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Grating-based X-ray dark-field imaging is a new imaging modality. It allows the visualization of structures at micrometer scale due to small-angle scattering of the X-ray beam. However, reading dark-field images is challenging as absorption and edge-diffraction effects also contribute to the dark-field signal, without adding diagnostic value. In this paper, we present a novel – and to our knowledge the first – algorithm for isolating small-angle scattering in dark-field images, which greatly improves their interpretability. To this end, our algorithm utilizes the information available from the absorption and differential phase images to identify clinically irrelevant contributions to the dark-field image. Experimental results on phantom and ex-vivo breast data promise a greatly enhanced diagnostic value of dark-field 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).

Preoperative staging of breast cancer based on breast imaging is mandatory. Breast imaging is a general term that encompasses mammography, breast sonography, and magnetic resonance tomography (MRT) of the breast (magnetic resonance mammography, MRM). It is known that earlier diagnosis of breast cancer is more likely to result in a favorable oncological outcome. In this context, use and limitations of MRM in diagnosis and staging of breast cancer as well as its influence on surgical procedures have to be discussed. Different interventional procedures have been developed. The histological results of interventional procedures guided by ultrasound, stereotactic mammography or MRT have to be integrated in planning surgical resection margins in oncoplastic breast-conserving surgery. Image-guided wire markings are an important tool for planning these surgical resection margins. This paper gives an overview on the importance of breast imaging, interventional procedures, and wire markings for breast-conserving surgical therapy. Die komplementäre Mammadiagnostik bildet die Grundlage für das präoperative Staging beim Mammakarzinom. Zur komplementären Mammadiagnostik gehören im Speziellen die Mammografie, die Mammasonografie und die Magnetresonanztomografie (MRT) der Mamma (Magnetresonanz-Mammografie, MRM). Je früher die Diagnose eines Mammakarzinoms erfolgt, desto besser ist die Prognose. In diesem Zusammenhang müssen besonders Stellenwert, Einsatz und Limitationen der MRM bei Diagnose und Staging des Mammakarzinoms sowie ihre Auswirkungen auf das operative Vorgehen diskutiert werden. Die histologischen Ergebnisse nach sonografisch, stereotaktisch oder MRT-gesteuerter interventioneller Diagnostik sollten in die Planung der Resektionsgrenzen im Rahmen der brusterhaltenden, onkoplastischen Mammachirurgie integriert werden. Für die Planung der Resektionsgrenzen stellen die unterschiedlichsten bildgebend gesteuerten Markierungstechniken wichtige Instrumente dar. Diese Arbeit gibt einen aktuellen Überblick über die Bedeutung der bildgebenden Mammadiagnostik, der interventionellen Diagnostik und der Markierungstechniken für die Planung und Durchführung der brusterhaltenden, operativen Therapie des Mammakarzinoms.

An increasing number of breast cancer patients are undergoing pre-operative (neoadjuvant) chemotherapy regimens. Primary systematic chemotherapy frequently reduces the tumour volume, which increases the frequency of successful breast-conserving therapy [1]. The accurate pre-operative assessment and monitoring has become an important component to comprehensive therapy for patients with breast cancer. Currently, in clinical practice, Clinical Breast Examination (CBE), Ultrasound, Digital Mammography (DM), MRI, Elastography are evaluating the therapeutic effect of chemotherapy.

Mastectomy specimens were investigated using a Talbot-Lau X-ray imaging set-up. Significant structures in the darkfield were observed, which revealed considerably higher contrast than those observed in digital mammography. Comparison with the histomorphometric image proofs that the darkfield signal correlates with a tumor region containing small calcification grains of 3 to 30 μm size.

There is growing evidence that certain breast cancer (BC) risk factors specifically increase the risk for specific molecular tumor subtypes. Different molecular subtypes of BC can partly be described by analyzing proliferation in tumors. Very few data are available regarding the association of mammographic density (MD), as a BC risk factor, with proliferation. The aim of this study was to analyze the association between Ki-67 expression in BCs and MD. In this case-only study, data on BC risk factors, hormone receptor expression, and MD were available for 1,975 patients with incident BC. MD was assessed as percentage mammographic density (PMD) using a semiautomated method by two readers for every patient. The association of the Ki-67 proliferation index and PMD was studied using multifactorial analyses of covariance (ANCOVA), with PMD as the target variable and including well-known factors that are also associated with MD such as age, parity, use of hormone replacement therapy (HRT), and body mass index (BMI). There were no significant differences in PMD between women with BC who had low and high Ki-67 values (P = 0.31). However, there were relevant differences in women with low BMI (P = 0.07), and in women using postmenopausal HRT (P = 0.06) as well as in women with low PR values (P = 0.07). In these subgroups, the Ki-67 expression index increased with decreasing PMD. Likewise PMD is correlated with BMI, parity status, and menopausal status stronger in patients with low proliferating tumors, and with progesterone receptor expression in patients with high proliferating tumors. MD correlates inversely with Ki-67 proliferation in BC tumors only in some subgroups of BC patients, defined by commonly known BC risk factors that are usually associated with MD as well.

