DOI:10.2214/AJR.07.2784
AJR 2008; 190:496-504
© American Roentgen Ray Society
Correlation of Whole-Breast Vascularity with Ipsilateral Breast Cancers Using Contrast-Enhanced MDCT
Doo Kyoung Kang1,
Eun Jin Kim1,
Ho Sung Kim1,
Joo Sung Sun1 and
Yong Sik Jung2
1 Department of Diagnostic Radiology, Ajou University School of Medicine, San 5,
Wonchon-dong, Yeongtonggu, Suwon, Kyongi-do 442-721, South Korea.
2 Department of General Surgery, Ajou University School of Medicine, Suwon,
Kyongi-do, South Korea.
Received June 26, 2007;
accepted after revision August 3, 2007.
Address correspondence to D. K. Kang
(kdklsm{at}ajou.ac.kr).
Abstract
OBJECTIVE. The purpose of our study was to assess the increase in
whole-breast vascularity in patients with unilateral breast cancer and
correlate that increase with prognostic factors of breast cancer.
MATERIALS AND METHODS. We performed 16-MDCT on 143 consecutive
patients with histologically confirmed breast cancer. One hundred three of
these 143 patients were finally enrolled in the study after exclusion of
patients with bilateral breast cancer, previous history of neoadjuvant
chemotherapy, breast surgery, or lack of surgical confirmation. Breast
vascularity was assessed according to the number, length, and conspicuity of
vessels on maximum-intensity-projection images. Increase of whole-breast
vascularity of the cancer-bearing breast was categorized as not increased,
mild, moderate, or prominent compared with the contralateral breast. Breast
vascularity was then correlated to prognostic factors including tumor size,
lymph node status, cancer stage, nuclear and histologic grade, presence of an
extensive intraductal component, presence of hormone receptors, and expression
of C-erb-B2.
RESULTS. In 77 (74.8%) of 103 patients, breast cancers were found to
be associated with ipsilateral increased whole-breast vascularity. In the 77
patients with increased vascularity, prominent, moderate, and mild vascularity
were shown in 21 (27.3%), 23 (29.9%), and 33 (42.9%) patients, respectively.
Ipsilateral increased vascularity was related to tumor size, lymph node
status, cancer stage, nuclear grade, and histologic grade. The presence of
extensive intraductal component and hormone receptors and the expression of
C-erb-B2 were not related to ipsilateral increased vascularity.
CONCLUSION. Breast cancers were found to be associated with
ipsilateral increased whole-breast vascularity in a significant percentage of
patients. Increased whole-breast vascularity indicated the growth and
metastatic potential of a breast cancer.
Keywords: angiogenesis • breast cancer • CT • vascularity
Introduction
Angiogenesis (also known as neovascularization) is the formation of new
capillaries from the existing vascular network
[1]. Because vascular blood
flow provides nutrients for tumor growth and a mechanism for hematogenous
spread of malignant cells [2,
3], tumor angiogenesis has been
reported to be an independent prognostic indicator in breast cancer
[4–8].
Although tumor vasculature has mostly been investigated by immunohistochemical
methods using factor VIII staining of endothelial cells to determine
microvessel density (MVD) [9,
10], this invasive method is
difficult to reproduce and standardize
[11]. Many imaging
angiogenesis methods in vivo have recently been developed, including color
Doppler sonography [12] and
contrast-enhanced MRI [13,
14], and most of them have
focused on measurement of angiogenesis in the immediate vicinity of the
growing tumor. However, vascularity can increase not only within a breast
cancer lesion but also in the ipsilateral breast as a whole. Recently, some
studies have estimated whole-breast vascularity by laser Doppler perfusion
imaging [15], PET
[16], and MRI
[17–19]
and found an association between breast cancer and an ipsilateral increase of
blood flow.
