Breast Neoplasms: Wagner U

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.

Seifart U, Albert US, Heim ME, Hübner J, Jungkunz W, Prokein R, Rick O, Hoffmann M, Engenhart-Cabillic R, Kopp I, Wagner U, Kalder M. · Hamm-Kliniken, Bad Soden-Salmünster. · Rehabilitation (Stuttg). · Pubmed #18188805 No free full text.

Abstract: Secondary lymphedema is one of the most frequent long-term side effects affecting up to 30% of all breast cancer patients after local surgical and radiation treatment. Destruction of the lymphatic system causes a progressive and chronic condition with functional impairments and disabilities limiting patients in their daily activities and involving nearly all aspects of their quality of life. Also, problems in the occupational area may be caused by lymphedema. The need for improving oncological management for early diagnosis and referral for effective treatment of lymphedema is a major goal of breast cancer heath care while survival improves. METHOD: A systematic consensus process was performed involving all relevant partners and providers of lymphedema health care to develop a practical documentation concept and make recommendations according to the evidence of clinical studies and currently available guidelines. RESULTS: A practical concept of documentation with defined assessment points was developed for evaluation and monitoring of lymphedema, which included the assessment of quality of life parameters with recognised instruments by the patient themselves. Consensus recommendations for the postoperative management, prevention, treatment and follow-up of breast cancer patients along a clinical algorithm for in- and outpatient care were finalized. CONCLUSION: With improved survival, long-term side effects with major impact on quality of life become a most important end point criteria of oncological treatment. The clearly defined documentation concept and the comprehensive recommendations for lymphedema management may assist clinicians and patients to make timely decisions about in- and outpatient health care practice to optimize the interface between acute medicine and rehabilitation. Patients' compliance with treatment and prevention routines will be as important as ensuring the continuity of care. A longitudinal prospective study evaluating the effectiveness and efficacy of the consensus recommendation is currently being implemented.

Bock K, Hadji P, Duda VF, Jackisch C, Wagner U. · Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie der Philipps-Unversität Marburg. · Zentralbl Gynakol. · Pubmed #16037902 No free full text.

Abstract: Higher breast density leads to a higher risk of breast-cancer coming along with a reduced sensitivity of mammography, the most important method for early diagnosis of breast cancer. HRT leads to an increase in breast density in up to (1/3) of treated women. Combined regimes of estrogen-progestin show a stronger influence than estrogen only. Changes of breast density appear almost entirely within the first year of administration and seem to be reversible after suspension of treatment within a few weeks. A possible solution of the dilemma is to perform mammography in asymptomatic premenopausal women during the first half of the menstrual cycle. In women with increased breast density using HRT it is recommended to modify the combination of hormones, change the application mode, or suspend HRT for a short period of 3 weeks prior to mammography. In symptomatic women with dense breasts, additive breast ultrasound is strongly recommended to reduce the otherwise high rate of missed breast cancers.

Wagner U, Köhler S, Prietl G, Giffels P, Schmidt-Nicolai S, Schlebusch H, Grünn U, Bender H, Biersack HJ, De Potter C, Krebs D, Wallwiener D. · Universitäts-Frauenklinik, Bonn. · Zentralbl Gynakol. · Pubmed #10355096 No free full text.

Abstract: Anti-idiotypic antibodies, which imitate a tumor-associated antigen by their variable region, offer an elegant method for the induction of a specific immune response, when used as a surrogate antigen for immunization. We generated anti-idiotypic antibodies imitating 2 different tumor-associated antigens. I. CA125 for ovarian carcinomas and II. 14C5, a tumor-associated cell substrate adhesion molecule on breast cancer cells, whereas the first approach could be introduced in a first clinical trial and the second was evaluated in an immunocompetent animal model. For the induction of an immune response against CA125, 18 patients with advanced ovarian cancer (n = 6) or heavily pretreated recurrences (n = 12) were immunized with the anti-idiotypic antibody MAb ACA125. Patients were treated with 2 mg anti-idiotype antibody every two weeks for 4 injections i.m. and then monthly. 12 of 18 patients demonstrated an anti-anti-idiotypic (Ab3) response, which was to a lower extent also directed against CA125 and 9 of 18 patients developed a CA125 specific cellular immune response by their peripheral blood lymphocytes. Based on this data a follow-up clinical trial in advanced ovarian cancer patients with minimal residual disease in an adjuvant approach after primary therapy was started to evaluate the effect of the immune response on the progression free survival. For immunotherapy of breast cancer, we generated a murine monoclonal anti-idiotypic antibody (MAb ACA14C5), which imitates a cell substrate adhesion molecule on breast cancer cells. The anti-idiotype was introduced in an immunocompetent animal to prove his capability on induction of an immune and tumor response. The results showed a highly significant difference in the tumor growth of the ACA14C5 treated group in contrast to the controls starting the immunization on day 6 after tumor cell application with 10 of 12 animals being cured from their tumor burden. Prophylactic immunization against the invasion antigen of breast cancer by anti-idiotypic antibodies showed protection against increasing tumor burden. However, in the situation of established tumors only minor responses could be detected. Vaccination with anti-idiotypic antibodies comprises an effective method for induction of a specific immune response against non-immunogenic tumor-associated antigens and should be therefore considered in immunological approaches to tumor therapy, where the primary structure and sequence of the antigen, e.g. CA125, is up to now not available.