For many breast cancer (BC) risk factors, there is growing evidence concerning molecular subtypes for which the risk factor is specific. With regard to mammographic density (MD), there are inconsistent data concerning its association with estrogen receptor (ER) and progesterone receptor (PR) expression. The aim of our study was to analyze the association between ER and PR expression and MD. In our case-only study, data on BC risk factors, hormone receptor expression and MD were available for 2,410 patients with incident BC. MD was assessed as percent MD (PMD) using a semiautomated method by two readers for every patient. The association of ER/PR and PMD was studied with multifactorial analyses of covariance with PMD as the target variable and including well-known factors that are also associated with MD, such as age, parity, use of hormone replacement therapy, and body mass index (BMI). In addition to the commonly known associations between PMD and age, parity, BMI and hormone replacement therapy, a significant inverse association was found between PMD and ER expression levels. Patients with ER-negative tumors had an average PMD of 38%, whereas patients with high ER expression had a PMD of 35%. A statistical trend toward a positive association between PMD and PR expression was also seen. PMD appears to be inversely associated with ER expression and may correlate positively with PR expression. These effects were independent of other risk factors such as age, BMI, parity, and hormone replacement therapy, possibly suggesting other pathways that mediate this effect.

The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case-control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk inDas Wissen über Brustkrebsrisikofaktoren hat in den letzten 10 Jahren deutlich zugenommen. Insbesondere die Bedeutung von niedrigpenetranten Risikogenen konnte besser verstanden werden. Zusätzlich werden erste Schritte unternommen, um das Zusammenspiel zwischen Umweltfaktoren und genetischen Faktoren besser zu verstehen. Einige genomweite Assoziationsstudien von Fall-Kontroll-Studien und groß angelegte Validierungsstudien konnten mehr als ein Dutzend validierte Single Nucleotid Polymorphismen (SNPs) als genetische Risikofaktoren etablieren. Dabei handelt es sich um Veränderungen in Genen, von denen teilweise bekannt war, dass sie bei der Pathogenese des Mammakarzinoms eine Rolle spielen. Andere dieser Gene waren bislang noch nicht mit der Biologie des Mammakarzinoms in Verbindung gebracht worden. Auch konnten SNPs identifiziert werden, die das Lebenszeitrisiko von BRCA-Mutationsträgern modifizieren können. In Bezug auf nicht genetische Risikofaktoren hat das Wissen um die Hormonersatztherapie (HRT) in den letzten 10 Jahren deutlich zugenommen, sodass eine bessere Nutzen-Risiko-Bewertung vorgenommen werden konnte. Die mammografische Dichte hat sich als wichtiger und akzeptierter Risikofaktor etabliert. Lifestyle und Ernährung werden nach wie vor mit großem Interesse als Risikofaktoren für das Mammakarzinom untersucht. Einige Studien konnten auch auf diesem Gebiet das Wissen erweitern. Mehr als 10 Jahre nach der Publikation der ersten Chemopräventionsstudien gibt es nunmehr nicht nur zur Substanz Tamoxifen Ergebnisse. Auch zu Raloxifen und Aromatasehemmern gibt es Studien, die deren protektive Wirkung nachgewiesen haben. Schließlich wurde in den meisten westlichen Industrieländern das Mammografiescreening als Früherkennung etabliert und bereits jetzt werden Überlegungen unternommen, wie man durch die Integration von individualiserter Risikoprädiktion die Früherkennung verbessern könnte.

Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. Cancer Res; 71(19); 6240–9. ©2011 AACR.

