Breast Neoplasms: Schmutzler R

Albert US, Altland H, Duda V, Engel J, Geraedts M, Heywang-Köbrunner S, Hölzel D, Kalbheim E, Koller M, König K, Kreienberg R, Kühn T, Lebeau A, Nass-Griegoleit I, Schlake W, Schmutzler R, Schreer I, Schulte H, Schulz-Wendtland R, Wagner U, Kopp I. · Faculty of Medicine, Philipps-University, Marburg, Germany. · J Cancer Res Clin Oncol. · Pubmed #18661152 No free full text.

Abstract: INTRODUCTION: The goal of the 2008 updated guideline: early detection of breast cancer in Germany is to support physicians as well as healthy and affected women in the decision-making process involved in the diagnostic chain for the early detection of breast cancer by providing them with evidence- and consensus-based recommendations. The updated guideline replaces the guideline issued in 2003. MATERIALS AND METHODS: The guideline forms the basis for developing an effective and efficient national early breast cancer detection program that meets the standards set by the Council of Europe and WHO for cancer control programs. The guideline presents the current, evidence- and consensus-based state of scientific knowledge in a multidisciplinary approach for the entire diagnostic chain, consisting of history taking and risk consultation, information on health behavior, clinical breast examination, diagnostic imaging, image-guided percutaneous tissue-acquisition techniques, open surgical excisional biopsy and pathomorphological tissue evaluation. The guideline recommends a set of quality indicators to assure resource availability, performance quality and outcomes enhancing total quality management for early breast cancer diagnosis. CONCLUSION: Currently, early detection of breast cancer offers the most promising possibility to optimize the diagnosis and treatment of breast cancer and, as a result, reduce breast cancer mortality and improve health related quality of life in women.

Albert US, Altland H, Duda V, Engel J, Geraedts M, Heywang-Köbrunner S, Hölzel D, Kalbheim E, Koller M, König K, Kreienberg R, Kühn T, Lebeau A, Nass-Griegoleit I, Schlake W, Schmutzler R, Schreer I, Schulte H, Schulz-Wendtland R, Wagner U, Kopp I. · Planungskommission und Arbeitsgruppenleiter der Konzertierten Aktion Brustkrebs-Früherkennung in Deutschland, Deutschland. · Chirurg. · Pubmed #18463837 No free full text.

Abstract: The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline's recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.

Albert US, Altland H, Duda V, Engel J, Geraedts M, Heywang-Köbrunner S, Hölzel D, Kalbheim E, Koller M, König K, Kreienberg R, Kühn T, Lebeau A, Nass-Griegoleit I, Schlake W, Schmutzler R, Schreer I, Schulte H, Schulz-Wendtland R, Wagner U, Kopp I. · Planungskommission und Arbeitsgruppenleiter der Konzertierten Aktion Brustkrebs-Früherkennung in Deutschland. · Rofo. · Pubmed #18438746 No free full text.

This publication has no abstract.

Schmutzler R, Schlegelberger B, Meindl A, Gerber WD, Kiechle M, Anonymous00116. · Technische Universität München, Frauenklinik rechts der Isar, Munich. · Zentralbl Gynakol. · Pubmed #14755360 No free full text.

Abstract: Women with familial predisposition for breast and ovarian cancer represent a small group of patients with very high risk for developing breast and/ or ovarian cancer before the age of 50 years. The individual breast cancer risk can be assessed by genetic counselling and can be specified by genetic diagnostics. As part of the gynaecological consultation, adequate preventive measures are offered. Psycho-oncological counselling may help in decision making. For hereditary carcinomas, counselling is still not considered as a routine medical care, even though basic and routine preventive measures are insufficient for this group of high risk patients. Within the last years, 12 specialized centres in Germany have developed a patient care concept for women with a familial risk for breast and ovarian cancer. Establishment of these centres for familial breast and ovarian cancer and use of evidence-based medical care was initiated in a nationwide interdisciplinary joint research project and supported by the German Cancer AiD. These measures were integrated in a quality assurance concept for structure, process and result optimization. Thus, all requirements for introducing these services into routine patient management have been fulfilled.

