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140 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
Bone marrow micrometastases can be detected
through the use of monoclonal antibodies
against cytokeratins found specifically on epithelial cells. The detection of micrometastases
in the bone marrow of breast cancer patients
may help predict prognosis and guide adjuvant therapies. Approximately 2 mL of marrow
is drawn from each anterosuperior iliac crest
and then studied using an anticytokeratin
monoclonal antibody immunocytochemical
technique, PCR, or flow cytometry. The relatively simple procedure can be done at the
time of surgical resection with intravenous
sedation and local anesthesia. Numerous studies have shown that bone marrow micrometastases not only correlate with the size and grade
of the primary tumor, but also with distant
recurrence and survival, and can stratify
patients with similar TNM staging. More
importantly, bone marrow micrometastases
may be present in patients with negative SLN
nodes, identifying a subset of patients with
unrecognized micrometastases. Risk can be
further stratified by the quantity of breast cancer cells in the marrow.
Ongoing prospective studies will further
quantify the risk associated with the presence
of bone marrow micrometastases, but there
are, at present, no data on the outcome of
bone marrow micrometastases–negative patients
who avoid chemotherapy. Therefore, while
the finding of bone marrow micrometastases
may argue for the addition of systemic therapy in the patient who was otherwise not a
strong candidate (node-negative, small primary tumor), the absence of bone marrow
micrometastases cannot be used to withhold
chemotherapy from an otherwise reasonable
candidate. It is also not clear how much bone
marrow micrometastases adds in the era of
Oncotype DX and genetic analysis of the primary tumor (see Chapter 16). For now, bone
marrow aspiration should only be performed
as part of an investigational trial.
Markers of tumor cell proliferation have
also been examined for their prognostic and
predictive value. S-phase fraction, DNA ploidy,
and an elevated thymi dine labeling index (TLI)
are signs of increased proliferation and have
been correlated with tumor size, grade, and
stage. Positive IHC staining for Ki-67 (a cell-
cycle–specific nuclear antigen present only
in proliferating cells) has also been correlated
with advanced grade and stage and worse outcome. However, none of these tests has been
shown to impact management of the breast
cancer patient and their routine use is not
recommended.
Genetic Counseling
As stated, there is information that, although
not considered “standard” staging information, greatly impacts the workup, treatment,
and surveillance of the breast cancer patients.
One example of this is the family history of
the patient and the implications regarding
their risk of a second breast cancer. It has
been known for some time that families with
a disproportionate amount of breast and/or
ovarian cancer exist. Careful analysis of these
families suggested that the malignancy was
transmitted as an autosomal dominant trait.
This ultimately led to the discovery of mutations in the genes BRCA1 and BRCA2. It is
estimated that these genes account for approximately 5% and 10%, respectively, of all breast
and ovarian cancer. Chapter 8 discusses the
risk of cancer among BRCA carriers in more
detail. However, patients with breast cancer,
especially young patients, must be concerned
with their risk of developing a second cancer.
Thus a discussion of that risk and options to
minimize it, including surgical, must be part
of the preoperative assessment.
The question will arise as to whether to pursue genetic testing before proceeding with surgery. The ultimate question is whether this
patient would benefit from bilateral mastectomy, not only to treat the known cancer but
also to prevent the development of a second
breast cancer. However, obtaining genetic testing is not as simple a decision as that of
obtaining a staging chest x-ray study or CT
scan. There are implications not only for the
patient but also the patient’s family. Interpreting the results is not always straightforward.
Most importantly, genetic testing may not
impact surgical decision making. Patients with
a strong family history of breast cancer may
have decided to proceed with bilateral mastectomy regardless of their BRCA results. In contrast, candidates for breast conservation may
not be willing to undergo prophylactic mastectomies regardless of risk. The benefit of prophylaxis must also be weighed against the
risk of recurrence and death resulting from
the primary tumor. Thus genetic testing
should almost never be ordered by the surgeon, but rather by a genetic counselor after
an adequate assessment of the likelihood of
14110—WORKUP AND STAGING OF THE BREAST CANCER PATIENT
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
harboring disease and discussion of the interpretation and potential benefits of testing.
Who should be referred to a genetic counselor? 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 mayhelp 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 predisposition to breast or ovarian cancer, based on a thorough 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 history that includes soft tissue sarcomas, osteosarcomas, brain tumors, or leukemias. Histories
that include breast cancer, benign breast disease,
thyroid, renal, and endometrial cancer may suggest Cowden syndrome (PTEN).