Computer-assisted diagnosis (CADx) for the interactive characterization of mammographic masses as benign or malignant has a high potential to help radiologists during the critical process of diagnostic decision making. By default, the characterization of mammographic masses is performed by extracting features from a region of interest (ROI) depicting the mass. To investigate the influence of a so-called bilateral filter based emph{flat texture} (FT) preprocessing step on the classification performance, textural as well as frequency-based features are calculated in the ROI, in the core of the mass and in the mass margin for preprocessed and unprocessed images. Furthermore. the influence of the parameterization of the bilateral filter on the classification performance is investigated. Additionally, as reference Median and Gaussian filters have been used to compute the FT image and the resulting classification performances of the feature extractors are compared to those obtained with the bilateral filters. Classification is done using a k-NN classifier. The classification performance was evaluated using the area Az under the receiver operating characteristic (ROC) curve. A publicly available mammography database was used as reference image data set. The results show that the proposed FT preprocessing step has a positive influence on the texture-based feature extractors while most of the frequency-based feature extractors perform better on the unprocessed images. For some of the features the original Az could be improved up to 10%. The comparison of the bilateral filter approach with the Median and Gaussian filter approaches showed the superiority of the bilateral filter.

Tumour size estimates using mammography (MG), conventional ultrasound (US), compound imaging (CI) and real-time elastography (RTE) were compared with histopathological specimen sizes.The largest diameters of 97 malignant breast lesions were measured. Two US and CI measurements were made: US1/CI1 (hypoechoic nucleus only) and US2/CI2 (hypoechoic nucleus plus hyperechoic halo). Measurements were compared with histopathological tumour sizes using linear regression and Bland-Altman plots.Size prediction was best with ultrasound (US/CI/RTE: R (2) 0.31-0.36); mammography was poorer (R(2) = 0.19). The most accurate method was US2, while US1 and CI1 were poorest. Bland-Altman plots showed better size estimation with US2, CI2 and RTE, with low variation, while mammography showed greatest variability. Smaller tumours were better assessed than larger ones. CI2 and US2 performed best for ductal tumours and RTE for lobular cancers. Tumour size prediction accuracy did not correlate significantly with breast density, but on MG tumours were more difficult to detect in high-density tissue.The size of ductal tumours is best predicted with US2 and CI2, while for lobular cancers RTE is best. Hyperechoic tumour surroundings should be included in US and CI measurements and RTE used as an additional technique in the clinical staging process.

Traditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival. We evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided. In the hypothesis-generating dataset, SNP rs4778137 (C > G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)). The rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.

Purpose To compare direct magnetic resonance galactography (dMRG) and conventional galactography (CGal). Materials and Methods Thirty women underwent CGal and dMRG. Duct localization and the depth of the assumed underlying pathology in CGal and dMRG were analyzed. Results Comparing CGal and dMRG, there was no significant difference regarding sector localization, but for depth of pathology ( P =.023). Conclusion Duct localization with dMRG was possible with the same reliability as with CGal. Thus, dMRG may have the potential to become an alternative method to CGal.

Calcifying tendonitis is a degenerative inflammatory joint disorder. Pain relief can be successfully achieved with low-dose radiotherapy. It is actually unknown which types of calcifying tendonitis respond to radiotherapy and which do not. The authors tried to get predictive objectives for the response to radiotherapy on the basis of different morphological patterns of calcifications evaluated by X-ray and ultrasound. Between August 1999 and September 2002, a total of 102 patients with 115 painful shoulder joints underwent low-dose radiotherapy. At the beginning of radiotherapy, every shoulder joint was examined with a radiograph in two planes. In addition, sonography was performed before and during therapy. This examination was repeated 6 and 18 months after irradiation. Radiotherapy consisted of two series with a total dose of 6.0 Gy. 29 joints with calcifying tendonitis could be further divided using the sonographic and radiographic classification according to Farin and Gartner, respectively. Pain relief was achieved in 94/115 joints (82%) at a follow-up of 18 months (median). A different response to radiotherapy was found using the sonographic classification of Farin: calcifying tendonitis type III (n = 18) responded well in contrast to a significantly worse result in type I (n = 11). The radiologic classification did not provide a predictive value. Sonographic classification of calcifying tendonitis is predictive for the outcome after radiotherapy. Especially patients with Farin type III calcification will benefit from low-dose radiotherapy.

