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1403
Microinvasive Breast Carcinoma
Clinicopathologic Analysis of a Single Institution Experience
Ruth F. Padmore, M.D., Ph.D.1
Barbara Fowble, M.D.2
John Hoffman, M.D.3
Cindy Rosser2
Alexandra Hanlon, Ph.D.2
Arthur S. Patchefsky, M.D.1
1
Department of Pathology, Fox Chase Cancer
Center, Philadelphia, Pennsylvania.
2
Department of Radiation Oncology, Fox Chase
Cancer Center, Philadelphia, Pennsylvania.
3
Department of Surgical Oncology, Fox Chase
Cancer Center, Philadelphia, Pennsylvania.
Presented in part at the Annual Meeting of the
Royal College of Physicians and Surgeons of Canada, Toronto, Ontario, Canada, September 1998.
Dr. Padmore’s current address: Department of
Laboratory Medicine, The Ottawa Hospital, Ottawa,
Ontario, Canada.
Address for reprints: Arthur S. Patchefsky, M.D.,
Department of Pathology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA
19111.
Received April 30, 1999; revisions received August
6, 1999, October 26, 1999, and December 10,
1999; accepted December 10, 1999.
© 2000 American Cancer Society
BACKGROUND. Microinvasive breast carcinoma (MIC) has a good prognosis but
specific definitions have varied in the past, making the clinical significance of MIC
a subject of debate.
METHODS. Microscopic slides of 59 cases of breast carcinoma originally diagnosed
as MIC were reviewed retrospectively. Histologic parameters were correlated with
clinical findings and outcome to define diagnostic criteria better.
RESULTS. On review, the 59 cases were recategorized as follows: pure DCIS (N ⫽
16), DCIS with foci equivocal for microinvasion (N ⫽ 7), DCIS with ⱖ 1 focus of
microinvasion (N ⫽ 11), T1 invasive carcinomas with ⱖ 90% DCIS (N ⫽ 18), and T1
tumors with ⬍ 90% DCIS (N ⫽ 7). The MIC cases in the current study averaged 3
separate foci of early infiltration outside the basement membrane, each one not ⬎
1.0 mm. The mean follow-up was 95 months. Six patients (10%) had only local
recurrence: 1 case each in patients with equivocal microinvasion, microinvasion,
and T1 tumors with ⬍ 90% DCIS and 3 cases among the patients with T1 tumors
with ⱖ 90% DCIS. Four patients, all with T1 tumors with ⱖ 90% DCIS, had distant
failure (7%). In the MIC group, only one patient developed a local recurrence after
breast conservation. No patient had axillary lymph node metastasis. For the entire
series, factors associated with local recurrence were younger age, breast conservation versus mastectomy, and close surgical margins. The only factor associated
with distant failure was the size of the DCIS component. Seven patients with T1
tumors with ⱖ 90% DCIS experienced local or distant failure and 5 of these (71%)
developed progressive disease or died of disease. All other patients who developed
a recurrence were disease free at last follow-up. In a retrospective series, poorer
outcome in carcinomas with ⱖ 90% DCIS may be related to the greater likelihood
of missed larger areas of invasive carcinoma. Therefore, meticulous and extensive
sampling of these carcinomas is required.
CONCLUSIONS. MIC as defined has a good prognosis. It has a different biology than
T1 invasive carcinoma with ⱖ 90% DCIS, which may progress and cause death.
Large tumors with multiple foci of microinvasion may have metastatic potential.
Cancer 2000;88:1403–9. © 2000 American Cancer Society.
KEYWORDS: breast neoplasms, microinvasive breast carcinoma, risk factors, metastasis.