Schlehe B, Schmutzler R. · Universitätsfrauenklinik, Vossstrasse 9, 69115, Heidelberg. · Chirurg. · Pubmed #18854964 No free full text.

Abstract: Ten per cent of all breast cancer cases have a strong hereditary component in which half carry a deleterious mutation in the high penetrance genes BRCA1 or BRCA2. These genes confer a lifetime risk of 60-80% for breast cancer and 20-40% for ovarian cancer. Since the identification of these genes in the mid-1990s, an interdisciplinary approach was established in 12 specialized university-based centres in Germany for identifying high-risk families that enables genetic testing and preventive clinical options. It could be demonstrated that ultrasound, mammography, and breast MRI allow the identification of early breast cancer stages. Prophylactic mastectomy and salpingo-oophorectomy reduce breast and ovarian cancer incidence considerably. New therapeutic and preventive strategies are being validated in ongoing clinical studies. Most recently a new molecular target, a PARP inhibitor, was developed that targets specifically BRCA-deficient tumour cells. Participation in a phase II study for metastatic breast and ovarian cancer is available through the centres. Accompanying scientific studies of over 4,500 DNA samples from BRCA1/2-negative high-risk families are moreover being examined for other predisposing genes.

Von Minckwitz G, Costa SD, Brunnert K, Dall P, Nitz U, Diel I, Fersis N, Friedrich M, Friedrichs K, Thomssen Ch, Gerber B, Göhring UJ, Harbeck N, Hanf V, Schaller G, Scharl A, Schmutzler R, Simon WE, Untch M, Anonymous00148. · Universitäts-Frauenklinik Frankfurt, Germany. · Zentralbl Gynakol. · Pubmed #12232813 No free full text.

This publication has no abstract.

Sadr-Nabavi A, Ramser J, Volkmann J, Naehrig J, Wiesmann F, Betz B, Hellebrand H, Engert S, Seitz S, Kreutzfeld R, Sasaki T, Arnold N, Schmutzler R, Kiechle M, Niederacher D, Harbeck N, Dahl E, Meindl A. · Department of Obstetrics and Gynecology, Technische Universitaet Muenchen, Munich, Germany. · Int J Cancer. · Pubmed #19115204 No free full text.

Abstract: EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1) was recently described as an antagonist of angiogenesis. Motivated by a strong dependence of tumor growth and metastasis on angiogenesis, we investigated the role of EFEMP1 in human breast cancer. We applied RNA microarray expression analysis and quantitative real-time PCR (QRT) in a total of 45 sporadic breast cancer tissues and found EFEMP1 down-regulation in 59% and 61% of the analyzed tissues, respectively. This down-regulation was confirmed on protein level. Immunohistochemistry in 211 breast cancer tissues resulted in reduced or even abolished EFEMP1 expression in 57-62.5% of the tumors. Bisulphite genomic sequencing in breast cancer cell lines and primary breast cancer tissues revealed promoter methylation as the major cause of this down-regulation. Furthermore, analysis of 203 clinically well characterized primary breast cancers displayed a significant correlation of reduced EFEMP1 protein expression with poor disease-free (p = 0.037) and overall survival (p = 0.032), particularly in those node-positive patients who received adjuvant anthracycline-based chemotherapy, but not in those treated by either cyclophosphamide-methotrexate-5-fluorouracil (CMF) or Tamoxifen. In summary, the presented data demonstrate for the first time the reduced EFEMP1 expression on RNA and protein level in a substantial number of sporadic breast carcinomas and its correlation with epigenetic alterations. Furthermore, these data point towards a possible predictive impact of EFEMP1 expression in primary breast cancer.

Klein A, Olendrowitz C, Schmutzler R, Hampl J, Schlag PM, Maass N, Arnold N, Wessel R, Ramser J, Meindl A, Scherneck S, Seitz S. · Institute of Molecular Biology and Bioinformatics, Charité, Campus Benjamin Franklin, Arnimalle 22, Berlin, Germany. · Cancer Lett. · Pubmed #19114293 No free full text.