While screening mammography is accepted as the most adequate technique for the early detection of breast cancer, its low positive predictive value leads to many breast biopsies performed on benign lesions. Therefore, we have previously developed a knowledge-based system for computer-aided diagnosis (CADx) of mammographic lesions. It supports the radiologist in the discrimination of benign and malignant lesions. So far, our approach operates on the lesion level and employs the paradigm of content-based image retrieval (CBIR). Similar lesions with known diagnosis are retrieved automatically from a library of references. However, radiologists base their diagnostic decisions on additional resources, such as related mammographic projections, other modalities (e.g. ultrasound, MRI), and clinical data. Nonetheless, most CADx systems disregard the relation between the craniocaudal (CC) and mediolateral-oblique (MLO) views of conventional mammography. Therefore, we extend our approach to the full case level: (i) Multi-frame features are developed that jointly describe a lesion in different views of mammography. Taking into account the geometric relation between different images, these features can also be extracted from multi-modal data; (ii) the CADx system architecture is extended appropriately; (iii) the CADx system is integrated into the radiology information system (RIS) and the picture archiving and communication system (PACS). Here, the framework for image retrieval in medical applications (IRMA) is used to support access to the patient's health care record. Of particular interest is the application of the proposed CADx system to digital breast tomosynthesis (DBT), which has the potential to succeed digital mammography as the standard technique for breast cancer screening. The proposed system is a natural extension of CADx approaches that integrate only two modalities. However, we are still collecting a large enough database of breast lesions with images from multiple modalities to evaluate the benefits of the proposed approach on.

Digital mammography and comprehensive breast cancer screening approaches have led to the generation of a vast amount of image data. Since the visual inspection of a large set of images is expensive and to some extend also subjective, new methods for fully automated mammography image analysis are needed. The Definiens Cognition Network Technology (CNT) solves the image analysis problem by simulating human cognition processes using knowledge based and context dependent processing. It represents processed image data, image processing methods, and image objects and their definitions in a unified model which incorporates elements from semantic networks, description logics and functional programming. We present first steps towards a successful application of this technology on automated detection of masses and calcifications according to the ACR BI-RADS™ standard.

Die Computerassistierte Diagnose (CAD) in der Mammographie hat durch den europaweiten Aufbau von nationalen Screeningprogrammen in den letzten Jahren stark an Bedeutung gewonnen. Fur die Evaluierung und vor allem fur den Vergleich von CAD Algorithmen sind offentlich zugangliche Referenzdaten notig. Am Fraunhofer IIS wird derzeit eine Referenzdatenbank fur die Mammographie aufgebaut, die die veralteten bestehenden Datenbanken ersetzen bzw. erganzen soll. Dabei wurde auf dem Stand der Geratetechnik entsprechende Bildqualitat und zeitgemase ikonische und textuelle Annotation geachtet. Die Veroffentlichung dieser Referenzdaten wird es Forschungsgruppen erlauben, CAD Algorithmen fur die Mammographie auf umfangreichen und aktuellen Referenzdaten zu evaluieren und ihre Leistungsfahigkeit miteinander zu vergleichen.

This work aims to propose an interactive method for a iconic and textual annotation of digital mammograms. The suggested annotation tool consists of a semantic network to represent all information about a set of mammograms obtained from experts in a structured manner based on the BIRADS standard, a correlated XML file system for persistence, data exchange and storage, and a graphical user interface, allowing a combination of iconic and textual annotation. This approach allows a complete annotation of all findings in a set of mammograms in a structured way, which is also machine readable and interpretable. Thus, systematically annotated image data sets can be used for structured information retrieval as well as case based reasoning systems for computer assisted diagnosis (CAD). Furthermore, such a digital annotation system can be used to replace paper reports and hence avoid unnecessary media breaks during the process of the examination and documentation.

A retrospective clinical-histological study to determine the diagnostic accuracy using high-resolution digital phosphor storage plates (CR) (hardcopy) and full-field digital mammography (DR) (hardcopy) for microcalcifications and focal lesions (BI-RADS category 4 or 5) (n = 100).From 01/2004 to 06/2004, 100 patients underwent digital storage plate mammography (CR) and, after diagnosis and preoperative wire localization, full-field digital mammography (a-Se) (DR) with the same exposure parameters. Five investigators retrospectively determined the diagnosis after the operation from randomly distributed mediolateral views (hardcopy reading). These results were correlated with the final histology.The accuracy of digital storage plate mammography (CR) and full-field digital mammography (DR) was 73% and 76% for all findings (n = 100), 74%, 78% for microcalcifications (n = 50) and 72%, 74% for focal lesions (n = 50). The overall results showed no difference.Our findings indicate equivalence of high-resolution digital phosphor storage plate mammography (CR) and full-field digital mammography (a-Se) (DR).

