Study population
Patients undergoing NCT and MRI at our institution between November 2010 and February 2014 were retrospectively included,
with the following inclusion criteria: age between 18 and 65 years,
presence of imaging-guided core-biopsy proven Stage II/III operable breast cancer (T > 3 cm) or inoperable locally-advanced breast cancer and unifocal or multiple masses at baseline MRI.
Clinical and pathological features are summarized in Table 1.
This study was conducted in compliance with the ethical regulatory issues of our Institution and patients were asked to provide written informed consent before entering the study.
All patients underwent breast MRI (DWI and DCE-MRI) before and after NCT followed by surgery performed between 14 and 35 days after the completion of NCT.
MRI protocol
Examinations were performed with 1,5 Tesla equipment and 8-channels dedicated phased-array coil and patient in prone position.
Morphological (T2 weighted sequences and DWI on axial plan) and dynamic studies were conducted,
in particular DWI has been acquired with echo-planar single shot axial sequences (TR/TE 11500/72 ms,
matrice 128× 128 pixels,
NEX 16,
FOV (field of view) 30x30 cm e slice thickness 3 mm) and diffusion coefficient applied on three orthogonal planes at 0 e 1500 s/mm² b-value.
Dynamic study was acquired with a gradient echo 4D fat suppressed sequence on axial plan (TR 8 ms,
TE 3,6 ms,
flip angle 10°,
slice thickness 1 mm,
matrix 480x480).
Dynamic study contemplates a pre-contrast sequence and five sequences after intravenous injection of paramagnetic contrast medium (gadobutrol 1,0 mmol/ml); this was administered at a dose of 0,1 mmol/kg,
2 ml/s speed,
followed by 20 ml of saline solution.
Response to NCT
Response was evaluated measuring by electronic calipers at DWI (b value 1500s/mm2) and DCE-MRI (early phase after iv injection of contrast agent) the diameter of malignant lesions and axillary adenopathies before and after NCT.
Breast level
Concerning breast lesions:
- before NCT,
the maximum diameter of each malignant lesions was evaluated.
In the case of multiple cancer only the largest was considered as a target lesions;
- after NCT,
if the lesion faced concentric shrinkage the maximum diameter was measured; if it underwent fragmentation the extent between more distant foci was considered.
For both DWI and DCE-MRI,
Response Evaluation Criteria in Solid Tumors,
RECIST 1.1 were applied for the assessment of NCT response,
defining as complete response (CR) the disappearance of the target lesion; partial response (PR) the diameter of the target lesion decrease more than 30%; stable disease (SD) as non PR non PD; progressive disease (PD) the target lesion increase more than 20% of its diameter.
In addition,
it was also reported the extent of residual disease in terms of one versus >1 breast quadrant involved.
Then multidisciplinary team planned the surgical treatment on the basis of DWI and DCE-MRI respectively (when just 1 quadrant was involved breast conservative surgery-BCS was indicated,
mastectomy was suggested in all the other conditions) and the results were compared with the surgery actually performed.
Figure 1 and 2.
Axillary level
Concerning axillary response,
for each patients:
- before NCT,
the short axis of the largest lymph node was measured;
- after NCT,
the short axis of the same lymph node was considered.
Before and after the treatment,
the measured lymph node was considered negative when short axis diameter was <10 mm and positive when it was >10 mm.
Figure 3.
Pathological lymph node status was considered as the reference standard (positive versus negative).
In particular,
pathological negative status was defined as absence of residual invasive tumor in the lymph nodes while positive in the remaining conditions.
Statistics
Those cases in which DWI correctly planned mastectomy or BCS were defined as true positive and true negative respectively; those planned as mastectomy and then underwent to BCS as false positive,
while those planned as BCS and then underwent to mastectomy as false negative.
Those cases in which DWI correctly or wrongly identified lymph node status were defined as true positive or true negative,
respectively; false positive and false negative were defined those cases in which lymph node status was wrongly evaluated as positive or negative,
respectively.
Sensibility,
specificity and accuracy of DWI in planning breast surgery and in the assessment of axillary NCT response were evaluated.