Breast Clinical Reviews

Breast Cancer Research and Treatment 92: 51–60.

Purpose. To investigate the safety, efficacy and feasibility of using high-intensity focused ultrasound (HIFU) as a non-invasive treatment for patients with breast cancer. Patients and Methods. Twenty-two patients with breast cancer were enrolled into this non-randomized prospective trial. Disease TNM stage was classified as stage I in 4 patients, stage IIA in 9 patients, stage IIB in 8 patients, and stage IV in 1 patient. Tumor size ranged from 2 to 4.8 cm in diameter (mean 3.4 cm). All patients received chemotherapy, radiation and tamoxifen, following HIFU for the primary lesions. Outcome measures included radiological and pathologic assessment of the treated tumor, cosmesis, and local recurrence. A cumulative survival rate is calculated by using the Kaplan Meier method. Results. No severe complications were encountered after HIFU. Post-operative imaging demonstrated positive response and regression of all treated lesions. Follow-up biopsy revealed coagulation necrosis of target tumor and subsequent replacement by fibroblastic tissue. After a median follow-up of 54.8 months, 1 patient died, 1 was lost to follow-up, and 20 were still alive. Two of 22 patients developed local recurrence. Five-year disease-free survival and recurrence-free survival were 95% and 89%, respectively. Cosmetic result was judged as good to excellent in 94% of patients. Conclusions. HIFU treatment is safe, effective, and feasible for patients with breast cancer. But, large-scale, multiple-center clinical trials will be needed to determine the future role of this novel modality.

Br J Cancer 89(12): 2227-33.

High-intensity focused ultrasound (HIFU) is a noninvasive treatment that induces complete coagulative necrosis of a tumour at depth through the intact skin. This study was to explore the possibility of using HIFU for the treatment of patients with localised breast cancer in a controlled clinical trial. A total of 48 women with biopsy-proven breast cancer (T(1-2), N(0-2), M0) were randomised to the control group in which modified radical mastectomy was performed, and the HIFU group in which an extracorporeal HIFU ablation of breast cancer was followed by modified radical mastectomy. Short-term follow-up, pathologic and immunohistochemical stains were performed to assess the therapeutic effects on tumour and complications of HIFU. The results showed that no severe side effect was observed in the HIFU-treated patients. Pathologic findings revealed that HIFU-treated tumour cells underwent complete coagulative necrosis, and tumour vascular vessels were severely damaged. Immunohistochemical staining showed that no expression of PCNA, MMP-9, and CD44v6 was detected within the treated tumour cells in the HIFU group, indicating that the treated tumour cells lost the abilities of proliferation, invasion, and metastasis. It is concluded that, as a noninvasive therapy, HIFU could be effective, safe, and feasible in the extracorporeal treatment of localised breast cancer.

Ultrasound Med Biol 29(10): 1487-92.

Proliferation, invasion, immortalization and metastasis are the main malignant characteristics of cancer. Previous studies have shown that high-intensity focused ultrasound (US), or HIFU, can induce irreversible damage both to breast cancer cells and to tumor blood vessels. However, light microscopy alone may not always show this clearly. In this study, molecular biologic techniques were used to examine any changes in molecular markers associated with malignant behavior after exposure to HIFU. A total of 48 women with breast cancer were randomized to a control group (mastectomy) and a HIFU group (HIFU followed by mastectomy). Immunohistochemical staining, messenger RNA (mRNA) in situ hybridization and telomere-repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA) techniques were used to detect tumor expression of proliferating cell nuclear antigen (PCNA), cell adhesion molecule CD44v6, matrix metalloproteinase-9 (MMP-9), erbB2 mRNA, and to measure telomerase activity in both groups. The results demonstrated that there were significant alterations in expression of PCNA, CD44v6, MMP-9, erbB2 mRNA, and a dramatic decrease in telomerase activity in the HIFU group. It is concluded that malignant tumor characteristics are arrested by HIFU, and that biologic factors are potential markers for assessing HIFU efficacy.

Breast Cancer Res Treat; 82(2):93-101.