C
arcinoma of the breast increasingly is being diagnosed at an
earlier stage because of routine screening mammography, with
more cases being diagnosed at the critical juncture between in situ
and invasive carcinoma. There have been many attempts to identify
such cases as microinvasive carcinoma (MIC), but definitions have
varied widely, making the usefulness of distinguishing MIC as a
distinct category of breast carcinoma open to question.1 At one end of
the spectrum is the definition of MIC given by Silverstein et al.,2 i.e.,
with 1 or 2 microscopic foci of possible invasion not ⬎ 1 mm in
1404
CANCER March 15, 2000 / Volume 88 / Number 6
greatest dimension. A similar definition has been used
more recently by Silver and Tavassoli3 that categorizes
MIC as a single focus of invasive carcinoma (IC) ⬍ 2
mm or up to 3 foci of invasion, each ⱕ 1 mm in
greatest dimension. Additional definitions occur in the
literature with this general philosophy, not all of
which limit the allowable number of invasive foci.4-8
At the other end of the spectrum of definitions is that
of Solin et al.,9 which defines MIC as the maximal
extent of IC comprising ⬍ 10 % of the tumor, with ⱖ
90% ductal carcinoma in situ (DCIS). These varying
definitions of microinvasion (e.g., such as that of
Wong et al.10) have been a source of nonuniformity in
the analysis of the clinical outcome, which has led to
uncertainty regarding the separation of MIC from
DCIS on the one hand and, conversely, from small ICs.
In an attempt to test the efficacy of the various definitions of MIC, we reviewed cases originally diagnosed
as MIC at our institution and stratified the degree of
invasion into definable groups to correlate each histologic group with clinical outcome. Although such
stratification resulted in fewer cases per group and
hampered statistical analysis, this allowed us to better
observe the biology of early invasive breast carcinoma.
MATERIALS AND METHODS
The clinical history and pathology material of 67 patients diagnosed with MIC at the Fox Chase Cancer
Center (FCCC) between 1982–1992 were reviewed
from the records of the tumor registry and the Departments of Radiation Oncology and Surgery. Cases were
approximately evenly divided between patients first
biopsied at other institutions and those whose first
surgery was at FCCC. Informed consent was obtained
from all subjects. All pathology materials and all available slides were reviewed by two pathologists (R.F.P.
and A.S.P.) together and a consensus diagnosis was
reached. As expected, these cases proved to be a
mixed population of tumors ranging from DCIS to
fully invasive ductal carcinoma (IC). Eight of the 67
cases were excluded from further analysis because of
the following reasons: unavailability of slides for
pathologic review (5 cases), lobular carcinoma in situ
(LCIS) only (1 case), lack of clinical follow-up (1 case),
and 1 case that on histologic review was interpreted as
a 1.2-cm IC.
An average of 16 microscopic slides of breast tissue were reviewed for each case, (range, 2– 41 slides).
Fewer slides were available, on average, from 13 cases
comprised entirely of outside slide review material
(average, 10 slides per case) versus 46 cases with at
least 1 surgical procedure performed at FCCC (average, 18 slides per case). Tumor size, particularly in this
retrospective series, was difficult to measure. As sug-
gested by Lagios,11 we attempted to arrive at the best
possible estimate of tumor size by utilizing all available information, including mammographic size,
macroscopic pathologic size, size measured from histologic sections, and the number of consecutive histologic slides involved. The size of the DCIS and IC
were measured separately to conform with current
TNM guidelines. Nuclear grade of DCIS and IC was
estimated using previously published criteria.12,13
For patients treated with breast-conserving surgery, tumor margins were assessed microscopically
from the available slides using an ocular micrometer.
Tumor ⬎ 2 mm away from the inked margin was
considered a negative margin. Tumor painted by ink
was considered a positive margin. Tumors in between
these two confines were considered close. In some
cases, the tumor margins were assessed macroscopically to be negative but no histologic sections were
taken, or the slides of a reexcision specimen were not
available for review but the surgical pathology report
indicated the margins were negative. These were considered as negative by macroscopic examination or by
report but were unconfirmed histologically. In some
cases, neither the slides nor the report of reexcision
specimens were available for review, or no assessment
of tumor margins was made; these cases were considered as indeterminate. Five of 13 cases (38%) comprised entirely of outside slide review material had
histologically verifiable margins. Tumor margins were
assessed histologically in 35 of 46 cases (76%) with at
least 1 surgical procedure performed at FCCC.
