1434 Fig. 3 Schematic diagram demonstrating breast cancer patient in prone position and MRI-guided focussed ultrasound equipment treatment of a malignant breast tumour by Huber and colleagues [40]. In this feasibility study a patient with a core biopsy-proven invasive breast cancer was treated with MRI-guided FUS 5 days prior to breast-conserving surgery. Analysis of the breast tissue specimen revealed areas of lethal and sublethal tumour damage, but no exact percentage was provided. After these initial studies, Gianfelice and colleagues were the first to report on the accuracy of MRI-guided FUS for treatment of breast cancer patients, according to a treat-and-resect protocol. In their initial study 12 patients with invasive breast cancer were treated with MRI-guided FUS prior to surgery [41]. Histopathologic analysis of resected tumour in nine patients treated with the newest MRI-guided FUS system showed that a mean of 88.3% cancer tissue was necrosed. Residual tumour was in all cases observed at the periphery of the tumour mass, indicating the need for larger (>5 mm) safety margins around the MRI visible tumour. These results were further supported by findings of the same group in 17 patients with invasive breast cancer that were treated with MRI-guided FUS prior to surgery [42]. Complete (100%) necrosis (Fig. 4) or less than 10% residual tumour was observed in 13/17 (76%) lesions. This study also provided evidence than contrast-enhanced MRI was a reliable method to predict the presence of residual tumour after MRI-guided FUS procedure. In agreement with these findings, Zippel et al. reported the results of a phase 1 trial on MRI-guided FUS ablation of breast cancer, with use of the same ExAblate 2000 system [43]. They treated ten patients 1 week prior to lumpectomy and reported a range of results with complete necrosis in only two patients (20%). Based on this result, it was concluded that there are still several issues that need to be resolved before MRI-guided FUS can become a standard therapeutic technique for breast cancer treatment. They reported that the precision of the focussed sound waves needs to be perfected to destroy 100% of tumour tissue within the lesion, as is achieved with breast-conserving surgery. Secondly, as a surgeon attempts to remove a margin of healthy tissue around the lesion to ensure negative margins, they proposed that it may be necessary to increase the outer limits of the MRI-guided FUS treatment zone to ensure complete eradication of microscopic tumour foci. In the study performed by Khiat et al. the effect of post- treatment delay for evaluation of MR images on the presence of residual cancer was assessed in 25 patients with 26 tumours [44]. Histopathological analyses following MRI-gFUS showed no residual cancer in 8 lesions (31%), less than 10% in 11 lesions (42%) and between 20–90% in 7 lesions (27%). They recommend an interval of approximately 7 days to determine the effectiveness of MRIgFUS, due to the fact that some benign processes, such as oedema, fibrosis, necrosis, and inflammation, can mimic for a malignant process in that period. More recently, Furusawa et al. published improved results of MRI-guided FUS for tumour ablation in a group of 30 breast cancer patients [45]. All patients underwent surgery after FUS ablation. On pathologic examination the mean percentage of tumour necrosis was 97% of tumour volume. Fifteen patients (50%) had 100% necrosis of the ablated tumour. The first study on MRI-guided FUS ablation of breast cancer as an adjunct to a preexisting tamoxifen citrate Fig. 4 Excised breast tissue specimen after MRI-guided focussed ultrasound ablation of a breast cancer, margins delineated with black arrows