Although contrast-enhanced CT of the breast has been used for assessment of
axillary lymph node metastasis
[20,
21], diagnosis of local
recurrence after breast-conserving surgery
[22], or imaging intraductal
extension of breast cancer preoperatively
[23], it can also show tumor
vascularity. Especially, MDCT can display high-quality angiographic images
because of improved temporal and spatial resolution. However, to the best of
our knowledge, there has been no study on imaging vascularity of breast cancer
using contrast-enhanced MDCT. The purpose of this study was to quantitatively
evaluate ipsilateral whole-breast vascularity using MDCT in patients with
unilateral breast cancer and correlate it with prognostic factors of breast
cancer.
Materials and Methods
Patients
Between August 2003 and May 2007, 143 consecutive women with breast cancer
diagnosed by percutaneous biopsy underwent MDCT. Considering radiation
exposure, we carefully applied the indication for MDCT. We first restricted
the application of MDCT only to preoperative patients with histologically
proven breast cancer. The primary inclusion criterion for preoperative MDCT
was a suspicion of regional lymph node or remote thoracic metastasis in
advanced breast cancer patients in whom mastectomy was planned as treatment.
Another important inclusion criterion was to evaluate the spread and local
extent of breast cancer in patients for whom MRI was not available.
At our hospital during the study period, 655 patients were diagnosed with
primary breast cancer by percutaneous or excisional biopsy. Only 143 of them
underwent MDCT for preoperative evaluation, and most of remaining patients
underwent breast MRI. With 40 patients excluded for bilateral breast cancer
(n = 2), previous history of neoadjuvant chemotherapy (n =
7), previous breast surgery (n = 26), or lack of surgical
confirmation (n = 5), 103 patients (age range, 22–79 years;
mean age, 46.7 years) were finally included in the image analysis, and all of
them underwent histopathologic examination of the breast lesion after
breast-conserving surgery (n = 37) and mastectomy (n = 66).
The lesions consisted of 88 invasive ductal carcinomas, not otherwise
specified (NOS); four mucinous carcinomas; two medullary carcinomas; one
metaplastic carcinoma; six ductal carcinoma in situ with microinvasion; and
two pure ductal carcinoma in situ (DCIS)
(Table 1). The study was
approved by the ethics committee of our institution, and informed consent was
obtained from all patients.
Imaging Studies
Mammograms were obtained from all patients using a DMR (GE Healthcare)
mammography unit. Whole-breast sonography was performed for all patients using
an Acuson Sequoia (Siemens Medical Solutions) sonography system with an
8-13–MHz linear array transducer at our institute. All sonographic
examinations were performed by one breast radiologist. The mammograms and
breast sonograms were interpreted by the same radiologist.
We used a 16-MDCT scanner (Somatom Sensation, Siemens Medical Solutions)
with the following technical parameters: acquisition time, 420 ms/rotation;
image matrix, 512 x 512; field of view, 35–38 cm; tube voltage,
100 kVp; tube current, 100 effective mA; 1.5-mm collimation; and pitch, 4. The
volume CT dose index (CTDIvol) ranged from 3.1 to 4.5 mGy for each
breath-hold acquisition. We scanned patients from the level of the lower neck
to the lower edge of the lung. Three breath-hold acquisitions were obtained
before and 90 seconds and 5 minutes after an IV rapid bolus administration of
nonionic contrast material. We infused 100 mL of nonionic contrast material
(iomeprol, 400 mg I/mL [Iomeron, Ilsung Pharmaceuticals]) at a rate of 3.0
mL/s. The data were reconstructed at 1.5-mm slice thickness and in 1-mm
increments. All patients underwent MDCT in the supine position because it
allows surgical simulation on 3D data displays. After reconstruction, the
images were transferred to a workstation. Multiplanar reformation (axial,
oblique coronal, and sagittal) and maximum-intensity-projection (MIP) images
were used for evaluation of the tumors. Each multiplanar reformation image was
created with a 3-mm slice thickness and a 2-mm increment. MIP images of the
breast were generated, eliminating other structures such as bone and the
pectoral muscles. The window level and width settings were adjusted freely on
the PACS system (PIViewSTAR, version 5025, Infinitt). The ranges of the
appropriate window width and level settings were 200–250 and 40–60
H, respectively, for evaluation of the breast.
