Ablation Of Breast Cancer Research Articles

Increased infiltration of activated tumor-infiltrating lymphocytes after high intensity focused ultrasound ablation of human breast cancer

Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can induce a distinct inflammatory reaction with marked infiltration of lymphocytes after direct tumor destruction. In this study, we investigated the status of tumor-infiltrating lymphocytes (TILs) after HIFU ablation of human breast cancer and explored mechanisms that may be involved in HIFU-triggered, antitumor immune response. A total of 48 female patients with biopsy-proven breast cancer were divided randomly into 1 of 2 groups: control group (n = 25), in which only modified radical mastectomy was performed, or HIFU group (n = 23), in which HIFU ablation of the primary breast cancer was performed prior to modified radical mastectomy. Using semiquantitative immunohistochemical analysis, tumor-infiltrating T lymphocytes and subsets, B lymphocytes, and natural killer (NK) cells were assessed in all patients. Expression of Fas ligand (FasL), granzyme, and perforin on TILs was also studied in both groups. TILs infiltrated along the margins of the ablated region in all HIFU-treated neoplasms, and the numbers of tumor-infiltrating CD3, CD4, CD8, CD4/CD8, B lymphocytes, and NK cells was increased significantly in the HIFU group. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly greater in the HIFU group than in the control group. HIFU ablation induced marked infiltration of CD3, CD4, CD8, B lymphocytes, and NK cells in the treated breast lesions. The number of FasL(+), granzyme(+), and perforin(+) TILs was significantly increased after HIFU treatment.

Radiofrequency ablation treatment for small breast cancer.

Abstract Abstract #5155 Aims: There is increasing demand for minimally invasive and non-surgical treatment in breast cancer. Although radiofrequency (RF) ablation seems the most promising non-surgical treatment for small breast cancer, its relevance has been controversial. This study was performed to determine the feasibility and the safety of treating small breast cancer with RF ablation. Methods: In this study, all patients had a localized breast cancer of 2.0 cm or less in greatest diameter. The tumors were confirmed to be localized lesions by ultrasonography, mammography, and enhanced MRI or CT. Before treatment, core needle or mammotome biopsy was performed to obtain the tumor tissue for establishing the histological diagnosis and the status of hormonal receptors and HER-2 expression. A model 15000 generator with a seven-array Starbusrt XL needle-electrode Model 70 (RITA Medical System) was used for RF ablation. In the first series, 17 patients underwent RF ablation and sentinel lymph node (SLN) biopsy followed immediately by wide resection (n=13) or total mastectomy (n=4). Axillary dissection was performed in 5 patients with positive SLN. On the other hand, 15 patients underwent RF ablation and SLN biopsy in the second series. Axillary dissection was performed in 3 patients with positive SLN. The ablated lesion was excised by mammotome after several months later. The ablated tumor tissue was examined histologically with H&E staining and NADH-diaphorase staining to assess tumor cell viability. Patients who underwent wide resection or RF ablation alone received breast irradiation, and all of the patients were treated with systemic therapy according to the St. Gallen recommendation. Results: Histological examination with H&E staining revealed a spectrum of changes ranging from complete coagulation necrosis to normal-appearing tumor cells, but NADH-diaphorase staining revealed no viable tumor cells in the either series. No patient developed to local or breast recurrence in the first series with a median follow-up period of 46 months (range: 34-61 months), and in the second series with a median follow-up period of 23 months (range: 12-32 months). However, one patient in the first series and another in the second series developed to the distant metastases, although they are alive with systemic treatment. The cosmesis of conserved breast was excellent in the second series more than in the first series, and no adverse effect such as skin burn or persistent hard lump was observed in the second series. Conclusions: RF ablation is feasible for small breast cancer. To achieve wide acceptance, however, further studies are needed to determine whether the use of RF ablation for small breast cancer can provide local control and survival rates equivalent to those of conventional breast-conserving treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5155.