The range of tumors analyzed in this study appears to represent a morphologic continuum from
DCIS to small ICs that straddle the variety of definitions of microinvasion that have been proposed. The
groupings selected in this study were chosen to supply
nonoverlapping categories that could be compared
and related readily to the American Joint Committee
on Cancer staging system (TNM),14 as well as taking
into account the extent of the in situ and invasive
components (Table 1).
Tumors were segregated as showing no invasion
(pure DCIS). Another group of tumors predominantly
was DCIS, but showed focal penetration or breaching
of the ductal perimeter by a few cells that appeared
disassociated and unattached to the epithelial basement membrane (early microinvasion) (Fig. 1B).
These foci always were accompanied by a stromal
response comprised of scattered chronic inflammatory cells arranged within pale staining loose arrays of
new collagen. In addition to these qualitative aspects,
the total number of such areas was counted for each
case.
There also were cases that showed the character-
Microinvasive Breast Carcinoma/Padmore et al.
TABLE 1
Number of Patients in Each Histologic Group
1405
currence, age, and histologic parameters were evaluated using the chi-square test.
Histology
No. of patients (%)
Pure DCIS
Equivocal for microinvasion
Early microinvasion
Late microinvasion
T1 tumors, ⱖ 90% DCIS
T1 tumors, ⬍ 90% DCIS
16 (27%)
7 (12%)
5 (8%)
6 (10%)
18 (31%)
7 (12%)
59 (100%)
DCIS: ductal carcinoma in situ.
istic periductal stromal reaction of early microinvasion, but the presence of detached epithelial cells outside the basement membrane was a matter of debate
or equivocal (Fig. 1A). These cases were segregated
into a separate category as showing “equivocal microinvasion” for the purpose of further analysis.
Late microinvasion (Fig. 1C) was defined as a progression of early microinvasion. These predominantly
were DCIS, but showed areas of definite stromal infiltration by groups of more than a few loosely cohesive
carcinoma cells that remained close to the epithelial
basement membrane but infiltrated to a greater degree than that observed in early microinvasion. None
of these invasive areas measured ⬎ 1.0 mm in greatest
dimension as viewed with the ocular micrometer.
These cases also were analyzed quantitatively for the
number of such invasive foci, similar to those in early
microinvasion.
The next group was comprised of ICs ⬎ 1 mm (T1;
range, 0.15– 0.9 cm) comprised of a maximum of 10%
IC and thereby comprised of at least 90% in situ carcinoma as judged from the areas of tumor involvement on the microscopic slides (Fig. 1D). Also included in this group was 1 exceptional case of an 8-cm
DCIS with 17 foci of microinvasion.
The final group was comprised of IC ⬎ 1 mm (T1;
range, 0.3– 0.9 cm), in which the invasive component
comprised ⬎ 10% of the tumor.
Patients treated by either breast conservation
(lumpectomy and radiation therapy) or mastectomy
were studied. Follow-up of all cases was obtained
from patient charts, the files of the tumor registry, and
the data bank of the Department of Radiation Oncology. Overall survival, cause specific survival, and recurrence free survival were estimated using KaplanMeier methodology. A local regional recurrence was
defined as a recurrence in the ipsilateral breast, chest
wall, or axillary lymph nodes. All other recurrences
were considered as distant. Associations between re-
RESULTS
Review of the study group of 59 breast carcinomas
originally labeled as MIC resulted in the tumors being
reclassified as follows: 16 cases of pure DCIS, 7 equivocal for microinvasion, 5 microinvasive with focal
breach of the basement membrane (early microinvasion), 6 microinvasive ⱕ 1 mm (late microinvasion), 18
invasive carcinomas of T1 (⬎ 1 mm) with ⱖ 90% DCIS,
and 7 invasive carcinomas of T1 (⬎ 1 mm) with ⬍ 90%
DCIS (Table 1). Within the T1 invasive tumors with ⱖ
90% DCIS, 1 case was T1b IC and 1 case was a large,
8-cm DCIS with 17 foci of microinvasion; the remainder all were T1a ICs. The group of T1 invasive tumors
with ⬍ 90% DCIS was comprised of 3 cases with T1a
ICs and 4 cases with T1b ICs.
