Von Minckwitz G.,German Breast Group |
Eidtmann H.,Universitats Frauenklinik |
Rezai M.,Luisenkrankenhaus |
Fasching P.A.,Friedrich - Alexander - University, Erlangen - Nuremberg |
And 19 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, has shown clinical efficacy in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We evaluated the efficacy, measured according to the rate of pathological complete response (absence of invasive and intraductal disease in the breast and the axillary lymph nodes), and the safety of adding bevacizumab to neoadjuvant chemotherapy in patients with early-stage breast cancer. METHODS: We randomly assigned 1948 patients with a median tumor size of 40 mm on palpation to receive neoadjuvant epirubicin and cyclophosphamide followed by docetaxel, with or without concomitant bevacizumab. Patients with untreated HER2-negative breast cancer were eligible if they had large tumors, hormone-receptor-negative disease, or hormone-receptor-positive disease with palpable nodes or positive findings on sentinel-node biopsy, and no increased cardiovascular or bleeding risk. RESULTS: Overall, the rates of pathological complete response were 14.9% with epirubicin and cyclophosphamide followed by docetaxel and 18.4% with epirubicin and cyclophosphamide followed by docetaxel plus bevacizumab (odds ratio with addition of bevacizumab, 1.29; 95% confidence interval, 1.02 to 1.65; P = 0.04); the corresponding rates of pathological complete response were 27.9% and 39.3% among 663 patients with triple-negative tumors (P = 0.003) and 7.8% and 7.7% among 1262 patients with hormone-receptor-positive tumors (P = 1.00). Breast-conserving surgery was possible in 66.6% of the patients in both groups. The addition of bevacizumab, as compared with neoadjuvant therapy alone, was associated with a higher incidence of grade 3 or 4 toxic effects (febrile neutropenia, mucositis, the hand-foot syndrome, infection, and hypertension) but with a similar incidence of surgical complications. CONCLUSIONS: The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome. (Funded by Sanofi-Aventis and Roche, Germany; ClinicalTrials.gov number, NCT00567554.) Copyright © 2012 Massachusetts Medical Society.
Simoes E.,Universitatsfrauenklinik Tubingen |
Brucker S.,Universitatsfrauenklinik Tubingen |
Beckmann M.W.,Universitatsklinikum |
Ortmann O.,University of Regensburg |
And 2 more authors.
Geburtshilfe und Frauenheilkunde | Year: 2013
With the development of a National Cancer Plan published in 2012, Germany has followed the recommendations of the WHO and the EU. The first area of action listed in Germanys National Cancer Plan is improving the early detection of cancer. Both citizens and medical specialists are encouraged to take responsibility themselves and contribute to the efforts being made to meet the challenge of cancer. Screening for cervical cancer has long been an integral part of the German Directive for the Early Detection of Cancer and now - following the recommendations given in the European Guideline - an organised screening approach shall be developed to maximise the benefits and minimise the risks through a partial reorganisation of existing structures. Before this can be rolled out nationwide, it will be necessary to check the feasibility and suitability of new contents and organisational structures. The Federal Joint Committee which is largely responsible for the process according to the draft law on the implementation of the National Cancer Plan has emphasised the importance of evidence-based medicine and of collaboration between the autonomous governing bodies within the healthcare system to obtain viable results. For medical specialists, the follow-on question is which areas will need more research in future. New process steps need to be developed and verified to see whether they offer evidence which will support defined approaches or whether such evidence needs to be newly compiled, e.g. by testing invitation procedures for screening in trial schemes. The experience gained during the implementation of the existing directive on early detection of cancer should be integrated into the new process. Research initiated by specialists could encourage the development of a new version of the Directive for the Early Detection of Cancer suitable for the Germanys healthcare system. © Georg Thieme Verlag KG Stuttgart · New York.
Hancke K.,Universitatsfrauenklinik |
Igl W.,Wilmar Igl Statistical Consulting |
Toth B.,University of Heidelberg |
Buhren A.,Praxis fur Psychosomatische Medizin und Psychotherapie |
And 2 more authors.
Archives of Gynecology and Obstetrics | Year: 2014
Purpose: Work-life balance is an upcoming issue for physicians. The working group "Family and Career" of the German Society for Gynecology and Obstetrics (DGGG) designed a survey to reflect the present work-life balance of female and male gynecologists in Germany. Methods: The 74-item, web-based survey "Profession-Family-Career" was sent to all members of the DGGG (n = 4,564). In total, there were 1,036 replies (23 %) from 75 % female gynecologists (n = 775) aged 38 ± 7 (mean ± standard deviation [SD]) years and 25 % male (n = 261) gynecologists aged 48 ± 11 years. Statistical analyses were performed using the mean and SD for descriptive analysis. Regression models were performed considering an effect of p ≤ 0.05 as statistically significant. Results: 47 % women and 46 % men reported satisfaction with their current work-life balance independent of gender (p gender = 0.15). 70 % women and 75 % men answered that work life and private life were equally important to them (p gender = 0.12). While 39 % women versus 11 % men worked part-time (p gender < 0.0001), men reported more overtime work than women (p gender < 0.0001). 75 % physicians were not satisfied with their salary independent of gender (p gender = 0.057). Work life affected private life of men and women in a similar way (all p gender > 0.05). At least 37 % women and men neglected both their partner and their children very often due to their work. Conclusions: Female physicians often described their work situation similar to male physicians, although important differences regarding total work time, overtime work and appreciation by supervisors were reported. Work life affected private life of women and men in a similar way. © 2013 Springer-Verlag Berlin Heidelberg.