Ziller V, Kalder M, Albert US, Holzhauer W, Ziller M, Wagner U, Hadji P. · Department of Gynaecology, Gynaecological Endocrinology and Oncology, Philipps-University of Marburg, Marburg, Germany. · Ann Oncol. · Pubmed #19150950 No free full text.

Abstract: BACKGROUND: The level of adherence of various pharmacological therapies in chronic diseases varies, but is predominantly low. With tamoxifen (TAM), 23% and 50% nonadherence after 1 and 4 years have been reported. Day-to-day clinical observation suggests that adherence may even be lower with aromatase inhibitors, but limited data exist on the situation in daily clinical routine. The aim of this study was to evaluate the rate of adherent patients in a randomly selected sample of postmenopausal women with primary breast cancer, who had been assigned to an adjuvant endocrine treatment with TAM or anastrozole (ANA). MATERIALS AND METHODS: We investigated a random sample of 100 postmenopausal women with breast cancer (50 TAM and 50 ANA) who had received surgery for their primary breast cancer at our hospital in 2004/2005 and thereafter had been assigned to an adjuvant endocrine treatment. We evaluated the adherence rate with a detailed questionnaire and additionally carried out a retrospective prescription check of the hospital chart as well as calling the local physicians of our patients. A patient was counted as adherent with a self-reported tablet intake of 80% or more and if a medication possession ratio of 80% or more was achieved. RESULTS: Regarding the baseline characteristics, a significant difference in mean age was noticed in women on ANA versus TAM [65 (+/-3) and 72 (+/-3); P<0.001]. All women on TAM and ANA reported to be adherent (100%). After controlling for prescriptions, only 40 (80%) and 27 (69%) of the women on TAM and ANA were still classified as adherent (P<0.01 and P<0.01 versus self-report). We found no significant correlation of adherence to any baseline characteristics or side-effects in a logistic regression model. CONCLUSIONS: An important goal of any therapeutic intervention is to achieve comparable efficacy in routine clinical practice to that demonstrated in randomised clinical trials. However, a similar magnitude of adherence will be necessary in routine clinical practice to assure comparable clinical effects. Our results further support the data on suboptimal adherence of women with breast cancer on adjuvant TAM treatment. Here, we evaluated for the first time the patient reported and real-world adherence on adjuvant ANA and were able to show a similarly low adherence compared with TAM. More prospective studies are needed to increase our understanding of the underlying reasons for nonadherence in women with breast cancer.

Tapia C, Savic S, Wagner U, Schönegg R, Novotny H, Grilli B, Herzog M, Barascud AD, Zlobec I, Cathomas G, Terracciano L, Feichter G, Bubendorf L. · University Department of Pathology of Basel and Baselland, Institute for Pathology, Schönbeinstrasse 40, Basel, 4003, Switzerland. · Breast Cancer Res. · Pubmed #17511881 links to  free full text

