Currently, neoadjuvant chemotherapy (NACT) is widely used as first of multidisciplinary management of breast cancer without distant metastases [16, 17, 18, 19]. Besides reducing the tumour mass and thereby offering better conditions for local treatment (BCT – breast conserving therapy), NACT provides professionals with unique opportunities for in vivo chemotherapeutic evaluation of cancer cells’ sensitivity and for the quest of new biomarkers of therapeutic response, and – in the event of poor response and progression of the disease – it offers a chance to alter the treatment scheme or refer a given patient for surgical treatment [20, 21]. Apart from the predictive and prognostic factors known to date, including staging, grading, HER2 status, hormone receptors status, and Ki 67%, the therapeutic response of the tumour to NACT provides information about the patient’s prognosis. Obtaining complete pathological response (pCR) defined as ypT0/Tis, ypN0 translates into better EFS and OS [22, 23, 24, 25, 26]. This served as the basis for the US Food and Drug Administration in July 2020 to accept pCR as the final point of clinical studies in the neoadjuvant therapy of early breast cancer with a high recurrence risk . Evaluating the tumour response to NACT is key to planning further therapy.
To the best of our knowledge, our study is one of the few attempts to evaluate the efficiency of CESM in determining the CR of breast cancer following NACT and the only one to compare the efficiency of CESM with conventional MMG.
The precision of treatment evaluation on MMG depends on the breast structure and morphology of the infiltration itself. The efficiency of evaluation upon MMG, similarly to physical examination, decreases if the tumour is a spiculated or an irregularly limited mass, and the breast has a glandular structure, which may cause the full image of the tumours to be masked by the glandular tissue . The presence of microcalcifications does not correlate with the post-NACT tumour size, as their presence and image may result from tumour necrosis. Earlier studies revealed that even as much as 44% of microcalcifications presence after breast cancer treatment does not correlate with the presence of malignancy .
In a Swedish retrospective study, Skarping et al. demonstrated that, in the majority of patients, the breast density on mammography decreased during NACT. However, this value was not a direct predictor of pCR for the treatment applied, which confirms the insufficiency of standard mammography for evaluating post-NACT residual lesions (29).
In our study, nearly half of the subjects had a highly glandular or glandular/adipose breast tissue structure, and 20.63% of cases (13/63) demonstrated multifocal lesions. The arguments above account for such a low sensitivity of MMG in detecting CR – 33.33%.
Contrast-enhanced spectral mammography provides a double amount of information:
morphological information (as in standard mammography) – in low-energy images;
functional information – in subtraction images that visualise the vascularisation of breast lesions.
CESM is characterised by very high sensitivity in detecting focal breast lesions, and the tumour size on CESM correlate well with histopathological examination in non-NACT patients [30, 31].
In our study, the sensitivity of CESM in a group of NACT patients was 85.71%, its specificity – 71.42%, the PPV – 60%, and the NPV – 90.90%. In the assessment of the prognostic factor, i.e. CR following NACT, CESM reaches significantly higher sensitivity than MMG, but unfortunately its specificity is much lower. Similar values, especially in the assessment of specificity, were obtained by Patel et al. (sensitivity: 95%, specificity: 66.7%, PPV: 55.9%, NPV: 96.7%) and by Iotti et. al. (sensitivity: 100%, specificity 84%, PPV 57%, and NPV 100%) [32, 33]. These results demonstrate that imaging techniques, even after intravenous administration of a contrast agent, do not allow for differentiation between residual infiltration lesions and co-existing inflammatory/reactive lesions.
In our study, the largest pretreatment tumour dimensions on MMG and CESM were similar and there is essential difference between these modalities (R = 0.89, p < 0.01). However, these differences become significant following neoadjuvant chemotherapy (R = 0.55, p < 0.01).This is due to the fact that post-NACT tumours reduce their density and then become difficult to be distinguished from a glandular tissue based on morphological images alone. On the other hand, the functional information provided by CESM on subtraction images, the residual infiltration is clearly visible, and the type of breast tissue does not affect its visualisation.
Our study showed that standard MMG has a tendency to overestimate the dimensions of residual lesions following NACT, while CESM tends to underestimate them. Different results were obtained by Łuczyńska et al., were CESM overestimated the results by 1.7 mm . However, this difference may arise out of the fact that Łuczyńska analysed tumours prior to treatment, while our analysis concerned tumours following NACT, which caused damage to the tumour’s vessels and, as a consequence, could account for the underestimation of results. The study by Iotti et al., which was focused on NACT female patients, revealed that CESM tends to underestimate the dimension of residual lesions by 4.1 mm, which is comparable to our results . It must also be emphasised that the underestimation of the dimensions of residual lesions in our study has no impact on the scope of surgical treatment. Since CESM is a method involving vascularisation of the tumour focus, the effect of excessive reduction in vascularisation around the tumour during NACT may account for the weaker enhancement of the residual tumour mass on follow-up CESM, and thereby underestimating the actual dimension of residual lesions. A similar problem concerns MRI, which also tends to underestimate residual lesions in follow-up examinations [32, 35].
The sensitivity of CESM in detecting breast cancer is comparable to that of MRI, with the former modality being cheaper, as well as quicker to perform and interpret. In the group of NACT patients, CESM significantly outperforms standard mammography in evaluating residual lesions following NACT.
A limitation of our study is the small number of participants, which results from the national qualification guidelines for female patients supposed to receive NACT. However, the initial results are encouraging enough to continue this study with more subjects.