Activation of Tumor-Infiltrating Antigen Presenting Cells by High Intensity Focused Ultrasound Ablation of Human Breast Cancer

Previous studies have shown that high intensity focused ultrasound (HIFU) ablation can trigger activation of host antitumor responses after direct tumor destruction. The goal of this study was to investigate the status and functions of tumor-infiltrating antigen presenting cells (APCs) after HIFU ablation of human breast cancer, and to explore the mechanisms regarding HIFU-enhanced antitumor response. Forty-eight women with biopsy-proven breast cancer were divided randomly into a control group ( n = 25) and a HIFU group ( n = 23). Patients in the control group received modified radical mastectomy, and those in the HIFU group underwent HIFU ablation of primary breast cancer, followed by modified radical mastectomy within 1–2 weeks. Using immunohistochemical analysis, tumor-infiltrating dendritic cells (DCs), macrophages, B lymphocytes and expression of HLA-DR and costimulatory molecules on DCs and macrophages were assessed in all patients. The results showed that APCs infiltrated along the margins of the ablated regions in all HIFU-treated tumors, and numbers of tumor-infiltrating DCs, macrophages and B lymphocytes increased significantly in the HIFU group. Compared with the values in the control group, the percentage of DCs and macrophages expressing HLA-DR, CD80 and CD86 was significantly greater in the HIFU group. There were statistically significant differences between numbers of S-100 + HLA-DR +, S-100 + CD80 +, S-100 + CD86 +, CD68 + HLA-DR +, CD68 + CD80 + and CD68 + CD86 + cells in the control and HIFU groups, respectively. It was concluded that HIFU ablation induces significant infiltration of APCs within the residual tumor debris in patients with breast cancer, and most of the tumor-infiltrating DCs and macrophages were activated after HIFU ablation. (E-mail: mfengwu@yahoo.com)

WITHDRAWN: Ovarian ablation for early breast cancer.

Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up. Trial identification procedures for the EBCTCG overviews have been described elsewhere. See under "EBCTCG" in the Breast Cancer Collaborative Review Group module. All properly randomised trials that began recruiting before 1990 which compared the ablation or suppression of ovarian function, sometimes with the addition of prednisone, versus no such adjuvant treatment for women with operable breast cancer. In practice, all the trials that can be reviewed here began before 1980, and all involved surgical or therapeutic ablation. In 1995, information was sought on each patient in any randomised trial of ovarian ablation or suppression versus control that began before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian ablation by irradiation or surgery, all of which began before 1980, but not for the four studies that assessed ovarian suppression by drugs, all of which began after 1985. Menopausal status was not consistently defined across trials; therefore, the main analyses are limited to women aged under 50 (rather than "premenopausal") when randomised. Oestrogen receptors were measured only in the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone. Among 2102 women aged under 50 when randomised, most of whom would have been premenopausal at diagnosis, 1130 deaths and an additional 153 recurrences were reported. 15-year survival was highly significantly improved among those allocated ovarian ablation (52.4 vs 46.1%, 6.3 [SD 2.3] fewer deaths per 100 women, logrank 2p=0.001), as was recurrence-free survival (45.0 vs 39.0%, 2p=0.0007). The numbers of events were too small for any subgroup analyses to be reliable. The benefit was, however, significant both for those with ("node positive") and for those without ("node negative") axillary spread when diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone, the benefit appeared smaller (even for women with oestrogen receptors detected on the primary tumour) than in the trials in the absence of chemotherapy (where the observed survival improvements were about six per 100 node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50 or over when randomised, most of whom would have been perimenopausal or postmenopausal, there was only a non-significant improvement in survival and recurrence-free survival. In women aged under 50 with early breast cancer, ablation of functioning ovaries significantly improves long-term survival, at least in the absence of chemotherapy. Further randomised evidence is needed on the additional effects of ovarian ablation in the presence of other adjuvant treatments, and to assess the relevance of hormone-receptor measurements.