Abstract: INTRODUCTION: The status of the gene encoding human EGF-like receptor 2 (HER2) is an important prognostic and predictive marker in breast cancer. Only breast cancers with HER2 amplification respond to the targeted therapy with trastuzumab. It is controversial to what degree the primary tumour is representative of distant metastases in terms of HER2 status. Discrepancies in HER2 status between primary tumours and distant metastases have been described, but their reasons remain unclear. Here, we compared HER2 status on cytological specimens of distant metastases with the result from the primary carcinomas, and explored the prevalence of and the reasons for discrepant results. METHODS: HER2 status was determined by fluorescence in situ hybridisation. HER2 gene amplification was defined as a HER2/chromosome 17 signal ratio of 2 or more. HER2 results from cytological specimens of matched distant metastases were compared with the results from the corresponding primary tumours (n = 105 patients). In addition, lymph node metastases were analysed in 31 of these patients. RESULTS: HER2 amplification was found in 20% of distant metastases. HER2 status was discordant between the primary tumour and distant metastasis in 7.6% of the 105 patients. Re-evaluation revealed that in five patients (4.7%), discrepancies were due to interpretational difficulties. In two of these patients, focal amplification had initially been overlooked as a result of heterogeneity in the primary tumours or in the metastases, respectively. A further three patients had borderline amplification with a ratio close to 2. Discrepancy remained unexplained in three patients (2.9%). CONCLUSION: HER2 gene status remains highly conserved as breast cancers metastasise. However, discrepant results do occur because of interpretational difficulties and heterogeneity of HER2 amplification. Cytological specimens from distant metastases are well suited for HER2 fluorescence in situ hybridisation analysis.

Hadji P, Gottschalk M, Ziller V, Kalder M, Jackisch C, Wagner U. · Philipps University of Marburg, Department of Gynaecology, Gynaecological Oncology and Endocrinology, Pilgrimstein 3, D-35037 Marburg, Germany. · Maturitas. · Pubmed #17049767 No free full text.

Abstract: BACKGROUND: Recent studies suggest an inverse relation between breast cancer and osteoporosis. Oestrogen is important in the pathophysiology of both breast and bone, and although cumulative exposure to oestrogen may explain the link between breast cancer and bone mass, this has never been proved. The Marburg breast cancer and osteoporosis trial (MABOT) aimed to elucidate the relation between breast cancer and bone mass ascertained by ultrasonometry measurement and to investigate whether endogenous and exogenous exposure to oestrogen and reproductive correlates has a role in this association. METHODS: We performed a case-control study including 2492 women (mean age+/-S.D., 54.4+/-10.3 years) in whom diseases and drug treatments known to affect bone metabolism, except for HT, had been excluded. All women underwent ultrasonometry measurement at the heel; 242 of the women had an incident breast cancer without a prior, specific pharmacological breast cancer treatment. The ultrasonometry variables - speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) - were calculated and compared in women with and without breast cancer. Because of significant intergroup differences in factors such as age, body mass index and exposure to oestrogen, a multiple linear regression analysis as well as a second analysis of ultrasonometry variables was undertaken using a randomly selected sample of 242 healthy women post-matched with the breast cancer group for possible confounding variables. Odds ratios were used to compare the relation between breast cancer risk and ultrasonometry heel measurements. RESULTS: Women with breast cancer were significantly older, weighed more, had a higher body mass index, were more likely to be parous and to have breast fed, were older at the menopause and had been exposed to oestrogen for longer than control women. In addition, the ultrasonometry variables speed of sound and the stiffness index T- and Z-score were significantly higher in women with breast cancer even after a matched pair analysis was performed (p<0.001). Additionally, results of a multiple linear regression showed that women with breast cancer had a significantly higher SOS (p<0.001), body weight (p<0.05) and duration of breast feeding (p<0.05) while osteoporotic fracture were reduced (p<0.001). When women with breast cancer and their matched controls were finally grouped according to SOS and T-score quartiles, the odds ratios (95% confidence intervals) for breast cancer risk in the second, third and fourth quartiles compared with the lowest quartile were 2.5 (1.4-4.3), 3.1 (1.8-5.3) and 4.7 (2.7-8.2) as well as 1.9 (1.1-3.2), 2.3 (1.3-3.9) and 2.9 (1.7-5.0), respectively. CONCLUSIONS: The ultrasonometry variables speed of sound, stiffness index, T- and Z-score are higher in women with an incident breast cancer than in healthy controls, even after post-matching for possible confounding variables. This association was confirmed in a multiple linear regression model. Women with SOS and T-score values in the higher quartiles have a greater risk of breast cancer than women in the lowest quartile. We found no association between the higher ultrasonometry variables and cancer specific characteristics or reproductive correlates such as age at menarche and menopause or cumulative oestrogen exposure. Although the biological mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than reproductive correlates, endogenous and exogenous exposure to oestrogen must play a part.

