Wolfram Malter

Impact of clinical and lesion characteristics on the results of MR-guided wire localizations of the breast using an open 1.0-T MRI system.

PurposePreoperative magnetic resonance (MR)–guided wire localizations are warranted in patients with suspicious focal breast lesions on MR mammographic findings without equivalent in x-ray mammography and ultrasonography. The study was performed to assess the impact of clinical parameters, tumor size, and target localization on the procedural characteristics in magnetic resonance imaging (MRI)–guided wire localizations of breast lesions using an open 1.0-T open MR system. Material and MethodsThe clinical, radiological, and histological characteristics of all 347 patients and all 394 interventional procedures performed in a 6-year interval were extracted from the clinical files. Two board-certified senior radiologists evaluated the impact of target localization and the size on the interventional results in the available 302 image data sets. Patient characteristics, lesion characteristics, and interventional results were statistically correlated in subgroup analyses. ResultsA total of 387 of the 394 MR-guided wire localizations (98.2%) were technically successful. In 7 cases (2.3%), the intervention was aborted because the suspicious finding of the diagnostic MR mammography could not be visualized during the intervention. Minor complications occurred in 13 interventions (3.3%). The histological workup of the operative specimen showed benign results in 226 of the 394 interventions (57.4%) and malignant findings in 154 wire localizations (39.1%). The mean (SD) length of the interventional procedure time defined as the time interval between the start of the first and of the last MRI sequence as documented in the electronic MRI data sets was 24.6 (8.4) minutes. Patient age, medical history, and the anticipated risk for developing breast cancer and a simultaneous known carcinoma did not affect the technical success and complication rates and the interventional procedure time. A total of 60 targets (19.5%) were located in the retromamillary zone, 89 targets (28.9%) in the peripheral zone, and 1 target (0.3%) near the chest wall. The maximum diameter was 1 to 5 mm in 64 lesions (21.2%), 6 to 10 mm in 136 lesions (45.0%), 11 to 15 mm in 56 lesions (18.6%), and 16 mm or greater in 46 lesions (15.2%). A total of 23 of the 100 histologically proven invasive carcinomas had a maximum MRI diameter of 1 to 5 mm (23.0%) and 38 (38.0%) of 6 to 10 mm. ConclusionsMagnetic resonance–guided wire localizations of suspicious breast lesions using an open high-field MR system are a clinically safe and feasible method even in small target lesions and anatomical regions that are usually considered difficult to access.

Intraoperative Boost Radiotherapy during Targeted Oncoplastic Breast Surgery: Overview and Single Center Experiences

Breast-conserving surgery followed by whole-breast irradiation is the standard local therapy for early breast cancer. The international discussion of reduced importance of wider tumor-free resection margins than “tumor not touching ink” leads to the development of five principles in targeted oncoplastic breast surgery. IORT improves local recurrence risk and diminishes toxicity since there is less irradiation of healthy tissue. Intraoperative radiotherapy (IORT) can be delivered in two settings: an IORT boost followed by a conventional regimen of external beam radiotherapy or a single IORT dose. The data from TARGIT-A and ELIOT reinforce the conviction that intraoperative radiotherapy during breast-conserving surgery is a reliable alternative to conventional postoperative fractionated irradiation, but only in a carefully selected population at low risk of local recurrence. We describe our experiences with IORT boost (50 kV energy X-rays; 20 Gy) in combination with targeted oncoplastic breast surgery in a routine clinical setting. Our experiences demonstrate the applicability and reliability of combining IORT boost with targeted oncoplastic breast surgery in breast-conserving therapy of early breast cancer.

Oncoplastic breast reconstruction after IORT

Prospective randomized clinical trials have shown that breast-conserving surgery followed by radiotherapy gives equivalent survival rates compared with mastectomy. The indications for breastconserving therapy in breast cancer are expanding. The integration of oncoplastic surgery techniques with breast-conserving segmentectomy is a new approach that allows more extensive resections and results in more cosmetic favourable outcomes. During the last years we have defined five reconstruction principles in oncoplastic breast-conserving surgery. With these five principles we were able to perform more than 95% of all immediate reconstructions of partial mastectomy defects during breast-conserving surgery, resulting in optimized local and aesthetic outcomes. The oncoplastic reconstruction principles of partial mastectomy defects during breast-conserving surgery are as follows: glandular rotation, dermoglandular rotation, tumoradapted reduction mammoplasty, thoracoepigastric flap, Latissimus dorsi flap. Usually the whole breast is percutaneously irradiated after breast-conserving surgery. Depending on different risk factors, a local boost dose is applied to the tumor bed, which leads to a further reduction of local recurrences. Recently, the concept of intraoperative radiotherapy (IORT) as boost during breast-conserving surgery has been introduced internationally. From a surgical point of view intraoperative boost radiotherapy with a mobile device generating low-energy X-rays (Intrabeam ® ) can be combined with all oncoplastic principles for reconstructing partial mastectomy defects. The advantage of an oncoplastic reconstruction after breastconserving surgery and IORT boost irradiation should be recommended to improve local outcome, to avoid seroma formation and to improve the cosmetic outcome after treatment.