Image-guided focused ultrasound ablation of breast cancer: current status, challenges, and future directions

Image-guided focussed ultrasound (FUS) ablation is a non-invasive procedure that has been used for treatment of benign or malignant breast tumours. Image-guidance during ablation is achieved either by using real-time ultrasound (US) or magnetic resonance imaging (MRI). The past decade phase I studies have proven MRI-guided and US-guided FUS ablation of breast cancer to be technically feasible and safe. We provide an overview of studies assessing the efficacy of FUS for breast tumour ablation as measured by percentages of complete tumour necrosis. Successful ablation ranged from 20% to 100%, depending on FUS system type, imaging technique, ablation protocol, and patient selection. Specific issues related to FUS ablation of breast cancer, such as increased treatment time for larger tumours, size of ablation margins, methods used for margin assessment and residual tumour detection after FUS ablation, and impact of FUS ablation on sentinel node procedure are presented. Finally, potential future applications of FUS for breast cancer treatment such as FUS-induced anti-tumour immune response, FUS-mediated gene transfer, and enhanced drug delivery are discussed. Currently, breast-conserving surgery remains the gold standard for breast cancer treatment.

Abstract No. 331: Percutaneous Radiofrequency Ablation for Primary Breast Cancer with Overlapping Technique

Abstract No. 331: Percutaneous Radiofrequency Ablation for Primary Breast Cancer with Overlapping Technique

MRI‐guided radiofrequency ablation of breast cancer: Preliminary clinical experience

This study was designed to demonstrate the feasibility of MRI-guided radiofrequency ablation (RFA) of breast cancer. A total of three women diagnosed with invasive ductal breast cancer were treated with percutaneous MRI-guided RFA, according to a treat and resect protocol, in our hospital. RFA procedures were performed in an open 0.5T Signa-SP imager allowing direct patient access and real-time monitoring of the procedure. In all patients ablation was performed with a 15-gauge insulated MRI-compatible multiple needle probe. MRI thermometry and contrast-enhanced postablation MRI were used to evaluate the ablation process. Patients underwent lumpectomy within a week of the RFA procedure. Histopathology confirmed successful (100%) tumor ablation in one patient, and partial tumor destruction (33% and 50%, respectively) in two patients. Challenges of MRI-guided breast RFA that need to be solved to facilitate progress of the technique toward clinical practice are discussed.

2066 POSTER Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: first results of a feasibility study

2066 POSTER Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: first results of a feasibility study

Re: Ovarian Ablation or Suppression in Premenopausal Early Breast Cancer: Results from the International Adjuvant Breast Cancer Ovarian Ablation or Suppression Randomized Trial

Re: Ovarian Ablation or Suppression in Premenopausal Early Breast Cancer: Results from the International Adjuvant Breast Cancer Ovarian Ablation or Suppression Randomized Trial

PI3K activation is associated with intracellular sodium/iodide symporter protein expression in breast cancer

BackgroundThe sodium/iodide symporter (NIS) is a membrane glycoprotein mediating active iodide uptake in the thyroid gland and is the molecular basis for radioiodide imaging and therapeutic ablation of thyroid carcinomas. NIS is expressed in the lactating mammary gland and in many human breast tumors, raising interest in similar use for diagnosis and treatment. However, few human breast tumors have clinically evident iodide uptake ability. We previously identified PI3K signaling as important in NIS upregulation in transgenic mouse models of breast cancer, and the PI3K pathway is commonly activated in human breast cancer.MethodsNIS expression, subcellular localization, and function were analyzed in MCF-7 human breast cancer cells and MCF-7 cells stably or transiently expressing PI3K p110alpha subunit using Western blot of whole cell lysate, cell surface biotinylation Western blot and immunofluorescence, and radioiodide uptake assay, respectively. NIS localization was determined in a human breast cancer tissue microarray using immunohistochemical staining (IHC) and was correlated with pre-existing pAkt IHC data. Statistical analysis consisted of Student's t-test (in vitro studies) or Fisher's Exact Test (in vivo correlational studies).ResultsIn this study, we demonstrate that PI3K activation in MCF-7 human mammary carcinoma cells leads to expression of underglycosylated NIS lacking cell surface trafficking necessary for iodide uptake ability. PI3K activation also appears to interfere with cell surface trafficking of exogenous NIS as well as all-trans retinoic acid-induced endogenous NIS. A correlation between NIS expression and upregulation of PI3K signaling was found in a human breast cancer tissue microarray.ConclusionThus, the PI3K pathway likely plays a major role in the discordance between NIS expression and iodide uptake in breast cancer patients. Further study is warranted to realize the application of NIS-mediated radioiodide ablation in breast cancer.