Abstract: In breast cancer, metastases are relatively widely distributed, with the most common sites being bone, regional lymph nodes, lung, liver, and brain. The detailed mechanism of organ-specific metastasis is poorly understood. In this study, we initiated a search for genes that are implicated in brain or bone metastasis of primary human breast cancer. We generated gene expression profiles of 18 brain and eight bone metastases derived from primary breast tumors. We identified 73 genes differentially expressed between brain and bone metastases. Visualization of the differential gene expression profiles by correspondence and cluster analyses shows that the metastases clearly separate into two distinct groups as an exact reflection of their site of metastasis. Moreover, the analysis of this gene set in primary breast tumors relapsing to either bone or brain allowed accurate categorization of the tumors according to their metastatic site. The identified genes may prove to be excellent markers to predict the site of metastasis in breast cancer patients and could lead to tailor-made therapy to an individual patient.

Couch FJ, Sinilnikova O, Vierkant RA, Pankratz VS, Fredericksen ZS, Stoppa-Lyonnet D, Coupier I, Hughes D, Hardouin A, Berthet P, Peock S, Cook M, Baynes C, Hodgson S, Morrison PJ, Porteous ME, Jakubowska A, Lubinski J, Gronwald J, Spurdle AB, Anonymous00430, Schmutzler R, Versmold B, Engel C, Meindl A, Sutter C, Horst J, Schaefer D, Offit K, Kirchhoff T, Andrulis IL, Ilyushik E, Glendon G, Devilee P, Vreeswijk MP, Vasen HF, Borg A, Backenhorn K, Struewing JP, Greene MH, Neuhausen SL, Rebbeck TR, Nathanson K, Domchek S, Wagner T, Garber JE, Szabo C, Zikan M, Foretova L, Olson JE, Sellers TA, Lindor N, Nevanlinna H, Tommiska J, Aittomaki K, Hamann U, Rashid MU, Torres D, Simard J, Durocher F, Guenard F, Lynch HT, Isaacs C, Weitzel J, Olopade OI, Narod S, Daly MB, Godwin AK, Tomlinson G, Easton DF, Chenevix-Trench G, Antoniou AC, Anonymous00431. · Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #17627006 links to  free full text

Abstract: The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.

Klein A, Wessel R, Graessmann M, Jürgens M, Petersen I, Schmutzler R, Niederacher D, Arnold N, Meindl A, Scherneck S, Seitz S, Graessmann A. · Institute of Molecular Biology and Bioinformatics, Charité, Campus Benjamin Franklin, Berlin, Germany. · Int J Cancer. · Pubmed #17410534 No free full text.

Abstract: The aim of our work was to establish a database for breast cancer gene expression data in order to compare human and mouse breast cancer. We identified human and mouse homologues genes and compared the expression profile of 24 human breast tumors with 6 WAP-SVT/t breast tumors (WAP-SVT/t animals, line 8). Our studies confirmed the heterogeneity in gene expression of human as well as mouse breast cancer cells. However, 63 genes were found to be differentially expressed (upregulated: 40; downregulated: 23 genes) in at least 75% of the breast tumors of both species. To differentiate between early and late events in tumor formation, we compared the 63 differentially expressed genes with a mouse data set obtained from hyperplastic mammary glands. This revealed that the majority of the early deregulated genes are cell proliferation specific. These early changes seem to be necessary although not sufficient for breast cancer formation. Late alterations concern mainly genes belonging to the category of cell communication and metabolism. Interestingly, most of the 63 conserved genes are commonly associated with tumorigenesis.

Dahl E, Sadr-Nabavi A, Klopocki E, Betz B, Grube S, Kreutzfeld R, Himmelfarb M, An HX, Gelling S, Klaman I, Hinzmann B, Kristiansen G, Grützmann R, Kuner R, Petschke B, Rhiem K, Wiechen K, Sers C, Wiestler O, Schneider A, Höfler H, Nährig J, Dietel M, Schäfer R, Rosenthal A, Schmutzler R, Dürst M, Meindl A, Niederacher D. · Institute of Pathology, RWTH Aachen, Germany. · J Pathol. · Pubmed #15586368 No free full text.

