Breast cancer is a diverse group of diseases with different phenotypic and genotypic subtypes. This has significant therapeutic and prognostic effects with the molecular subtyping being an essential therapeutic requirement. Surrogate definitions of the intrinsic molecular subtypes depend upon hormonal receptor status, HER2neu overexpression, and Ki-67 index. This is usually done via immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) [12].
In our study, we correlated the hormonal receptor status, HER2neu expression status, and molecular subtype with imaging features as per mammosonography and MRI.
We found that hormonal-negative tumors were statistically different from hormonal-positive tumors as regards the mass margins, with the hormonal-negative tumors being more circumscribed on mammography, ultrasound, and MRI with a P of 0.03, 0.03, and 0.007 respectively. This was similar to Shin et al. who reported that a circumscribed or microlobulated outline with posterior reinforcement was associated with a high grade and negativity of hormone receptors [13]. Like Song et al. [14], we found no statistically significant difference between hormonal-positive and negative groups as regards the calcification presence, morphology, and distribution. We also found that hormonal-positive tumors were associated with posterior acoustic shadowing in 72.7% of the patients (P = 0.004). This was in concordance to Rashmi et al., where they stated that luminal A and luminal B tumors (HR-positive tumors) had a significant association with non-circumscribed margins and acoustic shadowing (P < 0.0001) [15]. According to this study, we found that hormonal-negative tumors are more likely to show malignant DCE kinetics with washout curves (62.5% of hormonal-negative tumors vs 9.1% of hormonal-positive tumors, P value of < 0.001). Chen et al. reported similar findings, yet this was not statistically significant according to them (P = 0.15) [16]. No statistical significance was found on MRI between hormonal-positive and hormonal-negative tumors as regards the lesion appearance as mass or non-mass enhancement. This was different from Chen et al. results, where they reported that hormonal-negative tumors were more likely to present as non-mass enhancement compared to the hormonal-positive ones (P < 0.005) [16]. There was no significant correlation between internal enhancement patterns and the expression of hormonal receptors. This was in concordance with Tao et al. [17].
In this study, 70% of the HER2/neu-positive tumors had calcifications with only 25.5% of the HER2/neu-negative tumors presenting calcifications (P = 0.007). This goes in concordance with Sun et al. who reported malignant calcification to be more frequent in HER2/neu-positive tumors (P = 0.001) and Boisserie-Lacroix et al. who stated that the presence of calcifications in the mammogram may predict a HER2/neu-positive status when the HER2 score is equivocally 2+ in immunohistochemistry [18, 19].
Elias and colleagues reported that when considering only mass lesions, multifocality was related to increased HER2 overexpression (P < 0.001) [1]. This was similar to what we reported on mammographic examination, where HER2/neu-negative was more likely to be unifocal than HER/2neu-positive tumors (92.5% vs 36.4% respectively) (P < 0.001). No statistical difference between HER2-positive and HER2-negative as regards the DCE kinetics was noted in this study. This was opposite to Elias et al., where an increased chance of HER2 overexpression was noted with washout or fast initial kinetics on DCE-MRI (P = 0.01 and P < 0.01 respectively) [1].
Ko et al. found a significant difference between TNBC and non-TNBC as regard the microcalcifications and the focal asymmetries. They reported that TNBC less frequently had associated microcalcifications (P = 0.0055), while focal asymmetries were more frequent in the TNBC (22%, P = 0.003) [20]. We reported similar findings as regards the less common incidence of microcalcifications in TNBC but not up to a statistically significant level (P = 0.08), yet we did not report any case of asymmetry in the TNBC cases. This difference may be due to the smaller number of cases in our study.
In this study, luminal A, luminal B, and HER2-enriched groups were associated with non-circumscribed margins with luminal A and B tumors presenting posterior acoustic shadowing. This was in concordance to Zhang et al. [21].
In this study, all of the TNBC lesions were masses as seen per mammosonography and MRI. This was different from Dogan et al., as they reported mass lesions in 77.3% of the cases and non-mass enhancement in 22.7% of the cases on MRI and mass lesion in 86% of the cases on US [22]. We also reported that TNBC mass lesions on sonography and MRI were associated with circumscribed margins in 66.7% of the cases. This was different from Dogan et al., where they reported that mass lesions on US had circumscribed margins in 21.1% of the masses [22]. Our findings are similar to Ko et al., where they reported on ultrasound examination that 86% of the TNBC presented as masses and significantly had circumscribed (57%) as opposed to non-circumscribed margins [20].
We also reported a significant difference between TNBC and other molecular subtypes regarding the internal enhancement pattern of mass lesions; rim internal enhancement was predominant in TNBC mass lesions in this study compared to the predominant heterogenous enhancement pattern in the other subtypes. This may be attributed to increased tumoral necrosis in TN breast cancers. Our results were consistent with Azzam et al. and Youk et al., where they reported similar results (P = 0.001 and P < 0.0001, respectively) [23, 24]. Teifke et al. noted that rim enhancement is usually associated with high-grade tumors and is considered the most useful MR imaging feature for identifying TN cancers [25].
The major limitation of this study was a relatively small number of patients. Another limitation is the interobserver variability in reporting the different lesions which is likely to cause some variability in the results reported by different investigators. It is worth noting that possibility of intratumoral heterogeneity especially in the case where the histopathological assessment was via core biopsy may contribute to discordance in ER, PR, and HER2 status, with possible implications for breast cancer subtype classification.