According to the 2013 American College of Radiology BI-RADS lexicon classification of breast density, ACR C indicates that the breasts are heterogeneously dense, which may obscure small mass while ACR D indicates that the breast is extremely dense [10]. Although mammogram is the gold standard technique in the detection and diagnosis of breast cancer, the increased mammographic breast density poses a real challenge in diagnosis owing to the remarkably decreased mammography sensitivity resulting in a considerable number of false-negative mammograms [11,12,13]. On the other hand, the increased breast density may also increase the false-positive mammograms resulting in an unnecessary increase in the recall rates. Adding to this, the increased breast density impacts the risk of breast cancer development being a strong independent risk factor as reported in several studies [14, 15].
In the past few years, the number of breast imaging modalities addressing the problem of the mammography dense breast has increased; thus, the implementation of sound practice has become a real challenge. Out of these new modalities, contrast-enhanced mammography and 3D digital tomosynthesis have gained high appreciation.
In the current study, we compared the performance of contrast mammography, 3D tomosynthesis, and breast ultrasound in the mammographic dense breast. The study included 37 patients with 63 breast lesions assigned as BI-RADS C (34/37, 92%) or BI-RADS D (3/37, 8%).
As regards mammography findings, the commonest presentation was mass lesions (25/63, 40%) followed by breast asymmetry(8/63, 28%). Other lesions included indeterminate calcifications (5/63, 8%) and mass/asymmetry with calcifications (2/63, 3%) while no lesions were identified in 13/63 (21%). Mammography had a sensitivity of 83%, a specificity of 48%, a positive predictive value of 68%, a negative predictive value of 68%, and a diagnostic accuracy of 68%. As reported in several previous studies, evidence suggests that the sensitivity and specificity of mammography are decreased in breasts with a higher density. Chiu et al. [16] reported a sensitivity of 62.8% in the dense breast as compared to 82% in the fatty breast. A drop in specificity was also reported with an increased breast density (89.6% in the dense breast as compared to 96.5% in the fatty breast). The calculated diagnostic indices in our study did not completely match those reported in a cohort study performed by Von Euler-Chelpin et al. [17] on 54,997 participants. In this study, they compared the sensitivity and specificity of mammography as compared to breast density. Although the calculated sensitivity dropped from 80% in the homogeneous fatty breast down to 41% in the dense breast, the specificity of mammography was not significantly changed.
Contrast-enhanced mammography uses a dual-energy technique performed after contrast administration to identify and characterize lesions based on angiogenesis, as well as morphologic features and density [5]. Also, low-energy images of CEM could detect microcalcifications, architectural distortion, and non-enhancing lesions [18].
Kamal et al. [19] analyzed the morphology and enhancement characteristics of breast lesions on CEM. Their retrospective study included 168 consecutive patients with 211 breast lesions. Enhancement was observed in 145/211 lesions (68.7%): 42/145 (29%) benign and 103/145 (71%) malignant lesions (p value ≤ 0.001). They concluded that the morphology and enhancement characteristics of breast lesions on CESM are reliable in differentiating between benign and malignant breast lesions
In the current study, 46/63 (70%) lesions showed contrast uptake. We applied the morphology descriptors to differentiate between benign and malignant lesions with correlation with final pathology, out of which 14/46 (30%) were benign and 32/46 (70%) were malignant, while 17/63 (30%) lesions did not show contrast uptake in CEM, out of which four lesions were malignant upon correlation with final pathology. These four lesions were out of contrast mammographic view as they were very deep on the pectoralis muscle at the axillary tail region.
CEM improves the sensitivity and specificity of mammography because it provides functional information in addition to morphology. So, adding contrast to mammograms in the current study improved the diagnostic indices with a calculated sensitivity of 89%, a specificity of 89%, a positive predictive value of 91%, a negative predictive value of 86%, and a diagnostic accuracy of 89% for CESM.
Our results were comparable to a study performed by Sung et al. [20]; their study included 904 CEM studies for women of high breast cancer risk. They concluded that sensitivity of contrast agent–enhanced mammography was 87.5% (compared with 50.0% for digital mammography) with a specificity of 93.7%.
Sorin et al. [21] performed a retrospective study discussing the role of CEM in women with dense breasts; they stated that CEM may be a valuable supplemental screening modality for women who have dense breasts as it increases the sensitivity of breast cancer detection.
Another study was done by Mori et al. [22] comparing the diagnostic accuracy of CEM to digital mammography in dense breasts. Their study demonstrated a significantly higher sensitivity, specificity, and accuracy of CEM compared to standard mammography.
Initial studies suggest that, when tomosynthesis is used in conjunction with standard 2-dimensional digital mammography as a screening test, DBT can reduce recall rates and increase cancer detection rates [23].
The main advantage of tomosynthesis is its ability to diminish the masking effect of tissue overlap and structure noise usually encountered with 2D mammography [24].
In our study, tomosynthesis had a sensitivity of 86%, a specificity of 81%, a positive predictive value of 86%, a negative predictive value of 81%, and a diagnostic accuracy of 84%.
Our results were comparable with Bian et al. [25] and Asbeutah et al. [26] where they also found that DBT showed increased sensitivity and specificity compared to mammography in dense breasts.
Phi et al. [27] performed a meta-analysis on DBT in dense breasts for screening or diagnosis. They concluded that DBT increased cancer detection rate in screening and diagnosis; in diagnosis, DBT increased sensitivity but not specificity.
In 2016, Rafferty et al. [28] performed a study including 452,320 examinations: 278,906 were digital mammography alone and 173,414 digital mammographies plus tomosynthesis. They concluded that adding DBT to digital mammography increased the cancer detection rate more in women with heterogeneously dense breasts than in those with either non-dense breasts or extremely dense breasts. The reduction in recall rate was also greatest in the heterogeneously dense subgroup.
Skaane et al. [29] conducted a prospective study on DM versus DBT and DM in screening. They found that the addition of digital breast tomosynthesis to digital mammography resulted in significant gains in sensitivity and specificity.
Breast ultrasound had been used for many years in the characterization of breast lesions. The J-start prospective randomized control study of ultrasonography has shown increase sensitivity and detection rates of early cancers [30].
In our study, breast ultrasound had a sensitivity of 97%, a specificity of 85%, a positive predictive value of 90%, a negative predictive value of 96%, and a diagnostic accuracy of 92%.
Our results matched with Nandan et al. [31], a retrospective study that focused on charts from the Cancer Institute of Guyana to assess the role of ultrasound in screening young women. They concluded that ultrasonography is effective and sensitive in the diagnosis of breast cancer. It is also effective in diagnosing benign breast diseases in younger women with dense breast tissue.
This study had few limitations such as the interpretation of images was done by a single radiologist and the absence of an appropriate BI-RADS lexicon for CEM examination. A standardized lexicon of morphology descriptors seen on CEM would provide the optimal analysis and reporting of enhancing lesions detected in the breast.
