Iodinated Contrast Enhancement of Breast Cancer on Prone Multidetector Computed Tomography—Preliminary Findings : Journal of Computer Assisted Tomography

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Breast Imaging

Iodinated Contrast Enhancement of Breast Cancer on Prone Multidetector Computed Tomography—Preliminary Findings

Felipe, Vinicius C. MD; Barbosa, Paula N.V.P. MD, PhD; Chojniak, Rubens MD, PhD; Bitencourt, Almir G.V. MD, PhD

Author Information
Journal of Computer Assisted Tomography 47(1):p 45-49, 1/2 2023. | DOI: 10.1097/RCT.0000000000001385
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Abstract

Breast cancer morphologic features are usually evaluated through conventional breast imaging, including full-field digital mammography, digital breast tomosynthesis, and breast ultrasound. However, contrast-enhanced breast imaging has gained increasing importance in the diagnosis and management of breast cancer. Breast magnetic resonance imaging (MRI) and, more recently, contrast-enhanced mammography have allowed an improved assessment of breast tumors, especially in patients with dense breasts, suggesting that both gadolinium and iodinated-based contrast agents can be used to characterize tumor vascularity.1,2

Computed tomography (CT) has always been considered an inaccurate method for breast evaluation; however many studies have shown that conventional chest CT is able to detect malignant breast lesions.3–10 Dedicated CT devices developed for breast assessment, using technologies, such as “cone beam” and “phase contrast,” have shown promising results.11–14 However, only few studies have evaluated the performance of conventional multidetector CT (MDCT) devices in the evaluation of breast lesions (Table 1).15–22

TABLE 1 - Summary of the Main Findings of Prior Studies on MDCT Analysis of Breast Lesions
Author (Year) N Main Result
Nakahara 2002 15 50 3D helical CT can provide good information about the spread of breast cancer and could be an alternative to 3D MRI for preoperative examination of breast cancer.
Inoue 2003 16 149 MDCT can help to distinguish benign lesions from carcinomas and add to the data obtained with mammography or sonography in patients with suspected breast tumors.
Inoue 2005 17 143 MDCT images can assess breast cancer tumor extension highly accurately.
Doihara 2006 18 136 MDCT can provide appropriate information on tumor extent for the determination of adequate surgical margins
Shimauchi 2006 19 69 MDCT is less precise than MRI for evaluating the intraductal component of breast cancer.
Perrone 2008 20 61 Dynamic MDCT can be used in the differentiation of breast lesions suspected on mammography and sonography.
Kimijima 2012 21 74 MDCT is highly effective for detecting DCIS, especially the more aggressive types of DCIS.
Lin 2016 22 97 The addition of the enhancement value (HU) to the MDCT improved the diagnostic accuracy in the differentiation of malignant from benign incidental breast lesions
DCIS, ductal carcinoma in situ

Recently, prone MDCT with dedicated breast protocol has been shown to be feasible and showed substantial agreement with MRI features in breast cancer patients.23 Nonetheless, further studies are necessary to better characterize the behavior of breast cancer on MDCT. The aim of this study was to assess breast cancer enhancement after iodinated contrast administration on prone MDCT.

MATERIALS AND METHODS

Study Design

This retrospective unicentric study was approved by the institutional ethics review board and included patients with newly diagnosed breast cancer who were submitted to breast MRI for locoregional staging and contrast-enhanced MDCT of the chest for systemic staging between March 2019 and July 2021. At our institution, breast MRI is performed for locoregional staging in selected breast cancer patients, at the discretion of the breast surgeon, including high-risk patients, suspected multifocal, multicentric, or bilateral disease, and discrepancy between tumor size at clinical examination and conventional imaging (mammography and ultrasound). Typical indications for chest and abdominal MDCT for systemic staging in breast cancer patients at our institution include clinical stage III for all subtypes or clinical stage II for triple negative or Her2 subtypes. Included patients were submitted to chest CT using a dedicated protocol for breast evaluation, in prone position, using a specially custom-made device (Fig. 1), which reproduces the breast MRI position, with image acquisition before and after nonionic iodinated contrast administration.

F1
FIGURE 1:
Images of the device used to perform chest MDCT on prone position (A) and patient position during the examination (B). Figure 1 can be viewed online in color at www.jcat.org.

