BC is a heterogeneous disease, with distinct molecular subtypes which have both prognostic and predictive value. In this context, precision medicine involves the use of biomarkers to create customised treatments. Furthermore, the possibility to draw a reliable correlation between molecular subtypes and imaging features of BC is envisaged to improve patients’ care. As a consequence, nowadays, imaging aims to offer a complementary, noninvasive method to obtain biological information about BC, in addition to traditional tissue-sampling-derived biomarkers.
Breast MRI is considered the more promising technique to differentiate tumour subtypes noninvasively [6, 16]. Contrast-enhanced sequences are the backbone of any breast MRI protocol, providing information about morphological and kinetic features of BC. To overcome the suboptimal specificity of contrast-enhanced MRI, functional techniques, such as MR spectroscopy and DWI, have been widely investigated and progressively introduced into routine clinical practice. Nowadays, a basic mpMRI protocol includes unenhanced sequences (T2 weighted and DWI) followed by the series of pre- and post-contrast T1-weighted acquisitions [13], since it was demonstrated that mpMRI including contrast-enhanced sequences and DWI increases diagnostic accuracy in BC diagnosis [16, 24]. Also, magnetic resonance spectroscopy improves the diagnostic accuracy of breast MRI [25,26,27,28,29]; however, technical challenges and operator dependency have limited large-scale implementation of this technique [30].
The purpose of our study was to clarify whether diagnostic mpMRI at 3 T could be a reliable noninvasive predictor of histological tumour type and molecular subtype of BC. Most of the patients included in this study (78.2%) were affected by invasive carcinoma NST, which is the most common type of BC, 12% by ILC, and about 10% by DCIS. Our distribution substantially reflected data reported in literature [31,32,33,34,35].
The specific features of DCIS are calcifications at digital mammography (70–90% of cases [36]) and non-mass enhancement at MRI contrast-enhanced sequences (up to 81% of cases [34, 37,38,39]); our results (86.7% of DCIS presented as non-mass enhancements, p < 0.001) are in substantial agreement with those data. A second MRI feature significantly associated with DCIS was T2 isointensity (78.6%, p < 0.001) (Fig. 1), also in agreement with data reported in literature too [39]. DCIS was significantly associated with the absence of axillary adenopathy (0%, p = 0.003); this result was expected, since DCIS is confined to the mammary ductal lobular system, without invasion of the basement membrane. However, the occurrence of lymph node metastases is still possible (likely due to missing areas of microinvasion in large-sized tumours or iatrogenic dissemination of tumour cells during preoperative breast biopsy [36]).
The term invasive carcinoma NST identifies a subset of invasive BCs that cannot be classified morphologically as any of the special histological types. ILC, instead, is characterised by a typical discohesive morphology and by the loss of E-cadherin function. The small cohort of ILC included in the study (although reflecting data in literature [31,32,33]) could explain the lack of statistical significance of our results. On the contrary, MRI features significantly associated with invasive carcinomas NST were as follows: mass enhancement, intralesional necrosis and abnormal axillary lymph nodes. The majority of invasive BCs appear as masses with intermediate to low signal intensity on T2-weighted images, due to high cellularity and low water content [13]; our results are in line with these findings. The contemporary association between invasive BC of NST and intralesional necrosis (that shows high signal on T2-weighted images by definition [7]) can be explained by the fact that the evaluation of T2-signal intensity in this study was based on the predominant signal intensity of each lesion; therefore, lesions with only small areas of intralesional necrosis were still classified as isointense or hypointense.
As expected, rim enhancement, intralesional necrosis, peritumoural oedema and the presence of metastatic axillary lymph nodes were predictors of G3 status. These results emphasise the evidence that poorly differentiated, aggressive BCs are associated with poor prognostic indicators at breast MRI. Moreover, we showed an inverse correlation between tumour grading and ADC values, since very low ADC values were significantly associated with high tumour grades. This result has confirmed the predicting value of DWI regarding nuclear grading, as suggested by a few previous studies [10, 11, 17].
The vast majority of invasive breast lesions included in this study were luminal-like (70.2%), while triple-negative and HER2-positive cases represented a minority of the sample (26.2% and 3.6%, respectively). These data reflect the lower frequency of these molecular subtypes and are comparable to similar series in literature [40, 41]. In this study, luminal-like and HER2-positive BCs were more frequently characterised by irregular shape. In particular, most luminal A-like were irregular-shaped (42.9%) masses (77.8%), with non-circumscribed margins (94.3%) and without rim enhancement (91.4%).
Furthermore, our study has demonstrated that the absence of MRI features on T2-weighted images associated with poor prognosis, such as intralesional necrosis [42] and peritumoural oedema [43, 44], was significantly associated with luminal A-like tumours (Fig. 3). In particular, the absence of peritumoural oedema resulted independently associated with the luminal A-like status, in agreement with previous studies [8, 10, 45]. Finally, luminal A-like tumours in our study were significantly associated with the absence of axillary adenopathy, confirming that this BC subtype is characterised by a less aggressive behaviour and a better prognosis [46].
Triple negative BCs are biologically and clinically aggressive tumours with peculiar imaging features, on both conventional breast imaging (frequently mimicking benign lesions [47,48,49]) and MRI. In our study, triple negative BCs were predominantly masses (81.1%), characterised by round shape (86.7%), non-circumscribed margins (90%) and rim enhancement (73.3%). Round shape and rim enhancement were independently associated with the triple-negative status (Fig. 4). These data confirm existing evidence in literature [7, 9, 10, 45, 50,51,52,53,54]. The typical regular shape can be explained by the frequent occurrence of “pushing”, non-infiltrative growth pattern of triple negatives compared to other subtypes of BC, while the presence of rim enhancement on contrast-enhanced sequences has been associated with increased angiogenesis and vascular endothelial growth factor expression and with the lack of oestrogen and progesterone receptors [55, 56]. Among MRI features on T2-weighted images, intralesional necrosis and peritumoural oedema have proved to be positive predictor of the triple-negative status. These results are in accordance with previous literature [7, 8, 10, 45, 50, 53].
Our study has some limitations. First, it was a single-centre, retrospective study, and the cohort of patients enrolled was relatively small, and the number of triple-negative and HER2-positive BCs was even smaller, because those patients tend to receive neoadjuvant chemotherapy. Secondly, MRI datasets were evaluated by two readers, in consensus, not considering interobserver variability. In addition, due to technical problems, percutaneous biopsies under mammographic guidance were not performed during the enrolment period, and this could have caused an underestimation of the number of DCIS cases. Finally, molecular subtypes were determined using immunohistochemical surrogates, which lack in standardisation compared to gene profiling, even if they have shown similar clinical significance and are nowadays routinely used [4].
In conclusion, we showed that mpMRI at 3-T MRI has proved to be a valid noninvasive tool to distinguish between BC subtypes, especially luminal A-like and triple negative, even though histopathology remains the standard of care also in the present time of rapid development of advanced breast imaging.
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