Image Analysis
Two experienced independent radiologists, who were blinded to the clinical
data and the final diagnosis, retrospectively evaluated and categorized
whole-breast vascularity separately and in consensus. Image analysis was
performed on MIP images obtained 90 seconds after injection of the contrast
material because pronounced enhancement of the primary mass and vessels is
usually seen in this time period
[24]. According to a
modification of Sardanelli's method
[17], a category was assigned
to each MIP image on the basis of the number of vessels seen and the length
and conspicuity of the vessels. The number of vessels per breast that were 3
cm or greater in length and 2 mm or greater in maximal transverse diameter
were counted. The degree of vascularity differences was classified as
"prominent" if the number of vessels in the cancer-bearing breast
was increased by three or more relative to those in the contralateral breast.
If the number of vessels increased by two in the ipsilateral breast, the
degree of vascularity was classified as "moderate"; if the number
of vessels increased by one, it was classified as "mild"; and if
the number of vessels in the ipsilateral breast was the same as or decreased
relative to that of the contralateral breast, the degree was classified as
"not increased." We also recorded whether perforating branches
were arising from the internal mammary artery or the lateral thoracic
artery.
Histopathologic Analysis
The whole specimen was thinly sliced and embedded in paraffin, and the
sections stained with H and E in each case were reviewed by one experienced
pathologist without knowledge of the results of the CT examination. The size
of the tumor was generally estimated from pathologic gross descriptions and
recorded with the largest cross-sectional dimension. However, if the
microscopic tumor measurement of the largest dimension was substantially
greater than the largest gross measurement or substantially smaller than the
gross measurement, the microscopic measurement was used for staging. Because
the pathologic determination of tumor size for the classification of T stage
is a measurement of the invasive component, measurement of the invasive
component exclusive of peripheral extensions of the intraductal component was
recommended, whereas contiguous peripheral invasive elements were included in
the measurement of tumor size.
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Fig. 1A —67-year-old woman with invasive ductal carcinoma. Oblique
coronal reconstruction image shows lobular mass (arrow) with
spiculated margin and homogeneous internal enhancement in left breast.
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Fig. 1B —67-year-old woman with invasive ductal carcinoma. On
maximum-intensity-projection (MIP) image, three vessels (arrows) are
counted in both breasts. As result, whole-breast vascularity in cancer-bearing
breast is not increased compared with contralateral breast. Patient underwent
total mastectomy and was diagnosed as having stage I (T1N0M0) cancer.
Histopathology confirmed invasive ductal carcinoma with nuclear grade of 3 and
histologic grade of 1.
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We measured the size of the largest tumor when a multifocal or multicentric
cancer was found. However, if invasive carcinoma was dispersed across the
entire tumor diameter, the largest dimension from point to point across the
entire invasive diameter was the measured tumor size. After the size
measurement, the specimens were evaluated according to the following
histopathologic features: histologic type of carcinoma; Black's nuclear grade
(1, poorly differentiated; 2, moderately differentiated; and 3, well
differentiated); modified Bloom-Richardson's histologic grade (1, well
differentiated; 2, moderately differentiated; and 3, poorly differentiated),
presence of extensive intraductal component (EIC); presence of hormone
receptors (estrogen receptor [ER], progesterone receptor [PR], expression of
C-erb-B2 oncogene), and N-stage status (presence and number of axillary lymph
node metastases). The overall stage of cancer was classified according to the
American Joint Committee on Cancer TNM staging of breast cancer
[25].