Analysis of MICs
The total number of MICs was 11. During the same
time period as these cases, 1610 patients with breast
carcinoma were treated at FCCC for an estimated incidence rate of MIC of 0.68%. The clinicopathologic
features of the 11 cases of MIC are presented in detail
in Table 2 and are summarized in Table 3. Surprisingly, in this small group, there were three cases of
contralateral breast carcinoma (one case each of
DCIS, medullary carcinoma, and IC, not otherwise
specified) and three cases of other malignancies (one
each of melanoma, colon carcinoma, and malignant
mixed mesodermal tumor of the ovary). A history of
breast carcinoma in first-degree relatives was elicited
in 4 patients (36%). It is interesting to note that two
patients with MIC had both contralateral breast tumors as well as other malignancies. The only death
among the MIC cases was the patient in Case 1, who
died of malignant melanoma with no evidence of recurrent breast carcinoma.
Surgical management was nearly equally divided
between lumpectomy (six cases) and mastectomy (five
cases). All 11 MIC patients underwent axillary lymph
node dissection; none had positive lymph nodes. All
patients who underwent lumpectomy received radiation therapy, whereas none of the patients undergoing
mastectomy did.
The average size of the DCIS was 2.5 cm (range,
1.2– 6.1 cm). In the majority of cases the DCIS was high
grade (9 of 11 cases; 82%). Comedo-type DCIS was the
most common architectural pattern observed (7 of 11
cases; 64%). LCIS accompanied MIC in 1 case (9%).
The mean number of foci of microinvasion was three
(range, one to six). Approximately 67% of cases had ⱖ
2 foci of microinvasion. Three of 6 patients treated by
1406
CANCER March 15, 2000 / Volume 88 / Number 6
FIGURE 1. (A) Ductal carcinoma in
situ (DCIS) with foci equivocal for microinvasion (H & E, ⫻175). (B) DCIS with
early microinvasion (H & E, ⫻350). (C)
DCIS with late microinvasion (H & E,
⫻350). (D) Small invasive ductal carcinoma (T1a). The breast lobule shows
both DCIS (left) and invasive carcinoma
(right) (H & E, ⫻70).
lumpectomy and radiation therapy underwent reexcisions as a separate surgical procedure; of these, 2
patients (67%) had residual tumor present in the reexcision specimens. Final margins were negative histologically or by report in 9 of 11 patients (82%), indeterminate in 1 patient (9%), and histologically close
in 1 patient (9%). One of six patients treated with
breast conservation developed a local recurrence
(Case 7). The reportedly negative surgical margins in
this case could not be confirmed by histology because
the slides were not available for review.
Analysis of Treatment Failures
Of the 59 breast carcinomas retrospectively reviewed,
6 patients developed local recurrences, 3 patients developed distant metastases, and 1 patient developed
both local and distant recurrences.
Only one of the recurrences occurred among the
MIC cases. This was a local recurrence of DCIS (Case
7 in Table 2). This patient had histologically unverified
tumor margins in the original specimen (slides not
available for review), and was treated with salvage
mastectomy. At last follow-up this patient was without
evidence of disease, 2 months after the recurrence.
There were no recurrences in the 16 patients with
pure DCIS. One patient with equivocal microinvasion,
3 with T1 tumors with ⱖ 90% DCIS, and 1 with T1
tumor with ⬍ 90% DCIS developed local recurrences.