Eggenschwiler J, Patrignani A, Wagner U, Rehrauer H, Schlapbach R, Rist L, Ramos MH, Viviani A. · HSW, Hochschule Wädenswil, Wädenswil, Switzerland. · Arzneimittelforschung. · Pubmed #16927530 No free full text.

Abstract: Cytotoxicity assays in vitro (MTT test) showed that the different breast cancer cell lines Kpl-1, MCF-7 and Mfm-223 respond differently to the mistletoe (Viscum album L.) preparations Iscador. Quercus (Qu), Abies (A), Malus (M) and Pinus (P). In order to determine the differences in the responsiveness of the cells more exactly, the gene expression profiles were determined by cells, which were treated with Mistletoe extracts, compared with untreated control cells. Such differences can be analysed in more detail by looking at the gene expression using Human Whole Genome microarray chips (41,000 genes). The results of the transcriptome analyses suggested that Iscador preparations influenced the overregulation of genes regarding immune defense, stress response, apoptosis and cell-cell adhesion pathways. Within the Mfm-223-Zellen was the Genexpression in MCF-7 and Kpl-1. The MCF-7 cells were affected on the genes which are involved in cell-cell contacts whereas Kpl-1 responded to the mistletoe extracts by changing the mRNA levels of the immune and stress response pathways. Concerning the effects of the mistletoe extract, we conclude that Iscador Qu and M have a greater influence on the immune defense and stress response genes whereas Iscador A tends to affect the cell-cell adhesion and cytoskeleton pathways. In summary, cDNA microarray analyses give us information on whether a cancer cell is sensitive to mistletoe extracts in relation to how many genes are significantly overrepresented after mistletoe treatment, and whether a particular mistletoe extract is more effective on a specific cancer cell than the other preparation.

Albert US, Koller M, Kopp I, Lorenz W, Schulz KD, Wagner U. · Gynecology, Gynecological Endocrinology and Oncology, University of Marburg, Faculty of Medicine, Pilgrimstein 3, Marburg, D-35037, Germany. · Breast Cancer Res Treat. · Pubmed #16710790 No free full text.

Abstract: OBJECTIVES: Improvements in the life expectancy of women with breast cancer raise important questions how to improve quality of life (QoL) for women sustaining complications and side effects of cancer treatment. The presented study examined the prevalence of arm morbidity in a cohort of primary breast cancer patients over time as a result of the extent of axillary lymph node dissection. Of particular interest is the question of using a recognized QoL assessment instrument at defined assessment points as an endpoint criteria of oncological treatment. METHODS: A prospective, population-based, longitudinal cohort study of patients with primary breast cancer was performed (n = 389). QoL data (EORTC QLQ C30 + BR23) and clinical data were assessed at designated time points. Primary endpoint of this analysis was patient reported arm morbidity assessed with the three-idem scale in the BR 23 (swelling, moving, pain). RESULTS: 20% of the patients evidenced considerable impairments in arm functioning. Arm morbidity was significantly related to the number of lymph nodes dissected (P < 0.002 entire cohort, P < 0.001 lymph node negatives) and was independent of age, stage of the disease, kind of breast surgery and radiation treatment. Early impairments in arm functioning (below 50 score values) assessed within 6 months after axillary surgery was a good predictor for late arm morbidity at 12 months RR 11.5 (CI 95% 4.7-28.4), 24 months RR 6.0 (CI95% 2.8-13.3) and 36 months RR 3.8 (CI 95% 1.8-7.9). CONCLUSIONS: Arm morbidity after axillary surgery is a severe and chronic condition affecting many breast cancer patients. The recognized QoL assessment instrument depict patients with severe impairments in arm functioning after axillary lymph node dissection and predict late arm morbidity. To increase patients' quality of life it thus may serve as a valid assessment tool for screening, allowing early referral for treatment and monitoring.

Bock K, Duda VF, Hadji P, Ramaswamy A, Schulz-Wendtland R, Klose KJ, Wagner U. · Medizinisches Zentrum für Frauenheilkunde und Geburtshilfe, Philipps-Universität Marburg, Pilgrimstein 3, 35033 Marburg, Germany. · J Ultrasound Med. · Pubmed #16179617 No free full text.

Abstract: 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.

Sesterhenn AM, Albert US, Barth PJ, Wagner U, Werner JA. · Department of Otolaryngology, Head and Neck Surgery, Philipps University, Deutschhausstrasse 3, D-35037 Marburg, Germany. · Breast. · Pubmed #16061381 No free full text.