Statistical Analysis
Microsoft Excel 2000 software was used for the data collection. First,
interobserver variability was assessed by calculating the kappa value. The
patient age of each categorized group with ipsilateral whole-breast
vascularity was compared using one-way analysis of variance. Fisher's exact
test was used for the evaluation of the relation between breast vascularity
ipsilateral to the cancer and the BI-RADS descriptors or prognostic factors (T
status, N status, cancer stage, and nuclear and histologic grades). The
relations between breast vascularity ipsilateral to the cancer and presence of
EIC or hormone receptors were evaluated using a chi-square test. All
statistical analysis was performed on SPSS for Windows, release 13.0 (SPSS),
with p < 0.05 considered to indicate a significant difference.
Results
Ipsilateral Increased Vascularity in Cancer-Bearing Breasts
On MDCT, MIP images of the blood vessels of the breasts were clearly
depicted in all cases. Two readers in consensus found carcinoma of the breast
to be associated with ipsilateral increased vascularity in 77 patients (74.8%)
and not associated with increased vascularity in 26 patients (including 25
patients with balanced vascularity and one with decreased vascularity) (Fig.
1A,
1B). Of the 77 patients with
ipsilateral increased vascularity in the cancer-bearing breast, prominent,
moderate, and mild vascularity were shown in 21 (27.3%), 23 (29.9%), and 33
(42.9%), respectively (Figs.
2A,
2B,
3A,
3B,
4A,
4B,
4C).
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Fig. 2A —62-year-old woman with invasive ductal carcinoma. Oblique
coronal reconstruction image shows round mass (arrow) with spiculated
margin and heterogeneous internal enhancement in right breast.
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Fig. 2B —62-year-old woman with invasive ductal carcinoma. On
maximum-intensity-projection (MIP) image, two vessels (long arrows)
in right breast and one vessel (short arrow) in left breast are
counted. As result, cancer-bearing breast shows mild increased vascularity
compared with contralateral breast. Patient underwent total mastectomy and was
diagnosed as having stage I (T1N0M0) cancer. Histopathology confirmed invasive
ductal carcinoma with nuclear grade of 3 and histologic grade of 1.
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Fig. 3A —48-year-old woman with invasive ductal carcinoma. Oblique
coronal reconstruction image shows nonmasslike enhancement (arrows)
with segmental distribution and homogeneous internal enhancement in right
breast.
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Fig. 3B —48-year-old woman with invasive ductal carcinoma. On
maximum-intensity-projection (MIP) image, two vessels (short arrows)
in right breast and four vessels (long arrows) in left breast are
counted. As result, cancer-bearing breast shows moderate increased vascularity
compared with contralateral breast. Patient underwent total mastectomy and was
diagnosed as having stage IIB (T3N0M0) cancer. Histopathology confirmed
invasive ductal carcinoma with nuclear grade of 1 and histologic grade of 3.
Tumor is accompanied by extensive intraductal component.
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Fig. 4A —57-year-old woman with invasive ductal carcinoma. Oblique
coronal reconstruction images show irregularly shaped mass (short
arrow) with spiculated margin and peripheral rim enhancement in left
breast. There are multifocal satellite nodules (long arrows,
B) around main tumor.
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Fig. 4B —57-year-old woman with invasive ductal carcinoma. Oblique
coronal reconstruction images show irregularly shaped mass (short
arrow) with spiculated margin and peripheral rim enhancement in left
breast. There are multifocal satellite nodules (long arrows,
B) around main tumor.
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Fig. 4C —57-year-old woman with invasive ductal carcinoma. On
maximum-intensity-projection (MIP) image, one vessel (short arrow) in
right breast and four vessels (long arrows) in left breast are
counted. As result, cancer-bearing breast shows prominent increased
vascularity compared with contralateral breast. There are multiple metastatic
lymph nodes (arrowheads) at left axilla. Patient underwent total
mastectomy and was diagnosed as having stage IIIC (T2N3M0) cancer.
Histopathology confirmed invasive ductal carcinoma nuclear grade of 1 and
histologic grade of 3. Tumor is accompanied by extensive intraductal
component.