High-intensity focused ultrasound ablation of breast cancer

The noninvasive ablation of tumors with high-intensity focused ultrasound (HIFU) energy has received increasingly widespread interest. The temperature within the focal volume of an ultrasound beam is rapidly raised to cytotoxic levels. HIFU can selectively ablate a targeted tumor at depth without any damage to surrounding or overlying tissues. Animal studies have shown that HIFU ablation is safe and effective for the treatment of implanted breast malignancies. The results from early clinical trials (Phase I and II) are encouraging, suggesting that HIFU is a promising treatment for small breast cancer. Once oncologic efficacy data from large-scale randomized clinical trials are available, HIFU ablation may become an attractive treatment option for patients with small breast cancer, especially the elderly.

Ovarian Ablation or Suppression in Premenopausal Early Breast Cancer: Results From the International Adjuvant Breast Cancer Ovarian Ablation or Suppression Randomized Trial

Substantial survival benefits exist for patients with early-stage breast cancer who undergo treatment with single-modality tamoxifen, ovarian ablation or suppression, or chemotherapy. To determine whether additional benefits exist with combined treatment, the Adjuvant Breast Cancer (ABC) Trials were undertaken. The ABC Ovarian Ablation or Suppression Trial randomly assigned pre- and perimenopausal patients with early-stage breast cancer who were receiving prolonged (5 years) tamoxifen treatment with or without chemotherapy to ovarian ablation or suppression (by oophorectomy, ovarian irradiation, or treatment with luteinizing hormone-releasing hormone agonist) versus no ovarian ablation or suppression. Trial endpoints included relapse-free and overall survival. Hazard ratios (HRs) were derived from Cox models, and all statistical tests were two-sided. Between 1993 and 2000, 2144 (1063 ovarian ablation or suppression, 1081 no ovarian ablation or suppression) patients were randomly assigned. A total of 942 (89%) received ovarian ablation or suppression as allocated. Overall, no evidence of a benefit for ovarian ablation or suppression was observed for relapse-free survival (relapse in the ovarian ablation/suppression versus no ovarian ablation/suppression group, 290 events versus 306 events, HR = 0.95, 95% confidence interval [CI] = 0.81 to 1.12; P = .56) or overall survival (death from any cause in the ovarian ablation or suppression versus no ovarian ablation/suppression group, 215 events versus 230 events, HR = 0.94, 95% CI = 0.78 to 1.13; P = .44), nor were differences seen after adjustment for age, nodal status, or estrogen receptor (ER) status. Overall, no added effect of ovarian ablation or suppression was seen on relapse-free survival or overall survival of premenopausal women who were treated for early-stage breast cancer. However, the role of ovarian ablation or suppression in young (<40 years) women with ER-positive tumors, especially those not receiving chemotherapy, requires further study.