MDCT Protocol

Multidetector CT examinations were performed on a 128-channel device, with a 0.5-mm slice thickness, before and after administration of 1 to 2 mL of the nonionic contrast material ioversol (Optiray 320; Mallinckrodt Medical Inc., St. Louis, MI) per kilogram of body weight intravenously with a semiautomated power injector at a rate of 4 mL/s. Chest images acquisition was performed 80 to 90 seconds after the contrast administration (portal venous phase). Multidetector CT images were sent to the Picture Archiving and Communication System for analysis and interpretation, which allows multiplanar, subtracted, and 3D maximum intensity projection reformats.

Image Assessment and Analysis

Breast images in this study were typically assessed using narrow window width (eg, brain window) to improve contrast between enhancing and nonenhancing soft-tissue areas in the breast parenchyma; no computer-aided diagnosis system was used. Two radiologists with 5 and 10 years of experience in breast and cancer imaging reviewed MDCT images after analyzing conventional imaging methods (mammography and ultrasound), histological results from prior percutaneous biopsies, and the breast MRI images. For each patient, a single breast lesion, defined as the dominant lesion (by size) if more than 1 was present, defined here as the “main” or “index” lesion, was classified regarding its imaging phenotype, on both breast MRI, and MDCT, as mass, nonmass enhancement (NME), or both (mass and NME). Mean tumor density (HU, Hounsfield units) of this index lesion was calculated on precontrast and postcontrast CT images, using a 2-dimensional, manually drawn, round or oval region of interest (ROI) covering most of the lesion, avoiding normal fibroglandular parenchyma, adipose tissue, and necrotic areas (Fig. 2). Lesion enhancement on CT was defined as the difference between postcontrast and precontrast tumor density.

F2
FIGURE 2:
Example of ROI placement to measure density before (A) and after (B) iodinated contrast administration on tumor located in the lower outer quadrant of the left breast (2.4 cm index lesion in a multifocal, grade 3, ER/PR+, Her2− NST invasive carcinoma).

MRI Protocol

Breast MRI was performed in a 1.5-T MR imaging system (Achieva; Philips Healthcare, Best, Netherlands; or Magnetom Aera; Siemens Healthcare, Erlangen, Germany) with an 8-channel dedicated breast coil in prone position. A standard dose (0.1 mmol/kg body weight) of gadopentetate dimeglumine (Magnevist; Bayer HealthCare Pharmaceuticals, Wayne, NJ) was injected intravenously as a bolus at 4 mL/s followed by a saline flush. Breast MRI imaging protocol included the following: axial T1 gradient-echo phase, 3-dimensional (3D) imaging; sagittal fat-saturated short tau inversion recovery sequence; axial diffusion-weighted images using spin-echo, single-shot echo planar imaging sequence; dynamic contrast enhancement including 5 axial T1-weighted fat-saturated gradient-echo phases (1 precontrast and 4 postcontrast); and sagittal T1-weighted fat-saturated high-resolution, 3D gradient-echo pulse sequence.

Pathology Assessment

All pathologic results were performed in the institution. According to the fourth edition of the World Health Organization Classification of Breast Tumors, breast malignancies were classified in invasive breast carcinoma of no special type (NST), previously known as invasive ductal carcinoma, and special types invasive breast carcinomas, which includes all other histologic types.24 Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) were obtained from immunohistochemical (IHC) analysis, according to the American Society of Clinical Oncology/College of American Pathologists guidelines.25,26 Tumors were classified based on IHC results in one of the following molecular subtypes: luminal (ER/PR-positive; HER2-negative or positive); HER2 overexpressing (ER/PR-negative and HER2-positive); and triple-negative (ER/PR-negative and HER2-negative).

Statistical Analysis

All statistical analyses were performed using SPSS software, version 20.0 (SPSS Inc., Chicago, IL). Frequencies and percentages were used to describe categorical variables, and mean, standard deviation (SD), and ranges were used to describe continuous variables. Imaging presentation was grouped as mass compared between MDCT and MRI using the Fleiss kappa coefficient (K) with standard error (SE). Agreement was considered poor (K less than 0.19), weak (K between 0.20 and 0.39), moderate (K between 0.40 and 0.59), substantial (K between 0.60 and 0.79), or almost perfect (K higher than 0.80).27 The nonparametric Mann-Whitney test was used to analyze differences in tumor density values and other imaging and pathological tumor features. The significance level was fixed at 5% for all tests.