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There was a good agreement between the observers, with a kappa value of
0.635. In 95 (92.2%) of 103 patients, all of the examiners agreed that
whole-breast vascularity was clearly increased or not increased in the
ipsilateral breast, with a kappa value of 0.755
(Table 2). Perforating arterial
branches were arising from the ipsilateral internal mammary artery in 48
(46.6%) patients, from the lateral thoracic artery in 13 (12.6%) patients, and
from both in 42 (40.8%) patients.
Correlation Between Ipsilateral Increased Vascularity and BI-RADS Descriptors
MDCT showed the breast cancer in all cases. The CT finding of the main
tumor in 88 (85.4%) patients was enhanced mass, and CT findings in the
remaining 15 (14.6%) patients revealed a nonmasslike enhancement as a
malignant tumor (Fig. 3A,
3B). In the patients who had
findings that revealed nonmasslike enhancement, histopathology confirmed one
DCIS, five DCIS with microinvasion, seven infiltrating ductal carcinoma (IDC)
with EIC, and two IDC without EIC.
Of the 88 patients who had findings that revealed a mass, 41 cases (46.6%)
showed irregular shape, 82 cases (93.2%) showed irregular or spiculated
margin, and 34 cases (38.6%) showed rim enhancement (Fig.
4A,
4B,
4C). Of the 15 patients who had
findings that revealed nonmasslike enhancement, 11 cases (73.3%) showed
segmental distribution and eight cases (53.3%) showed clumped enhancement
(Fig. 3A,
3B). The results of the
analysis of ipsilateral increased breast vascularity versus BI-RADS
descriptors are presented in Table
2. Ipsilateral increased vascularity did not relate to any BI-RADS
descriptors.
Correlation Between Ipsilateral Increased Vascularity and Histopathologic Predictors
The results of the analysis of ipsilateral increased breast vascularity
versus the histopathologic prognostic predictors are presented in
Table 3. Two cases of DCIS were
excluded from all the statistical analysis. Also, specific types of breast
carcinoma and DCIS with microinvasion were excluded from the statistical
analysis of ipsilateral whole-breast vascularity versus nuclear and histologic
grade.
The mean maximum diameter of 101 invasive cancers was 28.8 ± 18.0
mm, ranging from 0.3 to 90 mm. There were 11 cases of minimal breast cancers:
six cases of DCIS with microinvasion and five cases of invasive cancer (< 1
cm in dimension). Ipsilateral increased vascularities were detected in eight
(72.7%) of 11 minimal cancers and in 67 (74.4%) of 90 nonminimal cancers, and
there was no significant difference between the two groups (p =
0.091).
Ipsilateral prominent increased vascularity was detected in two (5.0%) of
stage T1 (n = 40) versus two (66.7%) of T4 (n = 3), six
(13.6%) of N0 (n = 44) versus eight (50.0%) of N3 (n = 16),
one (3.7%) of stage I (n = 27) versus 10 (34.5%) of stage III
(n = 29), five (12.8%) of nuclear grade 1 (n = 39) versus
none of nuclear grade 3 (n = 9), and none of histologic grade 1
(n = 13) versus 16 (35.6%) of histologic grade 3 (n = 45)
(Fig. 5A,
5B,
5C,
5D,
5E). Ipsilateral increased
vascularity was related to T stage of tumor (p = 0.009), lymph node
status (p = 0.003), cancer stage (p = 0.001), nuclear grade
(p = 0.046), and histologic grade (p = 0.008). However, the
presence of EIC and hormone receptors, and expression of C-erb-B2 oncogene,
was not related to ipsilateral increased vascularity.
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Fig. 5A —Distribution of whole-breast vascularity (percentage of
corresponding women) in cancer-bearing breast corresponding to each prognostic
factor. Graphs show T stage (A), N stage (B), cancer stage
(C), nuclear grade (D), and histologic grade (E).
Ipsilateral increased vascularity correlated to the T stage of tumor
(p = 0.009), N stage (p = 0.003), cancer stage (p =
0.001), nuclear grade (p = 0.046), and histologic grade (p =
0.008).