Objective The growing awareness of female breast cancer has led to increased sensitivity toward pathologic breast conditions in children and adolescents. Thus, approximately 15% of patients in child and adolescent gynecology are referred for the first time because of conspicuous features of the breast such as pain, palpable masses, and other findings on visual inspection. The aim of this study was to analyze the underlying diagnoses and diseases and determine the status of breast sonography in the diagnostic process. Methods The study population consisted of 62 female patients between 8 weeks and 20 years of age (1997-2002) who were examined clinically, followed by standardized sonography (7.5-13 MHz, conventional B-mode panoramic sonography). Presumed diagnoses were confirmed by biopsy in some patients (n = 16) and by follow-up with clinical examination and sonography in most cases (n = 46). Results The clinical and sonographic evaluation confirmed 4 main groups of diagnoses: benign tumors (15), developmental disturbances (14), cystic changes (11), and inherent defects (7). In the remaining cases, the findings were no abnormality (9), nipple discharge without evidence of pathologic or morphologic correlates (3), abscesses (2), and epidermoid cyst (1). Conclusions Knowledge of regular breast development and its variants is essential for the physician. Given knowledge of the sonographic appearance of physiologic breast development and specific lesions, breast sonography is most helpful in identifying and characterizing abnormalities and guiding further investigation.

In order to promote the quality of health care and guidelines in Germany the German Guideline Clearinghouse (Sponsors: German Medical Association, National Association of the Statutory Health Insurance Physicians, German Hospital Federation, Associations of the Sickness Funds and the Statutory Pension Insurance) was established at the Agency for Quality in Medicine (AQuMed) in 1999. The results of the 10th Guideline Clearing Project, the Guideline Clearing Report "Breast Cancer", were published in December 2003. In a systematic search using English/German language guideline databases and literature databases (Medline, Healthstar, Embase), 16 national guidelines were identified which were in accordance to the inclusion criteria (breast cancer treatment; German or English language; published after 1992; new guideline or genuine update (no adaptation); recommended for country-wide implementation). The methodological quality of these 16 guidelines was evaluated using the appraisal instrument of the German Guideline Clearinghouse, the checklist "Methodological Quality of Clinical Practice Guidelines". A peer review of the guidelines was performed by a multidisciplinary focus group of experts (intended guideline users from clinical and ambulatory settings as well as patients). This group consented comments and recommendations for actions of health care policy makers in Germany for a German breast cancer guideline based on examples from the appraised guidelines. None of the identified guidelines contained information about all of the 24 key topics that the focus group considered to be relevant for a German national guideline. The selected exemplary text extracts from the evaluated guidelines can be used as benchmarks and example sources for the development of a national German breast cancer guideline. From the beginning, patients should be involved in the development process within a multidisciplinary team. Due to the rapid emergence of new evidence, oncology guidelines need an effective procedure for updating in order to ensure that they are able to promote health care quality by giving current recommendations based on best available evidence. International networks such as the Guidelines International Network (G-I-N) will be helpful to collect and appraise the evidence for the national guideline development groups in an effective way.

1. Im Rahmen der komplementaren Mammadiagnostik haben interventionelle Methoden wie die sonographisch/mammographisch-stereotaktisch gezielte/gefuhrte Stanz-/Vakuum-/Exzi-sionsbiopsie ihren festen Stellenwert. 2. Mit den transkutanen Biopsiemoglichkeiten stehen minimal-invasive Untersuchungsmethoden zur Verfugung, damit bei histologisch gesicherten benignen Herdbefunden auf eine offene chirurgische Exzision verzichtet werden kann. 3. Unter Beachtung strenger Kriterien ist dies ein Weg, die Spezifitat und den negativen Vorhersagewert der komplementaren Mammadiagnostik zu verbessern. 4. Transkutane Biopsiemethoden sind kostengtinstiger, zeitsparender und mit geringerer Morbiditat belastet als ein operativer Eingriff.