Of these five local recurrences, three had close margins and one had margins verified by macroscopic
examination only. Only one of the locally recurrent
cases had histologically verified negative tumor margins. The only uncontrolled local recurrence occurred
in a patient with a T1 tumor with ⱖ 90% DCIS. All
three patients with distant metastases and the single
patient with both a local and distant recurrence presented with T1 tumors with ⱖ 90% DCIS. One of these
patients died of disease and the remaining two patients showed progression of their metastatic disease
at last follow-up.
Only 1 of the entire study group of 59 patients had
lymph node metastasis at presentation. This patient
had a T1a invasive tumor with ⱖ 90% DCIS and 4 of 7
positive axillary lymph nodes. After mastectomy, chemotherapy, and hormonal therapy, the patient was
without evidence of disease at last follow-up.
Two deaths from causes unrelated to the initial
breast carcinoma occurred within the study group of
59 patients during follow-up. Neither of these patients
manifested recurrence of their original breast tumors.
Patients who developed local or distant recurrences were significantly younger at the time of diagnosis than patients without recurrence. The mean age
at the time of initial diagnosis was 48 years for all
patients with local recurrence and 45 years for all
patients with distant failures, which was approxi-
Microinvasive Breast Carcinoma/Padmore et al.
1407
TABLE 2
Actual Microinvasive Breast Carcinoma Cases (Including Early and Late Microinvasive Carcinomas)
Case
no.
Age
(yrs)
Presentation
Treatment
Size DCIS
(cm)
Grade
DCIS
Histologic type
DCIS
No. foci
microinv
1
81
Mam
MRM
2.5
High
Comedo
3
2
67
Mam
Lump ⫹ reex
1.4
Inter
Pap/solid
3
3
4
5
6
36
41
69
70
Clin-excor nipple
Clin-mass
Clin-mass
Mam
MRM
MRM
MRM
Lump
2.0
1.5
3.6
1.3
High
High
High
Inter
Comedo
Comedo
Comedo
Solid
3
6
1
1
7
48
Clin-mass
Lump ⫹ reex
3.0
High
Micropap
2
Neg histol
Neg histol
Neg histol
Neg macroscopic
exam
Neg report
8
40
Clin-mass
MRM
6.1
High
6
Neg histol
9
56
Clin-mass
Lump
2.8
High
Crib/micropap/
apocrine
Comedo
3
Neg histol
Mam
Mam
Lump ⫹ reex
Lump
2.5
1.2
2.5
High
High
Comedo
Comedo
1
1
3 foci
Neg histol
Indeterminate
10
47
11
49
Mean 55
Margins
Tumor in reex
Neg macroscopic
exam
Close DCIS
Outcome (mos after
diagnosis)
DOC (85)
Residual DCIS ⫹
maybe
microinv
NED (101)
NED (94)
NED (102)
NED (98)
NED (130)
Residual, type
unknown
No residual
Local recur DCIS (24), NED
(26)
NED (147)
NED (alive with progressive
MMMT) (60)
NED (121)
NED (124)
(99 months)
DCIS: ductal carcinoma in situ; microinv: microinvasions; reex: reexcision; Mam: mammographic; MRM: modified radical mastectomy; neg: negative; exam: examination; DOC: dead of other causes; Lump:
lumpectomy; Inter: intermediate; Pap: papillary; NED: no evidence of disease (months of follow-up); Clin: clinically palpable; excor: excoriation; histol: histology; micropap: micropapillary; recur: recurrence; crib:
cribriform; MMMT: malignant mixed mesodermal tumor.