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Fig. 5B —Distribution of whole-breast vascularity (percentage of
corresponding women) in cancer-bearing breast corresponding to each prognostic
factor. Graphs show T stage (A), N stage (B), cancer stage
(C), nuclear grade (D), and histologic grade (E).
Ipsilateral increased vascularity correlated to the T stage of tumor
(p = 0.009), N stage (p = 0.003), cancer stage (p =
0.001), nuclear grade (p = 0.046), and histologic grade (p =
0.008).
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Fig. 5C —Distribution of whole-breast vascularity (percentage of
corresponding women) in cancer-bearing breast corresponding to each prognostic
factor. Graphs show T stage (A), N stage (B), cancer stage
(C), nuclear grade (D), and histologic grade (E).
Ipsilateral increased vascularity correlated to the T stage of tumor
(p = 0.009), N stage (p = 0.003), cancer stage (p =
0.001), nuclear grade (p = 0.046), and histologic grade (p =
0.008).
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Fig. 5D —Distribution of whole-breast vascularity (percentage of
corresponding women) in cancer-bearing breast corresponding to each prognostic
factor. Graphs show T stage (A), N stage (B), cancer stage
(C), nuclear grade (D), and histologic grade (E).
Ipsilateral increased vascularity correlated to the T stage of tumor
(p = 0.009), N stage (p = 0.003), cancer stage (p =
0.001), nuclear grade (p = 0.046), and histologic grade (p =
0.008).
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Fig. 5E —Distribution of whole-breast vascularity (percentage of
corresponding women) in cancer-bearing breast corresponding to each prognostic
factor. Graphs show T stage (A), N stage (B), cancer stage
(C), nuclear grade (D), and histologic grade (E).
Ipsilateral increased vascularity correlated to the T stage of tumor
(p = 0.009), N stage (p = 0.003), cancer stage (p =
0.001), nuclear grade (p = 0.046), and histologic grade (p =
0.008).
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Discussion
Angiogenesis, the production of new blood vessels within tumors, is an
essential process for sustaining tumor growth and metastasis. The increased
vascularity of the breast in association with cancer may be attributed to
reduced flow resistance in the tumor vessels, the high metabolic demand of the
tumor, angiogenic stimulation of the whole breast, or a combination of these
factors [17]. Angiogenesis is
histopathologically evaluated in terms of tumoral MVD, which is measured by
immunohistochemical methods using factor VIII staining of endothelial cells or
CD31 antigen staining [2,
9], and MVD has been shown to
be predictive of metastasis either in axillary lymph nodes or at distant sites
(or both) in patients with invasive breast carcinoma—that is, the higher
the MVD, the more likely the tumors are to metastasize
[2,
3]. However, the measurement of
MVD requires an invasive procedure, either biopsy or surgical excision, and is
limited because of a random sampling error secondary to intratumoral
heterogeneity [8,
9]. Therefore, it would be
important to develop a simple and noninvasive in vivo technique to measure
angiogenesis.
Dynamic contrast-enhanced MRI has been used to examine microcirculation in
malignant tumors
[5–7].
MRI also enables assessment of ipsilateral vascularity as a whole and
observation of increased vascularity in cancer-bearing breasts, which could be
used as a sign of malignancy
[17–19].
Mahfouz et al. [18] showed an
association between breast cancer and a higher ipsilateral vascularity;
however, the sensitivity and specificity of this sign for the diagnosis of
malignancy were only 76.5% and 57%, respectively. Sardanelli et al.
[17] suggest that vascular
asymmetry could be considered a potential MRI sign of invasive breast cancer,
with sensitivity and specificity of 88% and 82%, respectively. On the other
hand, MDCT has recently been improved to acquire high-quality angiographic
images because of faster scanning, wider area of coverage, and higher
resolution of the volume data.