Presentation at a Multidisciplinary Tumor Board
Finally , before proceeding with treatment, it is
prudent topresent patient cases ata breastcancer
multidisciplinary tumor board (Box 10–4). The
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
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 appropriate 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
patienthad x-raystudies or biopsiesat an outside
institution because it allows for a second and
potentially an expert review of the findings. In
many cases, this review may change the recommended surgery. Review of the mammogram
may reveal a second area of suspicion that
requires biopsy before proceeding with lumpectomy or calcifications that preclude breast conservation. Review of the pathology may change
the margin status, affecting the need for reexcision, or it may find or question the presence of
an invasive component in predominantly insitu
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 surgeon review the history, physical, and imaging
findings together before deciding upon breast
conservation. Concerns of the radiation oncologist, based on comorbidities, underlying
medical conditions, body habitus, or mammographic 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
142 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
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 multidisciplinary tumor board is the dialogue
between the medical oncologist and surgeon
on the use of neoadjuvant chemotherapy. Chemotherapy 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 downstaged, 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 radiation 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 process. 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 appropriate for open research protocols.
Patients are often concerned that the time it
takes to get a second opinion from a multidisciplinary team may be detrimental. They feel that
the cancer needs tobe removed as soon as possible 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 without 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 http://www.nccn.org/professionals/physician_gls/
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.
11
Management of Ductal Carcinoma In Situ and Paget Disease
INCIDENCE
NATURAL HISTORY
CLASSIFICATION
PRESENTATION
TREATMENT
Mastectomy
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.
Breast Conservation Therapy
Lumpectomy Alone for DCIS
Management of the Axilla
Hormonal Therapy
PAGET DISEASE
Clinical Presentation
Treatment
Ductal carcinoma in situ (DCIS) is a noninvasive 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 invasive ductal carcinomas appear to originate
143
144 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
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 mediumsized 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 pathologic features, diverse malignant potential,
and multiple treatment options. The treatment 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 mammography. Before this, DCIS was a very different disease entity, often presenting as either a
palpable mass, nipple discharge, or Paget disease (see later). It represented only a small fraction of breast cancer cases (approximately 1%
to 3%). Unsure exactly how to treat it, recommendations ranged from simple observation
to modified radical mastectomy. Between 1983
and 1992, as screening mammography became
widespread, incidence rates increased dramatically. 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 preinvasive form of breast cancer dates back to
1906, th e 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 longitudinal 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 potential, 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.
TABLE 11–1Traditional Architectural Classification for DCIS
Architectural
Pattern
Micropapillary Intraluminal projection of cells, club shaped, lack
Papillary Intraluminal projection of tumor cells,
Cribriform Small cells, small hypochromatic nuclei, back-to-back
Solid Not as well defined, tumor cells fill and distend
Comedo Large cells, nuclear pleomorphism, mitotic activity,
Cytologic
Features
fibrovascular
fibrovascular cores
glands
involved space
often associated with microinvasion
Historically DCIS has been classified into
five subtypes (postulated to represent steps in
evolution and worsening malignant potential)
based on architectural pattern: micropapillary, papillary, cribriform, solid, and comedo
(Table 11–1)(Figs. 11–1 through 11–3). More
recently the emphasis has been on the presence of necrosis and nuclear grade (Fig. 11–4).
This is based on the fact that these factors have
the most significant association with microinvasive disease and the propensity for recurrence. DCIS is not associated with a high risk
of regional or distant recurrence, so the focus
centers on local control, particularly on preventing an invasive recurrence. This is particularly true as more women opt for breast
conservation. Hence the current recommendation is for each histopathologic report to individually comment upon morphology, nuclear
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.)
Calcifications Cell
Minimal, small Limited to
Minimal, small Variable
Minimal, small Limited to
Variable Not
Linear,
branching
Necrosis
single cells
single cells
significant
Prominent
14511—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE
Figure 11–1. Micropapillary growth pattern of duc-
tal carcinomain situ. A proliferation of neoplastic cells
replace the epithelium lining and form small projections. These can coalesce, forming curvilineous
structures. (Image courtesy of Maria Braman, MD,
Department of Pathology, University of Michigan.)
Figure 11–3. Solid growth pattern of ductal carcinoma in situ. The cells completely fill the duct without necrosis. (Image courtesy of Maria Braman, MD,
Department of Pathology, University of Michigan.)
146 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
untreated due to missed diagnoses provide
valuable insights; there is convincing evidence
that most DCIS would proceed to invasive cancer. After 30 years of follow-up, approximately
two thirds of these patients progressed to invasive 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 invasive ductal carcinoma is additional proof.
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.)
However, better definition of the molecular
factors required for DCIS to progress to invasive disease is needed to better differentiate
between the cases of DCIS that could in the
grade, and necrosis. Several systems exist for
classifying DCIS by these features (Table 11–2).
future be safely observed versus those cases
that may need treatment.
ginates from a single site with longitudinal
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 important to keep in mind, however, that the progression from cellular proliferation, to atypical
hyperplasia, to noninvasive cancer, and ultimately to invasive cancer has been hypothesized 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 surgery 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.
extension along the ductal systems. Crosssectional proliferation and progression to invasion occurs concurrently, so the larger the area
of DCIS, the morelikely it isthat there are microinvasive foci. There is a much higher prevalence
of invasive disease in cases of diffuse DCIS.
present, DCIS does not invade through the basement membrane and therefore cannot spread to
the regional lymph nodes or distally. Review of
modified radical mastectomy specimens performed 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 possibility of an inherently aggressive form of DCIS
cannot be ruled out.