Abstract: Metastases to cervical lymph nodes do not exclusively derive from malignancies of the head and neck area. In the literature the region where distant metastases of breast carcinomas to the neck occur is exclusively named "supraclavicular". The system established by head and neck surgeons regarding neck node topography allows interdisciplinary management of patients with cervical lymph node metastases from breast cancer. Twelve patients suffering from breast cancer who presented with cervical masses have been examined. Most lymph node metastases were found in the posterior triangle of the neck and at the caudo-jugular level, but some metastases were even found in the upper jugular levels. The results presented show that neck node metastases of breast cancer are located superiorly to the supraclavicular region in more than 50% of the cases. According to the AJCC Staging System for Breast Cancer metastases located in the supraclavicular fossa are assessed as loco-regional metastases (N3c). Lymph node metastases situated above the supraclavicular region are not mentioned, but should be considered as distant metastases. This important question remains unanswered and deserves clarification in the current classification of the AJCC Staging System for Breast Cancer.

Albert US, Koller M, Lorenz W, Doherty J, Schulz KD, Wagner U, Kopp I. · Klinik für Gynäkologie, gynäkologische Endokrinologie und Onkologie, Klinikum der Philipps-Universität Marburg. · Z Arztl Fortbild Qualitatssich. · Pubmed #15487382 No free full text.

Abstract: Systematically developed, evidence- and consensus-based guidelines are important tools for improving health care services. The effectiveness of a guideline does not only relate to its methodological quality but also to the implementation strategy used. The following paper describes the systematic development of a strategy for implementing and evaluating the guideline "Early Detection of Breast Cancer in Germany" as part of a national project. A multi-faceted systematic implementation strategy has been developed addressing existing barriers and building on projects that have recently been introduced in Germany to improve the early detection and management of breast cancer. The aim is to induce behavioural changes in women as healthcare recipients and physicians as healthcare providers, both involved in the medical decision-making process within the scope of the guideline. Furthermore, it supports organisational changes to assure compliance with the guideline by means of quality assurance and quality management. To ensure evaluation of the implementation process a set of quality indicators have been identified for the baseline assessment of structures, provider performance and outcomes. Both the effectiveness of the implementation process and the effectiveness of the guideline itself will be measured by using the same set of indicators for reevaluation within a pre-defined time interval of 18 months. The quasi-experimental design of this uncontrolled before and after implementation study outlined in the present paper allows the assessment of clinically relevant changes using quality indicators that measure the effectiveness of the guideline on a national level.

Albert US, Koller M, Wagner U, Schulz KD. · Dept. of Gynecology, Gynecological Endocrinology and Oncology, Philipps-University Marburg, Pilgrimstein 3, 35037, Marburg, Germany. · Inflamm Res. · Pubmed #15338065 No free full text.

Abstract: BACKGROUND: The present analysis focuses on the long term psychological reactions to early stage breast cancer. Two hypotheses were formulated. The first hypothesis draws a direct link between tumour size/survival chances and Quality of life (QoL): The better the survival chances, the better QoL ('biological danger model'). The second hypothesis assumes that localized early breast cancer has excellent prognosis (> 90% five year survival rate), and that therefore QoL differences between various forms of early breast cancer should be minimal ('medico-pragmatic model'). PATIENTS AND METHODS: In a defined rural area with 252.000 inhabitants (small-area-analysis), a total of n = 389 patients with primary breast cancer were recruited. For the present analysis we selected a subgroup (n = 269) from the cohort by tumour size (pTis, pT1a,b, pT1c, and pT2). QoL scores for global quality of life, emotional functioning and future perspective were computed according to the EORTC manual and compared to age-matched norm data of the German population. RESULTS: A total of 690 QoL questionnaires were obtained from n = 269 patients with comparable completion rates within the four subgroups (pTis, pT1a,b, pT1c, and pT2).For all four groups and in all scores there were improvements over time. Generally, pTis always scored highest, pT2 always lowest, the other two groups in between.After one year pTis patients had higher mean scores in global quality of life than the norm. In contrast, pT1a,b were considerably lower than the norm and the difference between these two was 17.2 score points. It seems that the small difference (3.5%) in five year survival chances between pTis and T1 a,b tumours transforms into marked differences regarding quality of life, thus supporting a biological danger model of the survival/QoL relationship. CONCLUSIONS: Our results show that physicians have to realise although their early breast cancer patients have excellent survival chances, psychological distress is present. From a clinical perspective we would recommend that early stage breast cancer patients, and especially patients with occult, pT1a,b tumours be informed about their excellent prognosis. In addition, cognitive therapy might help patients stop worrying about their cancer.