TABLE 3
Characteristics of Microinvasive Breast Carcinoma
TABLE 4
Actuarial Survival
Characteristics
Microinvasive
breast carcinoma
Mean age (yrs) (range)
First-degree relative with breast carcinoma
Contralateral breast carcinoma
Other carcinoma
Presentation: clinical (mean age)
Presentation: mammographic (mean age)
Lumpectomy ⫹ XRT (mean age)
Mastectomy (mean age)
Positive lymph nodes
55 (36–81)
4/11 (36%)
3/11 (27%)
3/11 (27%)
6/11 (55%) (48 yrs)
5/11 (45%) (63 yrs)
6/11 (55%) (56 yrs)
5/11 (45%) (55 yrs)
0/11 (0%)
Histologic group
Pure DCIS
Equivocal
microinvasion
Microinvasion
T1 tumors, ⱖ 90% DCIS
T1 tumors, ⬍ 90% DCIS
No. of
patients
5-yr
overall
5-yr cause
specific
5-yr recurrence
free
16
7
100%
100%
100%
11
18
7
100%
100%
100%
100%
One regional
recurrence
100%
100%
One regional
recurrence
a
91%
81%
a
DCIS: ductal carcinoma in situ.
a
Groups were too small to calculate 5-year recurrence free survival.
XRT: radiation therapy.
mately 10 years younger than the mean age at presentation of the group as a whole (57 years) (P ⬍ 0.03).
Both local and distant recurrence was related significantly to the size of the DCIS and not to the size of
the invasive component. The mean size of the in situ
component in the locally recurrent cases (2.7 cm) and
distant failures (5.6 cm) was greater than that of the
study group as a whole (2.2 cm) (P ⬍ 0.001). The size
of the invasive component was not found to be related
to recurrence.
In the entire study, only 1 of 30 patients (3%) with
histologically verified negative resection margins (⬎ 2
mm) developed a local recurrence (P ⬍ 0.01). Although all patients with local failure only initially were
treated with breast-conserving therapy, the local failure rate can be ascribed to the tumor margin status
rather than the treatment modality. Similarly, all patients who failed distantly underwent mastectomy as
their initial treatment.
Actuarial survival for MIC and for the other histologic groups is presented in Table 4. For this study, we
chose to include in the T1 tumors with ⱖ 90% DCIS
group the case of an 8-cm DCIS with 17 foci of microinvasion and pulmonary metastasis. In our opinion,
this case clearly falls outside the concept of MIC.
1408
CANCER March 15, 2000 / Volume 88 / Number 6
DISCUSSION
MIC is an uncommon histologic subtype of breast
carcinoma. The referral service of the Armed Forces
Institute of Pathology reports an incidence rate of
2.4%.3 The incidence rate in the current series, based
on cases treated at FCCC, an oncologic center, is
0.68%. The actual rate of incidence in the general
population most likely is even lower. MIC presents
over a wide range of ages; other studies using comparable definitions of MIC show a range of 32– 84 years at
presentation, with the average age in the sixth decade
of life (range, 50 –59.8 years).3,15,16 This is similar to the
current series, in which patients presented at an average age of 55 years (range, 36 – 81 years). Recent
series using similar definitions report that MIC presents as a palpable mass in 19 –50% of cases.3,15,16 This
is similar to our finding that 45% of patients in the
current study presented with a palpable mass. MIC
has been found to be more likely to present with a
palpable mass than DCIS,15 but a comparable comparison group was not part of the current study. MIC
most often is associated with comedo-type or other
high grade DCIS, and usually has more than one focus
of microinvasion.2,3,15,16 In the current series 9 of 11
patients (82%) had high nuclear grade, and the average number of invasive foci was 3. Thus our cases fit
the general clinicopathologic profile of other recent
series using comparable definitions.3,15,16 The occurrence of bilateral breast carcinoma, ICs at other sites,
and 33% of patients with a first-degree relative with
breast carcinoma may suggest a possible common
oncogenic factor, with MIC as an expression of the
phenotype. Further investigation of this possibility
may be informative. An example of this already occurs
in breast carcinoma, in the association of poorly differentiated, estrogen receptor negative carcinoma
with the BRCA1 mutation.17,18
MIC appears to have a low rate of recurrence;
some investigators have found no recurrences,3,10
whereas Silverstein15 found 2 cases of recurrence (2 of
21 cases; 9.5%) after a median follow-up of 85 months.