PURPOSE: To assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters to monitor residual tumor following non-invasive MRI-guided focused ultrasound surgery (MRIgFUS) of breast tumors. METHODS: DCE-MRI data were acquired before and after the MRIgFUS treatment of small breast tumors (d < 3.5 cm) for 17 patients. The lesion was surgically resected and the presence of residual tumor was determined by histopathological analysis. The percentage of residual tumor was correlated with three DCE-MRI parameters measured at the maximally enhancing site of each tumor: increase in signal intensity (ISI), maximum difference function (MDF) and positive enhancement integral (PEI). RESULTS: A good correlation was found between the ISI (r = 0.897), MDF (r = 0.789) and PEI (r = 0.859) parameters and the percentage of residual viable tumor determined by histopathology. A receiver operator characteristic curve analysis yielded a cutoff value for ISI at 20% with a sensitivity of 77% and a specificity of 100%. CONCLUSION: These results suggest that parameters from DCE-MRI data could provide a reliable non-invasive method for assessing residual tumor following MRIgFUS treatment of breast tumors.

Radiology 227(3): 849-55.

PURPOSE: To evaluate the effectiveness of noninvasive magnetic resonance (MR) imaging-guided focused ultrasonographic (US) ablation of breast carcinomas. MATERIALS AND METHODS: Before undergoing tumor resection, 12 patients with invasive breast carcinomas were treated with MR imaging-guided focused US ablation consisting of multiple sonications of targeted points that were monitored with temperature-sensitive MR imaging. The patients were treated with either one of two focused US systems. The effectiveness of the treatment was determined at histopathologic analysis of the resected mass that was performed to determine the volumes of necrosed and residual tumor. Complications resulting from the procedure were assessed by means of questionnaires, medical examinations, and MR image analysis. RESULTS: US ablation was well tolerated by the patients, and with the exception of minor skin burns in two patients, no complications occurred. Histopathologic analysis of resected tumor sections enabled quantification of the amount of necrosed and residual tumor and visualization of the surrounding hemorrhage. In three patients treated with one of the US systems, a mean of 46.7% of the tumor was within the targeted zone and a mean of 43.3% of the cancer tissue was necrosed. In nine patients treated with the other US system, a mean of 95.6% of the tumor was within the targeted zone and a mean of 88.3% of the cancer tissue was necrosed. Residual tumor was identified predominantly at the periphery of the tumor mass; this indicated the need to increase the total targeted area (ie, with an increased number of sonications). CONCLUSION: Thermal coagulation of small breast tumors by means of MR imaging-guided focused US appears to be a promising noninvasive ablation procedure.

Radiology 219(1): 176-185.

PURPOSE: To test the feasibility of noninvasive magnetic resonance (MR) imaging-guided focused ultrasound surgery (FUS) of benign fibroadenomas in the breast. MATERIALS AND METHODS: Eleven fibroadenomas in nine patients under local anesthesia were treated with MR imaging-guided FUS. Based on a T2-weighted definition of target volumes, sequential sonications were delivered to treat the entire target. Temperature-sensitive phase-difference-based MR imaging was performed during each sonication to monitor focus localization and tissue temperature changes. After the procedure, T2-weighted and contrast material-enhanced T1-weighted MR imaging were performed to evaluate immediate and long-term effects. RESULTS: Thermal imaging sequences were improved over the treatment period, with 82% (279 of 342) of the hot spots visible in the last seven treatments. The MR imager was used to measure temperature elevation (12.8 degrees -49.9 degrees C) from these treatments. Eight of the 11 lesions treated demonstrated complete or partial lack of contrast material uptake on posttherapy T1-weighted images. Three lesions showed no marked decrease of contrast material uptake. This lack of effective treatment was most likely due to a lower acoustic power and/or patient movement that caused misregistration. No adverse effects were detected, except for one case of transient edema in the pectoralis muscle 2 days after therapy. CONCLUSION: MR imaging-guided FUS can be performed to noninvasively coagulate benign breast fibroadenomas.