Hacke K.,German Cancer Research Center |
Hacke K.,University of California at Los Angeles |
Rincon-Orozco B.,German Cancer Research Center |
Buchwalter G.,Institute Of Genetique Et Of Biologie Moleculaire Et Cellulaire |
And 5 more authors.
Molecular Cancer | Year: 2010
Background: Our previous studies showed that the expression of the monocyte-chemoattractant protein (MCP)-1, a chemokine, which triggers the infiltration and activation of cells of the monocyte-macrophage lineage, is abrogated in human papillomavirus (HPV)-positive premalignant and malignant cells. In silico analysis of the MCP-1 upstream region proposed a putative p53 binding side about 2.5 kb upstream of the transcriptional start. The aim of this study is to monitor a physiological role of p53 in this process.Results: The proposed p53 binding side could be confirmed in vitro by electrophoretic-mobility-shift assays and in vivo by chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-α can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-α treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-α addition, directly confirming a crosstalk between p53 and MCP-1.Conclusion: These data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment. © 2010 Hacke et al; licensee BioMed Central Ltd.
De Gregorio N.,Universitatsfrauenklinik
Gynakologe | Year: 2011
We report the case of a 27-year-old nulliparous with elevated β-HCG levels after two curettages following an incomplete abortion. A high risk choriocarcinoma was diagnosed. After 13 cycles of methotrexate the β-HCG level was under the detection limit, however, transvaginal sonography showed a highly vascularized uterine tumor. Operative hysteroscopy was performed but the pathological findings showed only amorphous necrotic tissue without viable cells. © 2011 Springer-Verlag.
Kehl S.,University of Mannheim |
Weigel M.,Leopoldina Hospital |
Muller D.,University of Mannheim |
Gentili M.,University of Mannheim |
And 3 more authors.
Archives of Gynecology and Obstetrics | Year: 2011
Purpose: Serodiscordant couples with a human immunodeficiency virus type 1 (HIV-1)-infected man request assisted reproductive technology (ART) in order to achieve safe conception. Most of these men are on highly active antiretroviral therapy (HAART). HIV-1 infection and the antiretroviral drugs are blamed for semen alterations. The aim of our study was to investigate the semen parameters in HIV-1-infected patients with and without HAART and to compare their sperm characteristics with those of healthy men. Materials and methods: A prospective study of 226 men attended the university fertility center of Mannheim between May 1996 and July 2003. The patients were divided into three groups: HIV-infected men taking antiretroviral therapy, HIV-infected patients who did not take antiretroviral therapy until now and a control group with 93 men consulting our fertility center together with their wives because of tubal sterility. Semen samples were examined with regard to ejaculate volume, sperm concentration, motility, and morphology. Results: The study showed significant differences between the ejaculate of HIV-infected and non-infected men. The HIV-infected men as a whole group and the subgroup of men with HAART had a lower ejaculate volume, less slow progressive and more abnormally shaped spermatozoa compared with the control group. The HIV-infected men without an antiretroviral therapy had a significant lower ejaculate volume compared with the control group; the other parameters were not altered significantly. Differences between the subgroups with and without HAART were not significant. Conclusion: The spermiogram in HIV-1-infected men in comparison to a control group of healthy men is negatively altered. Especially in men with HAART, ejaculate volume as well as sperm morphology and motility changed significantly. © 2011 Springer-Verlag.