Our own experience shows that 1 recurrence occurred
in our group of 11 MICs. This local recurrence developed in a patient with histologically unconfirmed tumor margins. Inadequate local control also accounted
for a single local recurrence in Silverstein’s series of
MIC.15 The importance of obtaining histologically verified negative tumor margins also is highlighted by the
one case in the current study with equivocal microinvasion that locally recurred but had close histologic
margins.19 This latter group of cases would be included in some studies of MIC, but we have chosen to
analyze them separately to discern any differences in
the behavior of a spectrum of cases starting with the
earliest possible evidence of tumor invasion.
The one patient with 17 foci of microinvasion who
developed lung metastases most likely would be excluded from studies of MIC using current criteria20
and in our study we consider this a T1 tumor with ⱖ
90% DCIS. In recent study, Zavotsky et al.21 described
a similar case of MIC with multiple foci suspicious for
microinvasion that were ⬍ 1 mm. A single sentinel
lymph node was positive for a 0.3-cm metastasis. The
patient developed a malignant pleural effusion 29
months after breast surgery. Therefore, evidence is
accumulating in the literature that cases of DCIS with
multiple foci of microinvasion have significant metastatic potential and should be distinguished from MIC
without multiple foci of microinvasion.
Axillary lymph node metastasis in MIC has been
reported in a minority of cases (range, 3–18%)9,16,22-25
or not at all,3,10,15 depending on the definition of MIC
used in each study. A recent study of MIC using sentinel lymph node mapping found 14.3% of patients (2
of 14) with lymph node metastases.21 None of the
patients with MIC in the current study had lymph
node metastases. Silverstein15 also noted no lymph
node metastases in 17 cases. In comparison, 2 of 321
lymph node dissections performed for DCIS were positive (0.6%), which emphasizes the need to compare
the treatment and outcome of MIC with DCIS and not
normal controls.15
Seven failures in the current study, both local and
distant, occurred in patients with invasive (T1) carcinoma with ⱖ 90% DCIS. Failure within this group
appeared to have a poor prognosis because 5 of 7
patients (71%) had progressive disease or died of disease. In IC, studies have found a higher rate of local
recurrence26 and metastatic disease27 in cases in
which the invasive breast carcinoma is associated with
an extensive intraductal component and the patient is
young.25,28 Both of these features were associated with
treatment failure in the current series. Such tumors
should not be included in any definitions of MIC.
Treatment failure was associated with the size of
the DCIS rather than the size of the invasive tumor.
Because the current study is a retrospective series, this
might be due to the fact that tumors bearing the larger
burden of DCIS might not have been sampled enough
to detect areas of frank invasion.
MIC, as defined by Silverstein et al.2 and Silver
and Tavassoli,3 has a good prognosis. In the current
series no cases with an average of 3 separate foci of ⱕ
1.0 mm microinvasion recurred, unless tumor margins
were unconfirmed histologically. Cases of MIC with
multiple foci of microinvasion may identify a group
with metastatic potential, although the threshold
Microinvasive Breast Carcinoma/Padmore et al.
number of such foci is unknown. For this reason, we
would recommend that all tumors that show a focus of
invasion ⱕ 1 mm be examined thoroughly to document the number of such foci in the tumor, as well as
the possibility of larger areas of invasion. At this time,
MIC as defined by Silverstein et al.,2 Silver and Tavassoli,3 and the American Joint Committee on Cancer
staging system (TMN)14 should be adhered to if the
term is to have any clinical relevance. A multiinstitutional study with the accrual of more cases studied
uniformly may cast light on the question of the threshold number of microinvasive foci that will predict
more aggressive behavior. The current study has
shown that MIC should be distinguished from T1 invasive tumors with ⱖ 90% DCIS. These latter tumors
have aggressive potential and are associated with a
poor outcome, especially when occurring in younger
women. Such cases illustrate that there is no place for
any definition of MIC based only on the percentage of
DCIS in the tumor.
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