Similar to MRI, MIP images on MDCT obtained by postprocessing reveal not
only the presence of enhancing lesions but also the angiographic vascular map
of vessels within the breast. Importantly, the acquisition time for MDCT of
the breast is usually within 10 seconds. This time resolution is extremely
suitable for angiographic evaluation. Therefore, CT could be an excellent
alternative, particularly in the presence of MRI contraindications.
Furthermore, MDCT has some advantages
[25–27]:
The patient can be supine, thus allowing surgical simulation for breast
conservation using a 3D display; MDCT permits access to the lung, thoracic
wall, lymph nodes, liver, and bones in a single study and simultaneous
scanning of both breasts, which allows comparison of the affected breast with
the contralateral breast; and MDCT allows an easier approach to imaging-guided
needle aspiration and hookwire localization. In addition, because the
surrounding fat appears as low density, iodinated contrast enhancement of the
breast tumor is easily recognized with proper window width and level settings
without using a subtraction technique or fat suppression
[27].
The comparison of the vascularity of breasts in our study was a
quantitative procedure and revealed an acceptable level of interobserver
variability. Nevertheless, there was considerable disagreement between the two
observers. This was most likely due to difficulty of counting the vessels.
When two or more vessels branched off from one main vessel or they were
connected and networked with others, it was practically impossible to count
the exact vessel number. Therefore, more objective quantitative criteria
should be established in the future.
The present results showed that malignant breast neoplasms are associated
with a higher ipsilateral vascularity in a significant percentage (74.8%) of
patients. However, we could not show the specificity and accuracy because our
study population included only patients with biopsy-proven breast cancer.
Although ipsilateral increased vascularity is frequently associated with
ipsilateral invasive breast cancer, the question of whether this finding is
clinically valuable remains largely unanswered. Indeed, intermediate
sensitivity and specificity, which have been described in earlier MRI studies,
make it less reliable in individual patients
[17,
18]. Therefore, additional
study should be focused on differentiation of benign breast lesions or no
lesions.
MDCT has the advantage of simultaneously depicting vessels and enhancing
lesions, making it possible to assess their spatial relationship to each
other. Many signs of malignancy have been described by CT of the breast. Inoue
et al. [26] first reported the
diagnostic features of breast cancer on MDCT, and they included irregular
margins, irregular shape, and rim enhancement. Other findings on CT suggestive
of malignancy included thickening of overlying skin, presence of axillary
lymph node enlargement, invasion of the pectoralis muscle, and pleural
effusion [28]. In the present
study, all 88 cases (100%) with a mass had at least one or more of these
findings of malignancy, and the most sensitive (93.2%) descriptor for
malignancy was irregular or spiculated margins. Therefore, further studies are
necessary to determine whether the combination of breast vascularity and
traditional criteria should be used to increase specificity for detection of
breast cancer.
To our best knowledge, few reports exist on the relationship between
whole-breast vascularity and traditional prognostic factors. Sardanelli et al.
[17] suggest that the
dimension of cancer is probably not the key factor in the ipsilateral
prevalence of increased breast vascularity. However, they could not compare
the dimensions of cancers to ipsilateral increased vascularity because of the
small number of false-negative cases
[17]. Wright et al.
[19] also had difficulty
making significant correlations between higher ipsilateral vascularity and
infiltrating histology, multifocality, primary tumor size, or nodal status
because of the small number of patients
[19]. On the other hand, we
found a clear correlation between the presence of increased ipsilateral
vascularity and tumor size, regional lymph node status, cancer stage, and
histologic grade.