Until recently, for mammography Mo anode-Mo filter x-ray tube assemblies were almost exclusively used. Modern mammography units provide the possibility to employ a variety of anode-filter combinations with the aim of adapting the x-ray spectrum to compressed breast thickness and composition. The present contribution provides information on the radiation exposure of two large groups of patients (one of 1678 and one of 945 women) who were mammographed with modern x-ray equipment, and on the dosimetry necessary for the evaluation. For dosimetric purposes spectral information is essential. X-ray spectra have been determined for various anode-filter combinations from measurements with a Ge detector. Based on these spectra, conversion factors from air kerma free in air to average glandular dose (g factors) have been calculated for different anode-filter combinations, compressed breast thickness ranging from 2 to 9 cm and breast compositions varying from 0 to 100% glandular tissue. Determinations of various quantities, including entrance surface air kerma (ESAK), tube output, tube loading (TL), fraction of glandular tissue (FGL) and compressed breast thickness, were made during actual mammography. Average glandular dose (AGD) was determined using g factors corrected for tissue composition as well as g values for standard breast composition, i.e. 50% adipose tissue and 50% glandular tissue by mass. It is shown that, on average, the influence of the actual breast composition causes variations of the order of about 15%. For group 1 and group 2, the mean values of average glandular dose (using g factors corrected for tissue composition) were 1.59 and 2.07 mGy respectively. The number of exposures per woman was on average 3.4 and 3.6 respectively. The mean value of compressed breast thickness was 55.9 and 50.8 mm respectively. The mean age of group 1 was 53.6 years (for group 2 the age was not recorded). The fraction by mass of glandular tissue FGL decrease with increasing compressed breast thickness and age of patient (from 75% at 25 mm to 20% at 80 mm, and from 65% at 20 years to 30% at 75 years). For a medium-sized breast, i.e. a compressed breast thickness of 55 mm, FGL is about 35%, indicating that the standard mix (FGL = 50%) might need some modification, particularly because of additional evidence from another investigation with similar results on FGL.

Background: Clinical evidence for the anticancer activity of adjuvant zoledronic acid (ZOL) in patients with early stage breast cancer (BC) has been reported in several randomized clinical trials including ZO-FAST, AZURE (>5 yr postmenopausal subset), and ABCSG-12. In addition, combining ZOL with standard neoadjuvant therapy improved pathologic complete response (pCR) and reduced the need for mastectomy in the AZURE trial. The open-label, multicenter, phase 2, FEMZONE trial examined the effect of neoadjuvant letrozole (LET) ± ZOL on tumor response in postmenopausal patients with hormone receptor-positive (HR+) primary BC. Here, we report the efficacy and safety after 6 mo of treatment. Methods: Postmenopausal women with HR+ BC and ECOG performance status of 0–2 were randomized to LET (2.5 mg/d) ± ZOL (4 mg q4w). The primary efficacy endpoint was objective response rate (ORR; complete + partial response per RECIST criteria) at 6 mo by central review. Secondary endpoints included ORR in the per-protocol and safety populations, best response, breast-conserving surgery, pCR, change in tumor size, overall survival, and safety. Between-group differences in ORR were evaluated using Fisher's exact test. Results: Among enrolled patients (N = 168; mean age 70.9 yr; mean treatment duration 6.5 mo), patients receiving LET + ZOL experienced numerically better ORR at 6 mo versus LET alone (69.2% vs 54.5%, respectively), with a between-group difference of 14.7% (P = .106). Although the primary endpoint did not reach statistical significance because of insufficient patient recruitment, the prespecified between-group difference of ≥10% was met. A similar trend in ORR at 6 mo favoring ZOL was also seen by local assessment (Δ11%, P = .192). At 4 mo, higher ORR was observed for LET + ZOL versus LET alone both for the local (33.3% vs 24%, respectively) and central assessments (41.5% vs 30.3%, respectively). Numerically more patients receiving LET + ZOL experienced a partial response at 6 mo versus LET alone (66.2% vs 54.5%, respectively). At 6 mo, the mean tumor size had decreased from 3.34 ± 1.98 cm to 2.1 ± 1.76 cm in the overall patient population, and the decrease was slightly larger with LET + ZOL compared with LET alone (–1.37 ± 0.96 cm vs −1.12 ± 0.92 cm, respectively). Overall, there was no difference in the number of patients requiring mastectomy between LET + ZOL and LET alone (15.6% vs 15.2%, respectively). Incidence of adverse events (AEs) was slightly higher among patients receiving LET + ZOL versus LET alone (92.1% vs 81%, respectively), and the types of AEs were consistent with the known safety profiles of these agents. No deaths or osteonecrosis of the jaw was reported during the course of the study. Conclusions: This study provides additional confirmation of the efficacy of LET as neoadjuvant therapy for early HR+ BC, and supports previous reports of ZOL's anticancer activity in this setting (as evidenced by the trend toward improved ORR with ZOL + LET versus LET alone). These data, together with other published ZOL studies, suggest that adding ZOL to neoadjuvant therapy may be considered for postmenopausal patients scheduled to receive neoadjuvant endocrine therapy for BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-02.

Introduction: Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design.Methods: A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model.Results: Of the 470 image- analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model.Conclusions: Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy.