Breast cancer is the most common cancer among females, and a substantial reason for women misery and precocious death. It is estimated that 2.3 million new patients are diagnosed with breast cancer annually all over the world [13, 14].
The asymmetry is a mammographic area of increased breast density compared to the corresponding area in the contralateral breast. Most asymmetries are benign or because of summation artifacts due to superimposition of breast tissue during mammography, but an asymmetry may suggest breast cancer. Estimation and diagnosis of asymmetries are challenging as they often are superfine and mimic typical fibro glandular tissue [15].
Contrast-enhanced mammography has a superiority in explaining both anatomic changes and local perfusion changes caused by tumor angiogenesis [17].
CEM is beneficial in settling vague findings detected at conventional breast imaging, preoperative staging of breast cancer to assess the extent of disease, detection of tumor multiplicity, and assessment of treatment response. It is used as an alternative to breast MRI in women who are at an increased risk of developing breast cancer. Also, it may detect ductal carcinoma in situ (DCIS); mostly associated with microcalcification detected in low-dose images [16, 17].
The aim of this work is to evaluate the diagnostic role of CEM in the differentiation between benign and malignant breast architectural asymmetries detected on mammograms.
This study included 513 females’ patients presented with 540 indeterminate and suspicious asymmetries. The age of the patients ranged from 19 to 73 years, with a median age of 47 years and a mean age of 47.9 years ± 9.09.
In this study, symptomatic cases were 403/513 (78.5%) and the most common clinical presentation was breast mass 217/513 (42.3%). There was a significant correlation between symptoms and malignancy (P < 0.001). Breast mass presentation was more in malignant cases, out of 395 pathologically proven malignant asymmetry, 201 cases presented with breast mass complaint (201/395) 50.8%.
In keeping with this study, Tennant et al. [18] stated that CEM supplies immediate and clinically useful information in patients with suspicious palpable abnormalities.
The breast density was classified according to the American College of Radiology Breast Imaging-Reporting and Data System (ACR-BI-RADS) lexicon into ACR A, B, C and D. In this study, there was no significant correlation between breast density and malignant pathology with p value = 0.156. This disagrees with Gordon, 2021[19] who realized that dense breast tissue is an independent risk factor for developing cancer.
CEM has several indications in this study; most cases 65% had performed it for better assessment of abnormal imaging findings on sonomammography to set diagnosis (benign, malignant nor no abnormal underlying findings), 35% of them had performed it to evaluate disease extent and staging as regards size, multiplicity and bilaterality. CEM added extension in 118/540 (21.8%) as follows: added wider extension in 91 cases, additional enhancing lesion in contralateral breast in 20 case and additional enhancing lesions in the same breast (multifocal/multicentric) in seven cases.
Regarding histopathological diagnosis of the 97 benign lesions (17.9%) included in the study, 6.9% were mammary adenosis, 3.7% were mastitis, 2% were fibrocystic disease, 0.6% were fat necrosis and 4.8% were other benign lesions.
Regarding histopathological diagnosis of the 395 malignant lesions (73%) included in the study, 57.8% were IDC, 7% were ILC, 3.3% were DCIS, 2.6% were IDC with DCIS, 1.5% were invasive mixed carcinoma and 0.9% were other malignant lesions. Kamal et al. [20] goes with this study who reported that according to histopathology results and outcomes of follow-up studies, 35/380 (9.2%) asymmetries were overlapping tissues, 88/380 (23.2%) were benign lesions, and 257/380 (67.6%) were malignant lesions.
Focal asymmetry was the most prevalent asymmetrical density in the present study (356/540) 65.9%. Harvey et al. [21] considered focal asymmetry more suspicious than global asymmetry, especially if accompanied with parenchymal distortion. In fact, most of our focal asymmetry cases were malignant (269/356) 75.6%, especially in instances when the focal asymmetry was associated with suspicious mammographic findings like distortion, pathological axillary lymph nodes, suspicious calcifications, skin, and nipple changes (97/269) 36% (P value < 0.001).
On the contrary, focal asymmetry cases were more likely to be associated with a benign pathology if they did not present with other suspicious findings (16/269) 6%.