Tamoxifen Treatment in Correlation with Increased ET-1 Levels Is Associated with the Development of Breast Cancer Metastases

Background: In breast cancer patients, a correlation between endothelin-1 (ET-1) and lymph node metastasis was found. While breast cancer with a positive ER status can be treated with Tamoxifen, several studies describe increasing Tamoxifen resistance in patients. We analyzed the relationship between Tamoxifen, ET-1 overexpression, and ER leading to Tamoxifen resistance. Methods: Breast cancer cell lines were treated with Tamoxifen, ET-1, estrogen and combinations. Using qRT-PCR, immune-precipitation, Western blot, EMSA and immunohistology target gene expression and ER complex partners were investigated. Human biopsies and mastectomy specimens were immunohistologically studied for Vimentin 3, and ERβ. Results: Breast cancer cells stimulated with a combination of Tamoxifen and ET-1 downregulate ERα, while upregulating intracellular ET-1, and ERβ. Immunoprecipation of nuclear extracts with ET-1, ERα or ERβ agarose conjugated antibodies reveals a complex formation change replacing ERα by ERβ once Tamoxifen forms a complex with ET-1. ERβand ET-1 migrate into the nucleus. ET-1 stimulation upregulates metastases promoting target genes (IL-6, Wnt11), including a novel one, Vimentin 3. Tissue analyses show Vim3 and ERβ expression in metastases of ERα positive breast cancer, and in ERα negative biopsies/mastectomy specimens. Conclusion: We are the first to describe a complex consisting of Tamoxifen, ERβ and ET-1, whose nuclear transmigration causes an overexpression of target genes. This mechanism may explain Tamoxifen resistance. Future pathologic analyses should include estrogen beta receptor status as well as the ET-1 expression. This concept presents a new treatment approach for individualized medicine in breast cancer patients with increased ET-1 levels.

Profile and Outcome of Supraclavicular Metastases in Patients with Metastatic Breast Cancer: Discordance of Receptor Status Between Primary and Metastatic Site

Background: Breast cancer is a heterogenous and complex disease. A rare site of metastatic breast cancer disease is the neck. Data about supraclavicular metastases in patients with metastatic breast cancer are still lacking. Hence, our study aimed to analyze histological subtypes of supraclavicular metastases compared to the primary site. Materials and Methods: This was a retrospective hospital-based cohort study of patients with breast cancer who developed supraclavicular metastases. Diagnosis of supraclavicular metastases was confirmed by biopsy or diagnostic lymph node extirpation. Histological subtypes were analyzed and Kaplan–Meier estimates were calculated for overall survival. Results: A total of 20 patients were included in the analysis. The majority of the patients (12/20) had hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative supraclavicular metastases, disease in 3/20 patients was HR-positive/HER2-positive, HR-negative/HER2-positive in 1/20 patients and basal-like in 4/20 patients. Total discordance rates for estrogen receptor, progesterone receptor and HER2 between primary and metastatic tumors were 20.0%, 36.8% and 29.4%, respectively. The 5-year overall survival was 80%, whereas the 5-year survival after the onset of neck metastasis was 45%. Conclusion: As a rare site of metastatic breast cancer, supraclavicular metastases are associated with a worse median overall survival from their onset. The high rate of discordance of histological subtype stresses the necessity for biopsies in patients with supraclavicular metastasis.

Factors Predictive of Sentinel Lymph Node Involvement in Primary Breast Cancer

Background/Aim: Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) for axillary staging in patients with early-stage breast cancer. The need for therapeutic ALND is the subject of ongoing debate especially after the publication of the ACOSOG Z0011 trial. In a retrospective trial with univariate and multivariate analyses, factors predictive of sentinel lymph node involvement should be analyzed in order to define tumor characteristics of breast cancer patients, where SLNB should not be spared to receive important indicators for adjuvant treatment decisions (e.g. thoracic wall irradiation after mastectomy with or without reconstruction). Patients and Methods: Between 2006 and 2010, 1,360 patients with primary breast cancer underwent SLNB with/without ALND with evaluation of tumor localization, multicentricity and multifocality, histological subtype, tumor size, grading, lymphovascular invasion (LVI), and estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status. These characteristics were retrospectively analyzed in univariate and multivariate logistic regression models to define significant predictive factors for sentinel lymph node involvement. The multivariate analysis demonstrated that tumor size and LVI (p<0.001) were independent predictive factors for metastatic sentinel lymph node involvement in patients with early-stage breast cancer. Conclusion: Because of the increased risk for metastatic involvement of axillary sentinel nodes in cases with larger breast cancer or diagnosis of LVI, patients with these breast cancer characteristics should not be spared from SLNB in a clinically node-negative situation in order to avoid false-negative results with a high potential for wrong indication of primary breast reconstruction or wrong non-indication of necessary post-mastectomy radiation therapy. The prognostic impact of avoidance of axillary staging with SLNB is analyzed in the ongoing prospective INSEMA trial.