Focused Ultrasound Hones Breast Cancer Ablation

Focused Ultrasound Hones Breast Cancer Ablation

The evolving non-surgical ablation of breast cancer: Mr Guided focused ultrasound (MRgFUS)

MRgFUS (MR guided Focused Ultrasound) being one of the non-surgical ablation techniques. We have already achieved favorable results in the past clinical study of MRgFUS to local treatment. New twenty one cases of invasive/noninvasive ductal carcinoma of the breast were treated by MRgFUS. Core needle biopsy led to the definitive diagnosis. All the patients were positioned prone in the treatment, using the therapeutic apparatus such as Signa Excite 1.5 T for MRI and ExAblate 2000 version 2.6/4.1 for FUS. Irradiation was not applied to all the 21 cases after MRgFUS. Axillary lymph node metastases were examined by dissection or sentinel lymph node biopsy. Recurrence or abnormal area of residual cancer was treated with Re-MRgFUS or ablated by usual surgery. All the 21 cases were from women patients. Median age is 54 years (range: 34-72). Median diameter of tumor is 15 mm (range: 5-50). As for the numbers of treatment, 17 patients were treated once, and 4 patients twice. Median period of observation is 14 months (range: 3-26). One case of recurrence of pure mucinous carcinoma was experienced. No evidences of recurrence were obtained through MRI for the rest of 20 cases. Skin burns were found in 2 cases. The patient had dimple on the skin immediately above tumor. In conclusion, MRgFUS is a good mean as local control of breast cancer, but the indicated case must be selected strictly. And it needs to observe longer the patients who ware treated by MRgFUS alone.

284 POSTER Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: first results of a feasibility study

284 POSTER Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: first results of a feasibility study

Diagnosis of aspergilloma in a pleural cavity (persistent pneumothorax) using classic imaging methods

The diagnosis of pulmonary aspergillosis is based on serum-analysis, as well as histological and microbiological analysis of bronchial lavage and transbronchial biopsies. When Aspergillus develops within a preformed cavity, however, these tests are likely to be negative. In this situation, classic imaging techniques such as chest X-ray and high resolution-computed tomography (HR-CT) can be of great diagnostic use. We here describe the case of a 62-year-old woman with a history of breast cancer and subsequent ablation of the left breast and radiotherapy. The case demonstrates an example of a pleuropulmonary aspergilloma, in which sero- and micro-biological detection failed. Thorax HR-CT exhibited the cavity, a small persistent pneumothorax, partially filled by an oval density. This density clearly dislocated according to gravity following a positional change of the patient from supine to prone. The density thus revealed mobility which was typical of aspergilloma. Following excision, this diagnosis was confirmed. A density within a cavity may be differentiated by its mobility from differential diagnoses such as lung cancer which would not be expected to exhibit mobility.

Breast Cancer Ablation: Current Status 2006

The decrease in average size of breast cancer at presentation has spurred interest into less invasive forms of local treatment. Techniques to ablate breast cancer within the breast without surgery are being studied in many countries. Interdisciplinary comprehensive breast centers strive to keep current with new technologies such as ablation. The goal of these efforts is to destroy the breast cancer effectively with minimally invasive methods and in a patient-friendly manner. Current methods of breast cancer ablation are reviewed and compared in effectiveness, ease of use, cost, discomfort, and existing published data. A major hurdle for all methods is to identify proper candidates for targeted ablation. When pretreatment imaging identifies truly unifocal breast cancers, one or more of these methods will be ready to treat these small unifocal cancers effectively.

Radiofrequency ablation of small breast cancer followed by surgical resection

With the growing demand from patients for less-invasive procedures, the shift from surgical extirpation to ablative local control of breast tumors is an emerging focus in breast cancer care. This study was performed to determine the feasibility and safety of treating small breast cancer with radiofrequency (RF) ablation. Patients with biopsy-proven invasive or non-invasive breast cancer underwent RF ablation under general anesthesia. Before RF ablation, all patients were confirmed to have a localized lesion using imaging modalities. Wide excision or total mastectomy with sentinel lymph node biopsy or axillary lymph node dissection was performed. The resected tumor was examined histologically with hematoxylin-eosin (H&E) and nicotinamide adenine dinucleotide-diaphorase (NADH) staining. Ten patients completed the treatment without RF ablation-related complications. The mean tumor size was 1.1 cm (range: 0.5-2.0 cm). Histological evaluation of the ablated tissue using H&E staining revealed a spectrum of changes ranging from complete coagulation necrosis of tumor cells to normal-appearing tumor cells. However, NADH-diaphorase showed no staining of viable tumor cells in the RF-ablated region in all of the patients. RF ablation is promising as a minimally invasive ablation technique in the local treatment of invasive or non-invasive breast cancer. However, further study is necessary before RF ablation can replace conventional breast conservation therapy for patients with small breast cancer.