Past studies of patients with DCIS left
Studiessuggest thatDCIS mostcommonly ori-
By definition, unless microinvasive disease is
TABLE 11–2Histopathologic
Classifications for DCIS
European Van Nuys Lagios
Well differentiated Non–high
Moderately
differentiated
Poorly
differentiated
grade
No necrosis
Non–high
grade with
necrosis
High grade High grade
Low grade
Intermediate
grade
Classification
Although DCIS has classically been classified
by morphology, for clinical purposes, many
authors have simply characterized DCIS as comedo 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 cancer 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
14711—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE
variationinlabelingDCISascomedoornoncomedo. Two other important pathologic features
arenucleargradeandthepresenceofnecrosis.
Silverstein and colleagues have proposed dividing 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 development of invasive breast cancer.
Presentation
Although today most patients present with an
abnormality onroutine screening mammogram,
approximately 9% of patients still present with
a palpable mass, nipple discharge, or as Paget
diseaseof 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 diagnosed 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 common 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
Figure 11–5. Paget disease of the nipple. The nipple
areolar complex is scaly and eczematous. (Image
courtesy of Celina Kleer, MD, Department of Pathology, University of Michigan.)
and features of associated mammographic calcifications. The most characteristic feature of
comedo DCIS is casting-type calcifications—
linear branching patterns depicting alignment
in a ductal distribution. Conversely noncomedo 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 calcifications, 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, including ultrasonography, magnetic resonance imaging, 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. Calcifications may be detected by a high frequency
probe in up to 60% of lesions, usually the comedo subtype. Ultrasound’s sensitivity is estimated 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 evolving, 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 various available options include fine-needle aspiration (FNA), percutaneous core-needle biopsy
under stereotactic, sonographic, or tactile guidance (when palpable), and surgical biopsy with
or without wire localization. The absolute sensitivity 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 microcalcifications with surgical excision is used for
148 SURGICAL FOUNDATIONS: ESSENTIALS OF BREAST SURGERY
A
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, Department of Radiology, University of Michigan.)
diagnosis if the aforementioned procedures cannot be performed due to technical or patientrelated factors, a situation that is becoming
increasingly rare.
It is important to remember that image-guided
core biopsy techniques may understage malignant microcalcifications. Studies indicate that
approximately 10% to 15% of 14-gauge core
biopsy specimens revealing atypical ductal hyperplasia (ADH), a benign condition, get histopathologically 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 localization excision to rule out any residual DCIS or
invasive cancer.
B
Today, a variety of treatment options, ranging
from excision alone (lumpectomy or breastconserving therapy) to mastectomy, with or
without radiation therapy (XRT), have been
proposed for DCIS. When treating invasive
breast cancer, local control efforts may be tempered 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,
Treatment
occult invasive cancer coexisting with the in
situ lesion, and multicentricity are important
With the evolution of our knowledge of the
disease process and its pattern of behavior, the
treatment options have evolved accordingly.
factors in determining the best treatment for
disease control. Patients should be counseled
and involved in the decision-making process.
14911—MANAGEMENT OF DUCTAL CARCINOMA IN SITU AND PAGET DISEASE
Mastectomy
Historically, mastectomy was the treatment of
choice for DCIS, with cure rates approaching
98% to 99%. Reported failure rates after mastectomy 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 ra te 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 successfully extended to DCIS. However, mastectomy 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 surveillance mammography. When DCIS is not multicentric but limited to one area within the
breast, the size of this region relative to the
sizeofthebreastisanimportantconsideration for whether mastectomy is indicated.
This is obviously relative and must be individually 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. Likewise, the inability to obtain h istologically
negative margins after multiple attempts is
another indication to proceed with mastectomy. 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 d isorders 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 experiences with BCT for DCIS, employing lumpectomy as the primary treatment modality with
or without local XRT (Table 11–3). These indicated compelling evidence in favor of BCT.
A strong argument for the use of adjuvant radiation 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 histopathologic 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 protocol B-17, a prospective randomized trial comparing 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 11–3Trials of Lumpectomy
With and Without Radiation for DCIS
NSABP
B-17
Number of
patients
Follow-up (yr) 12 4 4.4
RR Excision
alone
% Invasive 50% 50% 40%
RR Excision þ
XRT
% Invasive 30% 40% 50%
RR, Recurrence rate; XRT, radiation therapy.
813 1002 1030
32% 16% 14%
12% 9% 6%
EORTC
10853
UK
DCIS