Considering tumor size, ipsilateral increased vascularities of minimal
cancers were detected in 72.7% of cases, which did not significantly differ
from 74.4% in nonminimal cancers (p = 0.091). These findings suggest
that tumor size probably is not the key factor in the ipsilateral prevalence
of increased breast vascularity; and other variables, such as angiogenic
stimulation or biologic aggressiveness, could be the major cause of increased
ipsilateral whole-breast vascularity
[17,
19]. However, in the present
study, we graded vascularity on the basis of the number of vessels instead of
the absence or presence of increased vascularity because the breast lesions of
all our patients had already been proven to be malignant, and ipsilateral
increased whole-breast vascularity was significantly related to the size of
the invasive component. Furthermore, our study population showed a relatively
large size of cancers, with a mean diameter of 28 mm, because of our inclusion
criteria, although the tumor diameter was normally distributed. Therefore,
only 11 cases with minimal breast cancer were included in this study. The
relationship between tumor size and increased vascularity should further be
pursued with a large population of patients with minimal breast cancer
[29].
The breast is supplied by the internal and lateral thoracic arteries;
however, the internal thoracic artery supplies a larger volume of the breast
than does the lateral thoracic artery
[7,
8]. Furthermore, tumor vascular
mapping also has therapeutic implications, particularly in patients who
receive agents that target tumor-induced angiogenesis: In intraarterial
chemotherapy, it is essential to accurately identify a feeding artery of the
tumor. In the present study, although considerable cases were supplied from
both internal and lateral thoracic arteries, most cases were supplied from the
internal thoracic artery rather than the lateral thoracic artery (46.5% vs
12.6%).
The greatest disadvantage of CT is the exposure of the breast to radiation.
Therefore, we restricted the application of breast CT to preoperative patients
who had cytologically or histologically proven breast cancer. Then, to reduce
the total radiation dose, we restricted the examination to only three phases.
Furthermore, MDCT offers an opportunity to obtain excellent images at a
reduced exposure with the selection of mA and pitch. In our study, the total
calculated radiation dose of one CT examination ranged from 9.5 to 13.5 mGy
because the CTDIvol ranged from 3.1 to 4.5 mGy for each breath-hold
acquisition. The radiation dose of our technique was markedly lower than that
of previous studies [26,
30], although it was three to
four times higher than that received during standard two-view mammography.
The dose is expected to be reduced further with the introduction of better
methods of using MDCT [24].
Boone et al. [31] showed that
80-kVp breast CT was comparable in dose with two-view mammography of 5-cm
breasts using their own special table and CT method. Nevertheless, the use of
CT for breast cancer imaging should be avoided as much as possible in clinical
practice. The risk of contralateral cancer is already greatly increased for
women who have had a breast cancer. From such a perspective, the use of breast
CT in a clinical setting should be restricted to patients who cannot undergo
MRI because of contraindications such as pacemakers or serious
claustrophobia.
Several limitations of our study should be taken into account. First, we
could not differentiate malignant from benign lesions using the difference of
vascularity in the whole breast because our study population consisted of
women who had biopsy-proven breast cancer. At present, CT is not the study of
choice to evaluate specific breast lesions. Therefore, MDCT is not generally
performed at our institute to differentiate malignant from benign breast
lesions. Second, our series included a small number of patients with pure
DCIS. Therefore, we could not evaluate the difference in vascularity between
invasive cancer and noninvasive cancer, which is known to have reduced
angiogenesis compared with invasive carcinoma
[32]. However, a total of
eight cases of DCIS with microinvasion were included in the present study, and
six (75%) of them revealed ipsilateral increased vascularity. Additional work
should be focused not only on patients with invasive cancer but also on
patients with in situ cancers. The third limitation of this study is that the
evaluation of whole-breast vascularity was performed without masking the
enhancing lesions. Although this may introduce bias in terms of assessment of
side-based prevalence of vascularity when the vascular asymmetry was near the
cutoff point, it should be noted that the evaluation procedure was similar to
that performed daily in routine clinical practice.
In conclusion, our experience revealed that MDCT made it possible to obtain
high-quality vascular maps of the breast. Breast cancer was found to be
associated with an ipsilateral increased vascularity in a significant
percentage of patients. There was a statistically significant association
between ipsilateral increased vascularity and the prognostic factors of tumor
size, regional lymph node metastasis, cancer stage, nuclear grade, and
histologic grade.
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Abstract
Introduction
