Matthias W. Beckmann

Gene Amplification and Overexpression of CDK4 in Sporadic Breast Carcinomas Is Associated with High Tumor Cell Proliferation

Amplification of the cyclin-dependent kinase 4 (CDK4) gene, located at 12q13-q14, has been found as an alternative genetic alteration to CDKN2A inactivation in various human tumors including malignant gliomas and sarcomas. In the present study, we have evaluated the frequency of the CDK4 gene amplification in sporadic breast cancer by applying a nonradioactive quantitative differential polymerase chain reaction based on fluorescent DNA technology. Fluorescent-labeled polymerase chain reaction products were analyzed with an automated DNA sequencer. Amplification of CDK4 gene was detected in 15 (15.8%) of 95 breast cancers. All tumors with CDK4 gene amplification showed high CDK4 protein expression determined by immunohistochemistry. Furthermore, the mean Ki-67 labeling index in tumors with CDK4 gene amplification was significantly higher than in those without CDK4 gene amplification. No significant associations were observed between CDK4 gene amplification and any specific histopathological parameter. The findings of this study provide the first evidence of CDK4 gene amplification in breast cancer and suggest that CDK4 gene amplification appears to be of importance in the pathogenesis of a subset of sporadic breast cancer.

Evaluation of a Marker Clip System in Sonographically Guided Core Needle Biopsy for Breast Cancer Localization Before and After Neoadjuvant Chemotherapy

Introduction The placement of intramammary marker clips has proven to be helpful for tumor localization in patients undergoing neoadjuvant chemotherapy and breast-conserving surgery. The purpose of our study was to investigate the feasibility of using a clip marker system for breast cancer localization and its influence on the imaging assessment of treatment responses after neoadjuvant chemotherapy. Patients and Methods Between March and June 2015, a total of 25 patients (n = 25), with a suspicion of invasive breast cancer with diameters of at least 2 cm (cT2), underwent preoperative sonographically guided core needle biopsy using a single-use breast biopsy system (HistoCore™) and intramammary clip marking using a directly adapted clip system based on the established O-Twist Marker™, before their scheduled preoperative neoadjuvant chemotherapy. Localization of the intramammary marker clip was controlled by sonography and digital breast tomosynthesis. Results Sonography detected no dislocation of intrammammary marker clips in 20 of 25 patients (80 %), while digital breast tomosynthesis showed accurate placement without dislocation in 24 patients (96 %) (p < 0.05). There was no evidence of significant clip migration during preoperative follow-up imaging after neoadjuvant chemotherapy. No complication related to the clip marking was noted and there was no difficulty in evaluating the treatment response to neoadjuvant chemotherapy. Among the breast-conserving surgeries performed, no cases were identified in which intraoperative loss of the marker clip had occurred. Conclusion Our study underscores the importance of intramammary marking clip systems before neoadjuvant chemotherapy. Placement of marker clips is advised to facilitate accurate tumor bed localization. With regard to digital breast tomosynthesis, its development continues to improve the quality of diagnostics and the therapy of breast cancer particularly for small breast cancer tumors or in neoadjuvant chemotherapy setting.

Fully Automated Nipple Detection in 3D Breast Ultrasound Images

Nipple position provides useful diagnostic informations in reading automated 3D breast ultrasound (ABUS) images. The identification of nipples is required to localize and determine the quadrants of breast lesions. Additionally, the nipple position serves as an effective landmark to register an ABUS image to other imaging modalities, such as digital mammography, breast magnet resonance imaging (MRI), or tomosynthesis. Nevertheless, the presence of speckle noise induced by interference waves and variant imaging directions in ultrasonography poses challenges to the task. In this work, we propose a fast and automated algorithm to detect nipples in 3D breast ultrasound images. The method fully takes advantages of the consistent characteristics of ultrasonographic signals observed at nipples and employs a multi-scale Laplacian-based blob detector to eventually identify nipple positions. The accuracy of the proposed method was tested on 113 ABUS images, resulting in a distance error of 6.6±8.9 mm (mean ±std).

Risikoadaptierte Diagnostik und Therapie

Das Mammakarzinom ist die haufigste Malignomerkrankung bei Frauen. Fur eine erfolgreiche Diagnostik und Pravention des Mammakarzinoms ist daher eine moglichst genaue Bestimmung des individuellen Erkrankungsrisikos essenziell. In den letzten Jahren wurden neue Erkenntnisse bezuglich einerseits genetischer Risikofaktoren und andererseits auch deren Interaktion mit etablierten klinischen Risikofaktoren gewonnen. Diese Informationen beeinflussen das klinische Management von Brustkrebs zentral und sind Teil des Weges zu einer personalisierten Diagnostik und Therapie.

Nachsorge mit Rezidiv- und Metastasensuche und Therapiebegleitung

Das Mammakarzinom ist die haufigste Krebserkrankung der Frau und insgesamt fur mehr als 27% aller Krebserkrankungsfalle bei Frauen verantwortlich. Insgesamt wird also jede achte Frau im Laufe ihres Lebens diesem schicksalhaften Einschnitt gegenuber stehen, welcher sowohl sie als Individuum als auch ihre Umgebung betrifft.