Simon R, Atefy R, Wagner U, Forster T, Fijan A, Bruderer J, Wilber K, Mihatsch MJ, Gasser T, Sauter G. · Institute for Pathology and Urologic Clinics, University of Basel, Basel, Switzerland. · Int J Cancer. · Pubmed #14566826 No free full text.

Abstract: HER-2/NEU is one of the most frequently amplified oncogenes and a potential therapeutic target in bladder cancer. In breast cancer, the adjacent TOP2A gene, the molecular target for several anticancer drugs, is frequently coamplified together with HER-2. To study the amplification and expression of TOP2A and HER-2 and associations with tumor phenotype and clinical outcome in bladder cancer, a tissue microarray containing 2,317 bladder tumor samples was analyzed by FISH and immunohistochemistry. Overall amplification frequencies were 6.3% for HER-2 and 1.5% for TOP2A. Amplifications were most frequently seen in advanced-stage (pT2-4) tumors (HER-2 13.8%, TOP2A 3.4%). Of HER-2-amplified tumors, 56% also had alterations of TOP2A, including 14.7% coamplifications, 33.3% gains and 8% deletions. Only 17.6% of TOP2A amplifications occurred independently of HER-2 alterations. Both HER-2 and TOP2A amplifications were significantly associated with advanced tumor stage (HER-2 p < 0.0001, TOP2A p = 0.0218), high grade (p < 0.0001 for both) and protein overexpression (p < 0.0001 for both). TOP2A amplification and overexpression were linked to shortened survival in muscle-invasive tumors (p = 0.0042 and 0.0077, respectively). In summary, our data suggest that HER-2 amplifications are frequently linked to alterations of the TOP2A gene in bladder cancer. The anatomy of the 17q12-q21 amplicon may be important for response to therapies targeting HER-2 or TOP2A.

Andersen CL, Monni O, Wagner U, Kononen J, Bärlund M, Bucher C, Haas P, Nocito A, Bissig H, Sauter G, Kallioniemi A. · Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. · Am J Pathol. · Pubmed #12107091 links to  free full text

Abstract: The chromosomal region 17q23 has been shown to be commonly amplified in breast tumors, especially those with poor prognosis. In addition to breast cancer, studies by comparative genomic hybridization have implicated the involvement of 17q23 in other tumor types as well. Here we performed a large-scale survey on the distribution and frequency of the 17q23 copy number increases across different tumor types using fluorescence in situ hybridization on tissue microarrays containing 4788 specimens. A total of 4429 tumor samples representing 166 different tumor categories and 359 normal tissue samples from 40 different tissue categories were analyzed. Successful hybridizations were observed in 3520 of the 4788 specimens (74%). Increased 17q23 copy number was detected in 15% of the evaluable specimens with tumors originating from the lung, mammary gland, and soft tissue being most frequently affected. Interestingly, high-level amplification was detected only in 2% of the tumors and was generally restricted to mammary tumors. In addition, we observed an association between the frequency of increased 17q23 copy number and tumor progression in various tumor types. These results indicate that increased 17q23 copy number occurs frequently in several different tumor types suggesting that increased dosage of genes in this region might play a role in development and progression of many tumor types.

Cardiff RD, Wagner U, Hennighausen L. · Center for Comparative Medicine, University of California, Davis, USA. · Vet Pathol. · Pubmed #11467469 links to  free full text

This publication has no abstract.

Cardiff RD, Wagner U, Hennighausen L. · Department of Pathology and Center for Comparative Medicine, University of California, Davis 95616, USA. · J Mammary Gland Biol Neoplasia. · Pubmed #11149576 No free full text.

Abstract: This article introduces a CD-ROM containing whole-mount and histological images of normal growth and development of both the mouse mammary gland and the human breast. It also covers nonneoplastic lesions and neoplasias in both species including a catalog of lesions in genetically engineered mice. Instructions, with examples, on techniques such as whole-mount preparation, immunohistochemistry, in situ hybridization, and common histological stains are provided. The images are based on full-scale 1996 x 1640 pixel images at 300 pixels/ inch and are annotated. Every genetically engineered model has one or more accompanying citations. Tables are provided for orientation and organization. The CD includes zoom capabilities, a search engine, and a help mode.