Lung Metastasectomy for Pulmonary Metastatic Breast Carcinoma

Breast carcinoma with pulmonary metastasis can be treated locally or systemically. Following primary tumour resection patients with isolated, completely resectable pulmonary nodules and definite functional operability can be offered lung metastasis resection. Following metastasectomy a median survival of 32 to 96.6 months can be achieved with corresponding five-year survival rates between 30.8 and 54.4%. The procedure is associated with a mortality rate of 0 to 3%. The most important independent prognostic factor for long-term survival is complete resection of all lung lesions. The configuration and pattern of metastasis as well as disease-free interval, hormone and HER2/neu receptor status also appear to influence prognosis, but are of lesser importance. Intrapulmonary recurrence of metastases may, after careful selection on a case-by-case basis, also be treated operatively. In some cases this is associated with a favourable long-term prognosis. Pulmonary metastasectomy should be the treatment of choice for selected patients with metastatic breast carcinoma.

MRT-gesteuerte Vakuumbiopsien (VAB) der Mamma an einem 1.0 T Tomographen: Einfluss klinischer, sowie Läsionscharakteristika auf den Interventionsprozess und das klinische Outcome

Die kontrastmittelgestutzte MR-Tomografie der Mamma bietet die Moglichkeit klinisch okkulte sowie Rontgen-mammographisch und sonographisch nicht zu detektierende Befunde nachzuweisen. Bei fehlender Reproduzierbarkeit einer MR-tomographisch nachgewiesenen Lasion der MRT-BI-RADS Kategorie 4 oder 5 ohne Korrelat in der Rontgen-Mammografie und der Sonografie ist die Indikation zu einer MRT-gestutzten perkutanen Intervention gegeben. Die Studie hatte das Ziel den Einfluss klinischer, sowie Lasionscharakteristika auf den Interventionsprozess sowie das klinische Outcome an einem 1.0 T Tomographen zu beurteilen. Klinische, bildmorphologische sowie histopathologische Befunde aller 132 Patientinnen, welche eine Erstintervention per VAB zwischen 07/2005 und 03/2012 im Institut fur Diagnostische und Interventionelle Radiologie der Universitatsklinik Koln erhielten und wurden aus den handischen und elektronischen Krankenakten extrahiert. Die Daten wurden anhand eines strukturierten, elektronischen Fragebogens erfasst und in Form einer elektronischen Datenbank angelegt. Der weitere klinische Verlauf aller Patientinnen mit benignen Befunden wurde anhand der Datenerfassung durch die behandelnden, niedergelassenen Gynakologen beurteilt. Sowohl Lage als auch Grose der untersuchten Ziellasionen aller 103 verfugbarer Datensatze wurden im Sinne einer Doppelbefundung von 2 radiologischen Oberarzten befundet. Einfluss der Lokalisation und der Bildmorphologie auf die technischen und klinischen Kenndaten, insbesondere der Lage der Ziellasion, Grose und der Sichtbarkeit der Ziellasion vor und nach Kontrastmittelgabe auf das interventionelle und klinische Outcome wurden in Subgruppenanalysen uberpruft. 131 von 132 MR-gesteuerten Brustbiopsien (99,2%) waren technisch erfolgreich. Die mediane Interventionszeit betrug 30 Minuten (25% Perzentile 25 Minuten, 75% Perzentile 35 Minuten, max. 75 Minuten.) Minor Komplikationen traten in 13 Fallen auf (3, 3%). Die histopathologische Befundung zeigte benigne Befunde in 95 der 132 Interventionen (72%), B3-Lasionen, also Lasionen mit unklarem biologischem Potential fanden sich in 6 Biopsien (4,5%) und maligne Befunde in insgesamt 30 Biopsien (23,5%). Weder das Alter der Patientinnen, noch die bisherige klinisch-onkologische Anamnese hatten Einfluss auf den technischen Erfolg, die Komplikationsraten oder die Interventionszeit. Die maximale Lasionsgrose lag zwischen 1 und 5 mm in 16 Fallen (15,5%), 6 bis 10 mm in 41 Fallen (39,8%) und 11 bis 15 mm in 29 Fallen (28,2%) in den 108 vorhandenen retrospektiv ausgewerteten Daten. Insgesamt ergaben sich 2 falsch negative histopathologische Befunde (2,4%) der 70 Patienten mit benignen Befunden. MRT-gesteuerte Vakuumbiopsien suspekter Lasionen der Brust an einem offenen 1.0 T Tomographen sind eine klinisch sichere und praktikable Methode besonders fur kleine und anatomisch diffizil gelegene Befunde.