Abstract: The identification of novel disease-associated genes in gynaecological tumours has important implications for understanding the process of tumourigenesis and the development of novel treatment regimens. cDNA libraries from disease tissues may represent a valuable source to identify such genes. Recently, a bio-informatic procedure based on an 'electronic Northern' approach was established to screen expressed sequence tag (EST) libraries for genes differentially expressed in tumour and normal tissues, and identified 450 candidate genes differentially expressed in breast and ovarian cancer. In this report, the validation of an initial set of 40 candidate genes, which were selected due to their localization in chromosomal regions frequently altered in gynaecological tumours, is described. Differential expression of 29 of these genes, including three uncharacterized novel genes, was confirmed by applying cancer profiling arrays with 106 matched pairs of tumour/normal cDNAs and quantitative reverse transcription-polymerase chain reaction (RT-PCR) on 60 clinical specimens. The majority of these differentially expressed genes have not been described previously in the context of breast and ovarian cancer, and may constitute novel diagnostic markers for these tumour entities.

Seitz S, Frege R, Jacobsen A, Weimer J, Arnold W, von Haefen C, Niederacher D, Schmutzler R, Arnold N, Scherneck S. · Department of Tumor Genetics, Max Delbrueck Center for Molecular Medicine, Robert Roessle Str. 10, 13125 Berlin, Germany. · Oncogene. · Pubmed #15580292 No free full text.

Abstract: Several investigations have supposed that tumor suppressor genes might be located on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression analysis identified a set of 109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are differentially expressed in human breast tumors. The expression pattern of CT8-ps was associated with prognostic factors such as tumor size and grading as well as loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer.

Morakkabati-Spitz N, Sondermann E, Schmiedel A, Leutner C, Riehm K, Schmutzler R, Schild H, Kuhl CK. · Radiologische Universitätsklinik Bonn. · Rofo. · Pubmed #12584619 No free full text.

Abstract: PURPOSE: To analyze prevalence and type of relevant incidental findings in patients undergoing breast MRI. MATERIALS AND METHODS: This prospective investigation consists of 1013 patients who underwent breast MRI as follow-up after breast cancer therapy, for pre-operative staging, and for screening of high-risk patients as well as for clarification of unclear clinical examinations and inconclusive conventional mammography. Prevalence and type of relevant incidental extramammary findings were recorded together with the indication of the examination. RESULTS: Incidental extramammary findings were encountered in 92 (9%) of the 1013 patients. MRI had markedly more incidental extramammary findings with the staging examinations (39.5%) and follow-up examinations (11.6%). The prevalence of incidental malignant findings was 81% in patients examined for pre-operative staging. Incidental benign and malignant findings were equally frequent in patients followed after breast cancer therapy. The incidental findings were exclusively benign in patients without a history of breast cancer. CONCLUSION: The interpretation of breast MRI should incorporate a careful analysis of the adjacent extramammary structures. Especially patients followed after breast cancer therapy can be expected to have incidental malignant findings outside the breast.

Kiechle M, Schmutzler R. · Frauenklinik, Technischen Universität München. · Radiologe. · Pubmed #11388058 No free full text.

Abstract: First retrospective data show that hereditary Breast cancer risk can be positively influenced by prophylactic surgical procedures and hereby a thorough consultation seem to be an option for mutant gene carriers. A first evaluation of the women of 1050 high-risk families by the German Consortium "Hereditary Breast and Ovarian Cancer promoted by the German Cancer Aid (Deutsche Krebshilfe)" has shown that approximately 80% of the women concerned decide to participate in an intensive early detection--programme and only 5% of the women have decided to submit themselves to prophylactic surgical measures. This again shows how absolutely necessary the elaboration and evaluation of early detection measures within the different investigation projects are.

Hofmann W, Wappenschmidt B, Berhane S, Schmutzler R, Scherneck S. · No affiliation provided · J Med Genet. · Pubmed #12114493 links to  free full text

This publication has no abstract.