Maternal endothelial function in the course of pregnancy and postpartum - Ultrasound-based longitudinal assessment using flow-mediated dilatation (FMD) [Maternale Endothelfunktion in Schwangerschaft und Wochenbett - ultraschallgestützte longitudinale Erfassung mittels Flow Mediated Dilatation (FMD)]
Seeliger C.,Universitatsfrauenklinik |
Brueckmann A.,Universitatsfrauenklinik |
Ultraschall in der Medizin | Year: 2012
Purpose: NO-triggered vasodilatation decreases peripheral vascular resistance in pregnancy. Using a noninvasive ultrasound technique, flow-mediated vasodilatation can be quantified. We used this technique to detect changes in endothelial function during pregnancy and postpartum. Materials and Methods: In a prospective longitudinal study 16 healthy pregnant women were assessed for flow-mediated dilatation of the brachial artery during pregnancy (first trimester T 1 < 14th gestational week, second trimester T 2 14th - 27th gestational week, third trimester T 3 28th gestational week) and postpartum (> 6 weeks postpartum). As a control group, flow-mediated dilatation was determined in 19 healthy non-pregnant women. Results: Flow-mediated dilatation (%) increased significantly in normal human pregnancy from the first trimester (T1 8.0 ± 5.58 vs. T 2 15.2 ± 5.19, p < 0.003) to the second trimester and reached its maximum in mid-trimester. Towards the end of pregnancy, flow-mediated dilatation decreased significantly (T2 vs. T 3 9.15 ± 3.61, p < 0.004). Mean values of flow-mediated dilatation are significantly higher during the second and third trimester of pregnancy compared to non-pregnant controls (T2 vs. NP 6.17 ± 4.39, p < 0.001; T 3 vs. NP, p < 0.047). Postpartum flow-mediated dilatation decreased to values of early pregnancy. Conclusion: During pregnancy maternal endothelial function shows an increase in flow-mediated dilatation and then reverts postpartum. Using ultrasound-based measurement of flow-mediated dilatation, these physiological changes in pregnancy can be reliably detected. © Georg Thieme Verlag KG Stuttgart · New York.
Chirurg | Year: 2010
The established gynecological cancer operations are based on functional anatomy derived from the mature organism and on a model of radial progressive tumor permeation. Surgical treatment aims to resect the tumor with a metrically defined radial margin of tissue microscopically free of neoplastic or dysplastic disease. However, despite adequate surgical performance local tumor relapses still occur. In the presence of histopathological risk factors adjuvant radiation is therefore recommended which increases treatment-related morbidity. The Leipzig School of Radical Pelvic Surgery has developed new gynecological cancer operations from a different perspective on anatomy and local tumor spread. Tissue mapping is deduced by following the organism's development from the stage of tissue deposition to maturity (ontogenetic anatomy) to define permissive compartments for cancer permeation. The variants of mesometrial resection (TMMR, PMMR) and vulva field resection (VFR) achieve very high (>95%) local control rates in stages I and II cancer of the lower and middle female genital tract without adjuvant radiation. Laterally extended endopelvic resection (LEER) provides sustained tumor control even in locally advanced and recurrent disease as well as cancer of the distal vagina. © 2010 Springer-Verlag.
Gynakologische Praxis | Year: 2012
The female sexual function is becoming more and more important in the urogynecological office. In the past years good anatomical outcome was the main intention of urogynecological surgery. Nowadays we have to consider that even in the group of women over 60 we find more than 54% regularly sexually active. Incontinence and pelvic organ prolapse impair libido and orgasm. Because of shame patients will not talk easily to their doctors about problems in their sexual life. Systematical asking about their sex life is a must in the urogynecological interview. Validated questionnaires can help. Restoring body image and treatment of dyspareunia as well as incontinence during intercourse could improve sexual life after incontinence and prolapse surgery. Indication and choice of type of surgery has to be adapted to the individual demands. Vaginal mesh implantation or transobturator slings have been shown to have significant higher rates of de novo dyspareunia. Excessive myorrhaphia should be avoided. An individualized treatment concept is the current way of medical care in all decades of female life.
Harbeck N.,Universitatsfrauenklinik |
Sotlar K.,Ludwig Maximilians University of Munich |
Wuerstlein R.,Ludwig Maximilians University of Munich |
Doisneau-Sixou S.,Ludwig Maximilians University of Munich |
Doisneau-Sixou S.,University Paul Sabatier
Cancer Treatment Reviews | Year: 2014
In early breast cancer (eBC), established clinicopathological factors are not sufficient for clinical decision making particularly regarding adjuvant chemotherapy since substantial over- or undertreatment may occur. Thus, novel protein- and molecular markers have been put forward as decision aids. Since these potential prognosis and/or predictive tests differ substantially regarding their methodology, analytical and clinical validation, this review attempts to summarize the essential facts for clinicians. This review focuses on those markers which are the most advanced so far in their development towards routine clinical application, i.e. two protein markers (i.e. uPA/PAI-1 and IHC4) and six molecular multigene tests (i.e. Mammaprint®, Oncotype DX®, PAM50, Endopredict®, the 97-gene genomic grade, and 76 gene Rotterdam signatures). Next to methodological aspects, we summarized the clinical evidences, in particular the main prospective clinical trials which have already been fully recruited (i.e. MINDACT, TAILORx, WSG PLAN B) or are still ongoing (i.e. RxPONDER/SWOG S1007, WSG-ADAPT). Last but not least, this review points out the key elements for clinicians to select one test among the wide panel of proposed assays, for a specific population of patients in term of level of evidence, analytical and clinical validity as well as cost effectiveness. © 2013 Elsevier Ltd.