In this study, all non-enhancing focal asymmetries were benign. Most of the patients in the study with malignant focal asymmetry showed mass enhancement 171 case, 86 malignant cases of focal asymmetry showed non-mass enhancement, the extension and size of those non-mass enhancement were better delineated by CEM when compared to sonomammography, this agrees with Wessam et al. [22] that stated that focal and global asymmetries associated with other suspicious mammographic findings were statistically significant with malignancy and CEM played a great role in delineation of tumor size and extension. Any non-enhancing asymmetries of benign nature have no associated suspicious imaging findings.
Global asymmetry was the second most frequently represented asymmetrical density in this study (157/540) 29%; if it was not associated with other mammographic suspicious findings, it was statistically correlated with benign findings; this agrees with Youk et al. [4]; they found that global asymmetry is almost benign and needs no additional evaluation if there are no corresponding palpable abnormalities, architectural distortions, significant calcifications, or masses (BI-RADS Category 2).
Single view asymmetry was the third most frequently represented asymmetrical density in our study (21/540) 3.9%, ten cases of single view asymmetry (47.6%) were malignant, four cases (19%) were benign, and seven cases were normal (33%) with no underlying pathology. This matches with the result of the study of Kamal et al. [20] who found that 45% of one view asymmetry were malignant, 20% were benign and 35% were normal.
A developing asymmetry should be viewed with suspicion because it is an uncommon manifestation of breast cancer [4]. It was the least asymmetry represented in this study (6/540) 1.1%. Six cases were pathologically proven to be malignant; three cases were invasive ductal carcinoma and the other three were invasive lobular carcinoma. Chesebro et al. [23] reported that the growth pattern of ILC makes it represent a high percentage of developing asymmetries.
In terms of lesion detection in this study, 324/513 (63.2%) were heterogeneously dense breasts and extremely dense breast, which are the main causes of false-negative and false-positive cases in mammography. Adding contrast mammography provides additional information in dense breasts as underlying lesion enhancement, extension, and multiplicity. The heterogeneous dense parenchyma did not correlate with a corresponding degree of background parenchymal enhancement (BPE). In keeping with this study, several studies including Fallenberg et al. [24], Cheung et al. [25], Dromain et al. [26] proved that CEM is superior to mammography in the identification of multiplicity, extent, and size of malignant lesions especially in the dense breast parenchyma.
The commonest causes of false-positive asymmetries in this study are the inflammatory breast lesions (13/33, 39.4%). Wessam et al. [22] found that inflammatory breast lesions are the commonest cause of false-positive asymmetries in their study (8/15, 53.3%).
When compared to sonomammography, CEM showed higher sensitivity (96.5% vs. 85.8), specificity (77.1% vs. 64.4%), NPV (88.8% vs. 62.7%), PPV (92.04% vs. 86.7%) and accuracy (91.3% vs. 80%). Our study agrees with Kamal et al. [20] who compared CEM and sonomammography in terms of accuracy (88.4% vs. 80.53%).
Wessam et al. [22] reported CEM sensitivity of 100% (vs. 97.8% for sonomammography), and positive and negative predictive values of 85.85 and 100% (vs. 93.7 and 93% for sonomammography, respectively). Dromain et al. [26] also proved that CEM had better sensitivity than FFDM plus US (93% versus 90%), as well as better specificity (63% versus 47%). The study of Tardivel et al. [27] concluded that the high NPV of CEM was valuable in resolving cases with indeterminate lesions (i.e., BI-RADS 3 or 4a) by averting the need for biopsy.
The main limitation in using CEM is the shortage in availability of biopsy capability [27]. If a finding is found on recombined images only, it can be sampled by finding either a low-energy correlate to target with stereotactic/tomosynthesis-guided core biopsy, an ultrasound correlates to target for ultrasound-guided biopsy, or an MRI correlate to target for MRI-guided biopsy [28]. If no mammographic or ultrasound correlate is seen, CEM may result in diagnostic MRI examinations for these patients [27].
Like conventional mammography, areas along the chest wall, far medial breast, or in the axilla may be a cause for a false-negative study as they may not be well-imaged. This can be avoided by performing breast MRI for better assessment [27].
Radiation exposure is another disadvantage of CEM in comparison with FFDM because the average glandular dose of CEM is typically 1.2–1.5 times greater than that of FFDM [24]. Also, CEM has a risk for contrast reaction and the diagnosis of inflammatory breast lesions is challenging due the similarity of enhancement patterns between malignant and inflammatory lesions [29].
Our study was limited by the fact that cases deemed to be benign or negative on histopathology did not undergo follow-up period to determine the true negative disease status.