Influence of electrical and thermal properties on RF ablation of breast cancer: is the tumour preferentially heated?

BackgroundTechniques based on radio frequency (RF) energy have many applications in medicine, in particular tumour ablation. Today, mammography screening detects many breast cancers at an early stage, facilitating treatment by minimally invasive techniques such as radio frequency ablation (RFA). The breast cancer is mostly surrounded by fat, which during RFA-treatment could result in preferential heating of the tumour due to the substantial differences in electrical parameters. The object of this study was to investigate if this preferential heating existed during experimental in vitro protocols and during computer simulations.MethodsExcised breast material from four patients with morphologically diagnosed breast cancers were treated with our newly developed RFA equipment. Subsequently, two finite element method (FEM) models were developed; one with only fat and one with fat and an incorporated breast cancer of varying size. The FEM models were solved using temperature dependent electrical conductivity versus constant conductivity, and transient versus steady-state analyses.ResultsOur experimental study performed on excised breast tissue showed a preferential heating of the tumour, even if associated with long tumour strands. The fat between these tumour strands was surprisingly unaffected. Furthermore, the computer simulations demonstrated that the difference in electrical and thermal parameters between fat and tumour tissue can cause preferential heating of the tumour. The specific absorption rate (SAR) distribution changed significantly when a tumour was present in fatty tissue. The degree of preferential heating depended on tissue properties, tumour shape, and placement relative to the electrode. Temperature dependent electrical conductivity increased the thermal lesion volume, but did not change the preferential heating. Transient solutions decreased the thermal lesion volume but increased the preferential heating of the tumour.ConclusionBoth the computer model and the in vitro study confirmed that preferential heating of the tumour during RFA exists in breast tissue. However, the observed preferential heating in the in vitro studies were more pronounced, indicating that additional effects other than the difference in tissue parameters might be involved. The existing septa layers between the cancer tissue and the fatty tissue could have an additional electrical or thermal insulating effect, explaining the discrepancy between the in vitro study and the computer model.

High-Intensity Focused Ultrasound Ablation: Will Image-guided Therapy Replace Conventional Surgery?

HomeRadiologyVol. 235, No. 2 Next Science to PracticeHigh-Intensity Focused Ultrasound Ablation: Will Image-guided Therapy Replace Conventional Surgery?Ethan J. HalpernEthan J. HalpernAuthor Affiliations1Department of Radiology, Thomas Jefferson University Hospital, Jefferson Prostate Diagnostic Center, 132 S 10th St, Philadelphia, PA 19107-5244 [email protected]Ethan J. HalpernPublished Online:May 1 2005https://doi.org/10.1148/radiol.2352041774MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References 1 Wu F, Wang ZB, Chen WZ, et al. Advanced hepatocellular carcinoma: treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization. Radiology 2005; 235:659-667. Link, Google Scholar2 Kennedy JE, Ter Harr GR, Cranston D. High intensity focused ultrasound: surgery of the future? Br J Radiol 2003; 76:590-599. Crossref, Medline, Google Scholar3 Thuroff S, Chaussy C, Vallancien G, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol 2003; 17:673-677. Crossref, Medline, Google Scholar4 Tempany CM, Stewart EA, McDannold N, Quade BJ, Jolesz FA, Hynynen K. MR imaging–guided focused ultrasound surgery of uterine leiomyomas: a feasibility study. Radiology 2003; 226:897-905. Link, Google Scholar5 Hynynen K, Jolesz FA. Demonstration of potential noninvasive ultrasound brain therapy through intact skull. Ultrasound Med Biol 1998; 24:275-283. 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