RESULTS

Sixty breast cancer patients aged between 31 and 74 years (mean, 49.0; SD, 11.6 years) were included. Most patients (n = 50, 83.3%) had NST invasive breast carcinoma and high nuclear grade (n = 48, 80.0%). Most common molecular subtype was luminal (n = 45, 75%), 10 patients (16.7%) were HER-2 overexpressing, and 5 (8.3%) were triple-negative.

At MRI, the index lesion presented as mass in 45 cases (75%), NME in 13 (21.7%) and both mass and NME in 2 (3.3%). Tumor size on MRI ranged from 0.8 to 12.0 cm (mean, 3.7; SD, 2.5 cm), being 14 (23.3%) stage T1 (<2 cm), 33 (55%) T2 (2–5 cm), and 13 (21.7%) T3 (>5 cm). Multifocality and multicentricity were observed in 20 (33.3%) and 18 (30%), respectively. Five tumors (8.3%) showed signs of nipple areola complex invasion, 6 (10%) had skin invasion, and 1 (1.7%) had pectoralis muscle invasion.

All index breast tumors were identified on prone MDCT; 43 cases (70.5%) presented as mass, 13 (21.3%) as NME, and 4 (6.6%) as both mass and NME. Table 2 shows that there was an almost perfect agreement on tumor presentation between MRI and MDCT (K = 0.830). Tumor size on MDCT ranged from 1.0 to 13.0 cm (mean, 3.5, SD, 2.5 cm). Table 3 shows the lesion density on precontrast and postcontrast images. There were no statistically significant differences in tumor enhancement according to histological type, hormonal receptors expression, HER-2 overexpression, subtype, nuclear grade, tumor size, or imaging presentation (Table 4).

TABLE 2 - Comparison Between Type of Enhancement on Prone MDCT and Breast MRI (Kappa = 0.830)
Type of Enhancement on MRI Type of Enhancement on CT Total
Mass NME
Mass 42 (93.3%) 3 (6.7%) 45 (100%)
NME 1 (6.7%) 14 (93.3%) 15 (100%)
Total 43 (71.7%) 17 (28.3%) 60 (100%)

TABLE 3 - Density (HU) of Breast Tumors on Prone MDCT Before and After Contrast Administration, With Images on the Portal Venous Phase
Mean SD Minimum Maximum
Precontrast 37.8 12.0 20 106
Postcontrast 87.9 20.8 53 165
Enhancement 50.2 17.2 20 109

TABLE 4 - Differences in Tumor Density (HU) on Prone MDCT Before and After Contrast Administration, According to Different Pathological and Imaging Findings
Variables Tumor Density (HU) P
N Precontrast Postcontrast Enhancement
Histological type
 NST carcinoma 50 37.3 ± 12.5 86.1 ± 21.1 48.8 ± 17.1 0.204
 Special type carcinomas 10 39.8 ± 9.4 96.9 ± 17.6 57.1 ± 17.0
Hormone receptors
 Positive 45 38.5 ± 13.2 88.0 ± 22.7 49.5 ± 18.9 0.309
 Negative 15 35.4 ± 7.4 87.7 ± 14.7 52.3 ± 11.4
HER-2 overexpression
 Absent 42 36.4 ± 7.8 85.0 ± 17.6 48.6 ± 16.6 0.327
 Present 18 39.6 ± 17.9 93.2 ± 26.4 53.7 ± 19.2
Subtype 0.478
 Luminal 45 38.5 ± 13.2 88.0 ± 22.7 49.5 ± 18.9
 HER2 10 35.2 ± 8.1 84.0 ± 15.5 48.8 ± 11.2
 Triple-negative 5 35.8 ± 6.7 95.0 ± 10.8 59.2 ± 9.0
Nuclear grade
 Low/Intermediate 12 36.3 ± 11.0 83.2 ± 18.5 46.9 ± 13.7 0.567
 High 49 38.1 ± 12.3 89.1 ± 21.4 51.0 ± 18.1
Tumor size at MRI
 < 5 cm 30 37.3 ± 12.8 85.6 ± 21.1 48.2 ± 17.0 0.097
 ≥ 5 cm 30 39.2 ± 9.2 96.4 ± 18.2 57.2 ± 17.1
Tumor presentation at MRI
  Mass 45 37.9 ± 13.0 87.2 ± 21.6 49.4 ± 17.5 0.651
 NME or mass and NME 15 37.3 ± 8.9 89.9 ± 19.1 52.6 ± 16.7

DISCUSSION

In our study, the dominant (by size) “main” or “index” lesion in each patient as noted on MRI was readily identified and showed significant iodinated contrast enhancement on prone MDCT images. The imaging phenotype (defined as being “mass,” “nonmass enhancement,” or a “combination thereof”) of the index lesions for each patient on MDCT had an almost perfect agreement with the phenotype of the same index lesion as identified on breast MRI. No statistically significant difference in quantitative measures of tumor enhancement were seen on CT with regard to tumor histology or other features as seen on pathology (eg, HER-2 overexpression, nuclear grade, etc.).

Several techniques can be used to improve breast evaluation on MDCT. As previously observed on PET-CT studies, prone position provides better characterization of breast lesions and allows direct comparison to breast MRI.23,28,29 The use maximum intensity projection images in multiplanar projections also facilitates detection of breast lesions on chest CT.30 Precontrast images are important to avoid false-positive results related to spontaneously hyperdense lesions, especially hematomas in patients submitted to prior biopsy, which can mimic breast cancer.31,32 Subtracted images can help to identify enhancing masses, however they are not usually necessary in our experience. Dual-energy acquisition have been also suggested, however further studies are still necessary.33,34

Lin et al22 showed that enhancement is a useful tool to differentiate benign and malignant incidental breast lesions on CT. Perrone et al20 showed that dynamic MDCT could also be used in the differential diagnosis of breast lesions on CT, however, it would be necessary to perform multiple image acquisitions, which would increase the radiation dose. Kuroki-Suzuki et al35 analyzed 31 breast cancer patients submitted to MDCT and found that the optimal delay time to depict breast cancer is 80 seconds after contrast injection, regardless of the breast tissue density level. Using the same delay time, which corresponds to the portal venous phase on abdominal CT, all invasive breast carcinomas were identified on prone MDCT in our study, with mean enhancement of 50 HU, ranging from 20 to 109 HU.

In our study, we did not find any statistically significant association between tumor enhancement and pathological or IHC features. Ma et al36 evaluated 240 invasive breast carcinomas with contrast-enhanced cone beam breast CT and compared imaging features with IHC receptors and molecular subtypes. The authors found that HER2-positive cancers mostly manifested as higher density lesions with higher enhancement, whereas triple-negative tumors showed lowest enhancement. In addition, higher enhancement was observed in lesions with low Ki-67 proliferation, and in luminal A subtype, in comparison to luminal B subtype.

This study has several limitations, mainly related to the small sample size, which may have hindered some results and have precluded further quantitative analyses. Most tumors in our sample were stage T2 or T3, because staging chest CT is not routinely performed for stage T1 tumors at our institution; thus, mean tumor size of our sample was larger than the general breast cancer patients' population. Besides, we did not evaluate the presence of ductal carcinoma in situ in this study. Microcalcifications are usually not seen on MDCT because of the method's spatial resolution. However, some authors have shown that intraductal component of breast cancer may present as NME on MDCT, similar to MRI.15,17–19,21

In conclusion, in our limited retrospective review of 60 patients with invasive breast cancer, we found that the index carcinoma usually can be identified and has significant contrast enhancement on prone MDCT images. Besides, there was an almost perfect agreement between MDCT and MRI imaging phenotypes. Thus, future research should focus on using MDCT as an alternative when other contrast-enhanced breast imaging methods (eg, MRI and contrast-enhanced mammography) are not available and should include T1 unifocal breast cancers to see if results are reproducible in smaller lesions. Multidetector computed tomography performed with a specific protocol for breast evaluation could be especially interesting in patients with known invasive breast carcinoma to provide locoregional and systemic staging in a single examination, with no additional radiation.

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Keywords:

breast cancer; computed tomography; contrast media

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