioactive colloid (Table 13–3).
Intradermal injections still require knowledge
of the tumor location, and unless the skin over-
lying the tumor is resected, will leave residual
radiation and blue dye. For tumors in the upper
outer quadrant, false gamma countersignals, col-
loquially referred to as “shine through” from a
peritumoral or intradermal Tc99 injection can
make identification of the SLN difficult. Many
surgeons advocate periareolar or subareolar
injections for the radioactive colloid. This sim-
plifies the procedure because the person inject-
ing the tracer does not need to know where in
the breast the tumor is. This also avoids the shine
through phenomenon for upper outer quadrant
tumors.
Lymphoscintigraphy
The use of routine lymphoscintigraphy is con-
troversial in breast cancer lymphatic mapping
(Fig. 13–6). If the surgeon is prepared to go
after internal mammary lymph nodes should
they take up the tracer, then lymphoscintigra-
phy is essential. The tracer should also be
injected
peritumorally
because
intradermal
and periareolar injections rarely demonstrate
TABLE 13–3  Relative Advantages of Different Injection Techniques
Pros
Cons
Intraparenchymal
(peritumoral)
Conceptually the “purest” mapping route in
replicating intramammary lymphatic path from
breast tumor to sentinel node(s)
More likely to map to internal mammary lymph
nodes (IMNs)
Difficult for nonpalpable tumors
Risk of injecting into breast cavity
Where to inject for multiple tumors
Shine-through effect for Tc99 for
upper outer quadrant tumors
Dermal
Rapid lymphatic uptake
Easier with nonpalpable tumors, but requires
marking of skin overlying lesion less shine
through
Where to inject for multiple tumors
May require image-guided
marking of skin site overlying
nonpalpable tumor
Blue tattooing of skin
Risk of necrosis with methylene
blue dye
Less identification of internal
mammary nodes
Subareolar or
periareolar
Rapid lymphatic uptake
Less shine through
Can be used for cases of multiple breast tumors
Does not require knowledge of tumor location
Possibly more physiologic, based on embryologic
lymphatic system development
“Blue breast” syndrome
Risk of necrosis with methylene
blue dye
Less identification of IMNs
INJ
A
B
INJ
Figure 13–6. A, B: Lymphoscintigrams showing uptake in ipsilateral axillary lymph nodes after periareolar
injection of Tc99.
187
13—REGIONAL MANAGEMENT OF BREAST CANCER

internal mammary lymph nodes. Otherwise,
the lymphoscintigraphy does not appear to
be necessary or helpful in identifying the sen-
tinel node. Cost and reimbursement issues,
however, dictate that if nuclear medicine is
going to be doing the injection of the radioac-
tive colloid, then they must also perform lym-
phoscintigraphy. If lymphoscintigraphy is to
be eliminated, then in most cases the surgeon
will have to assume the responsibility for the
storage and disposal of the radioactive sub-
stances and waste.
Sentinel Lymphadenectomy
Once the patient is in the operating room, injec-
tion of the blue dye takes place. Although many
surgeons use isosulfan blue dye for this, the
recent difficulties in obtaining Lymphazurin
have led to many surgeons to use methylene
blue instead, and in many cases liking it better
than Lymphazurin, citing lower cost, fewer aller-
gic reactions, and similar efficacy. If isosulfan
blue dye is used, allergic reaction is an important
complication of the procedure for the surgeon to
keep in mind during this portion of the proce-
dure and to discuss preoperatively with the
patient. Allergic reactions can occur in 1% to
2% of patients. Most of these involve urticaria,
blue hives, or pruritus, however about 0.5%
may have bronchospasm and hypotension. If
the patient is undergoing general anesthesia, it
is reasonable to delay the injection of the blue
dye until the airway is secured. Allergic reaction
should be considered in any patient experien-
cing hypotension in which blue dye was used
and is readily managed with fluid resuscitation
and short-term pressor support.
Methylene blue does not carry the same risk of
allergic reaction, however, it does carry the risk
of skin necrosis. For this reason, it should be
diluted with normal saline. The recommended
dilution is 2 ml of methylene blue dye and 3 ml
of normal saline. It is also advisable to not per-
form an intradermal injection of the methylene
blue dye, using peritumoral injections only.
The method of injection for the blue dye
can be peritumoral, intradermal, or subareolar.
Multiple studies suggest the superiority of
intradermal injection compared to subdermal
or deeper peritumoral breast injections. Injec-
tion of the dermal lymphatics is felt to drain
the marker faster to the axilla than injection
into the breast parenchyma. However, intra-
dermal or subareolar injections of blue dye
may cause tattooing of the nipple or skin,
which may persist for months in patients
undergoing breast conservation. In the case
of methylene blue dye, skin necrosis is a signif-
icant complication as well. In a patient under-
going a mastectomy, either an intradermal or
subareolar injection of the blue dye seems
ideal. For the patient undergoing lumpectomy,
intradermal injection can be used if the over-
lying skin will be resected with the tumor.
Otherwise a peritumoral injection of the blue
dye will provide adequate localization without
leaving the breast tattooed for an extended
period of time. Care must be taken to avoid
injecting the blue dye into a cavity after an
excisional biopsy. After injection, the breast is
gently massaged for approximately 5 minutes.
Nodal excision is typically performed via a
small axillary incision, posterior to the lateral
border of the pectoral muscle. Preoperative
scanning with the gamma probe is often help-
ful in planning the incision. The incision
should be easily incorporated into an incision
for a subsequent ALND (Fig. 13–7). Nodes that
stained blue or with attached blue lymphatic
Point of
maximum
radioactivity
Biopsy site
Figure 13–7. The gamma probe is used to identify the point of maximum counts. A small incision should be made
here, being sure it can be easily incorporated into an incision for a subsequent axillary lymph node dissection.
188
SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY

channels, or with evidence of radioactivity on
the gamma probe, are excised intact and sent
in formalin for pathologic review (Fig. 13–8).
In addition, nodes that are palpably firm or
enlarged should also be excised. The procedure
is considered complete after scanning with the
gamma probe fails to reveal further radioactive
counts greater than 10% of the highest count
detected.
In some cases the lymphoscintigraphy will
demonstrate uptake in the internal mammary
lymph nodes (IMNs; Fig. 13–9). The routine
biopsy of these nodes has become a point of
much contention. Between 5% and 10% of
patients undergoing lymphoscintigraphy will
have evidence of radioactivity at the ipsilateral
IMN chain. This is partly dependent on the
method of injection. Internal mammary drain-
age is more commonly seen after peritumoral
injection and much less so after subareolar or
intradermal injection. In patients who drain
only to the IMN, or to both the IMN and axil-
lary nodes, the surgeon should consider each
patient individually, considering the possible
impact on subsequent therapy decisions should
IMN metastases be identified (Box 13–3). A fur-
ther discussion of the IMNs is presented later in
this chapter.
Intraoperative Evaluation of the
Sentinel Lymph Node Biopsy
Intraoperative evaluation of sentinel nodes
has been investigated in a number of studies,
in hopes of sparing patients from multiple
operations for axillary staging and clearance.
Frozen section analysis of SLNs has proved to
be accurate for identifying macrometastatic
lesions, however, this adds considerable time
Figure 13–8. In vivo image of a sentinel lymph
node taking up blue dye. A node is considered a sen-
tinel lymph node if it is blue, partially blue, or has a
blue stained lymphatic leading to it. (Image courtesy
of Dr. Tara Breslin, Department of Surgery, Univer-
sity of Michigan.)
INJ
Figure 13–9. Lymphoscintigraphy showing uptake
in the internal mammary nodes.
BOX 13–3 ARGUMENTS FOR AND
AGAINST ROUTINE EXPLORATION
AND BIOPSY OF INTERNAL
MAMMARY LYMPH NODE UPTAKE
ON LYMPHOSCINTIGRAPHY
For:

The presence of metastases in the
internal mammary lymph node (IMN)
provides critical staging information
and may impact adjuvant therapy.

Possibly more prognostic than axillary
nodes.

Preventing IMN recurrence is crucial
as this can be difficult to manage
clinically.
Against:

Technically challenging, risk of
pneumothorax.

Many patients with IMN uptake on
lymphoscintigram will not have
identifiable sentinel lymph node (SLN)
at surgery.

Few patients with IMN uptake have
tumor involvement (0% to 6%) and many
also have axillary involvement, hence
impact on adjuvant therapy decisions is
negligible.
189
13—REGIONAL MANAGEMENT OF BREAST CANCER