Harald Sommer - Academia.edu (original) (raw)

Papers by Harald Sommer

Geburtshilfe und Frauenheilkunde, 2008

Gynäkologisch-geburtshilfliche Rundschau, 2004

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Zentralblatt Fur Gynakologie, 2006

: Pregnancy, leading to new life, on one hand, and life threatening malignancies an the other han... more : Pregnancy, leading to new life, on one hand, and life threatening malignancies an the other hand, are per se diametric subjects. Symptoms of malignancies are ignored more frequently during pregnancy by patients and physicians, often resulting in delayed diagnosis. Diagnosis and treatment of gynaecological malignancies, however, are increasingly important for four reasons: the peak incidence of several malignancies occurs during the reproductive age; late pregnancies present more often in an age group with increased risk for cancer, intensified care for pregnant women leads to more thorough diagnosis, and, curative treatment of malignancies gives women the potential chance for becoming pregnant. For these reasons, special features of the diagnosis and treatment of gynaecological malignancies will regularly part of routine patient care. This review article covers certain practice related features of gynaecological malignancies.

The Breast, 2003

It remains unclear, whether breast cancer pts. with more than 3 involved axillary lymph nodes ben... more It remains unclear, whether breast cancer pts. with more than 3 involved axillary lymph nodes benefit from adding taxanes to their adjuvant cytostatic therapy. Furthermore, the optimal timing of the taxane therapy, either simultaneously or sequential to anthracycline therapy, has to be clarified. Aim of this ongoing study is to compare toxicity and survival rates of pts. with either taxane or anthracycline based therapy. Open-label, multicenter, Phase Ill study, prospectivelly randomising pts. to adjuvant chemotherapy with 4 cycles of Epirubicin 90 mgIm2 and Cyclophosphamide 600 mg/m2 q3w, followed by 4 cycles ot Docetaxel 100 mg/m2 q3w (EC-Dot) or 6 cycles of Epirubicin 60 mg/m2 i.v. d 1+8, 5-Fluorouracil 500 mg/m2 i.v. d 1+8 and Cyclophosphamide 75 mgIm2 p.o. d I-14, q4w (FECIPO according to Levine). Pts. with positive hormone receptor status receive endocrine therapy, and all pts. are required to receive adjuvant radiotherapy. On 29/l l/O2 270 pts. were randomised. Primary tumor characteristics, such as tumor size (p = 0.48) axillary lymph node status (p = 0.39) and hormone receptor status (p = 0.64) were well balanced between both therapy arms. 22% of pts. presented with a tumor size I 2cm, 57% of pts. with a tumor size of 2 cm to 5 cm. The median number of involved lymph nodes was 8. 43% of tumors were poorly differentiated (G 3). Feasibility data of an interims analysis ot the first 500 cycles of chemotherapy will be presented at the meeting. In the adjunct scientific program, the predictive value of uPA/PAI-1 on the primary tumor and of the presence of disseminated tumor cells in the bone marrow at primary diagnosis as well as after completion of chemotherapy, is investigated. Supported by excellent patient recruitement, the ADEBAR Study will contribute further information on the role of taxanes in the adjuvant setting of high risk breast cancer patients. m Primary endpoint analysis of the GEPARDUO study: Comoarina dose-dense with seouential adriamyciii/docetaxel combination as preoperative chemotherapy (PCHT) in operable breast cancer (T2-3, NO-2, MO) .-. .

Cancer Chemotherapy and Pharmacology, 2009

Purpose EVective treatment options for patients with metastatic breast cancer (MBC) resistant/ref... more Purpose EVective treatment options for patients with metastatic breast cancer (MBC) resistant/refractory to anthracyclines and/or taxanes are limited. Intravenous and oral combination of vinorelbine (VRL) and capecitabine were shown to be feasible and eVective in Wrst-line MBC. In order to evaluate the activity of the combination of an all oral regimen in a more advanced setting, we investigated a regimen combining oral VRL and capecitabine in a phase II study as second-line chemotherapy of MBC patients previously treated with anthracyclines and taxanes. Patients and methods Forty patients (median age 52 years) with MBC received the combination of oral VRL 60 mg/m² on days 1, 8 and 15 plus capecitabine 1,000 mg/m² bid given from day 1 to day 14 in an open-label, international, multicentre, phase II study. Cycles were repeated every 3 weeks. The primary endpoint was response rate (RR) evaluated by an independent panel review. Secondary objectives included safety, duration of response, progressionfree survival, overall survival and quality of life. Results All the patients had received prior chemotherapy with anthracyclines and taxanes, 75% were refractory/resistant to anthracycline and/or taxane, 72.5% presented with visceral involvement and the last prior chemotherapy for 87.5% of the patients was for advanced disease setting. The median number of administered cycles per patient was 4 (range 1-31). Eight responses were documented and validated by an independent panel review, yielding RRs of 20% [95% CI: 9-35.6] in the intent-to-treat (treated) population and 23.5% [95% CI: 10.7-41.2] in the 34 evaluable patients. Median progression-free survival and median overall survival were 3.4 months [95% CI: 2.3-5.5] and 11.3 months [95% CI: 8.1-16.4], respectively. The principal toxicities were anaemia, neutropenia (rarely complicated; only one patient experienced febrile neutropenia), fatigue and gastrointestinal toxicities with very few grade 3-4 non-haematological toxicities. Conclusions In second-line treatment of MBC patients previously treated with anthracyclines and taxanes, oral VRL plus capecitabine is a safe regimen with an eYcacy comparable to the other available combination regimens used in this heavily and resistant/refractory (75% of patients) pre-treated patients' population. Moreover, this This study was supported by an unrestricted grant from

Geburtshilfe und Frauenheilkunde, 2013

Senologie - Zeitschrift für Mammadiagnostik und -therapie, 2008

Journal of Clinical Oncology, 2012

10540 Background: Recent reports showed a discrepancy in the Her2-status of metastases or minimal... more 10540 Background: Recent reports showed a discrepancy in the Her2-status of metastases or minimal residual disease in blood and bone marrow compared to the primary tumor in patients with breast cancer. The Her2-status of CTC was prospectively evaluated in the German multicenter SUCCESS B study. Methods: The SUCCESS B trial is a randomized Phase III study comparing FEC-Docetaxel (Doc) vs. FEC-Docetaxel-Gemcitabine (Doc-G) as well as Her2 targeted therapy with Trastuzumab as adjuvant treatment in patients with early, Her2 positive, node positive or high risk node negative primary breast cancer. As part of the translational research program, 23ml of peripheral blood were drawn before adjuvant chemotherapy. In 638 samples CTC and Her2-status were assessed using the CellSearch System (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for Her2 phenotyping. Cut...

Geburtshilfe und Frauenheilkunde, 2002

Beim Mammakarzinom etablierte sich in den letzten Jahrzehnten zunehmend die brusterhaltende Thera... more Beim Mammakarzinom etablierte sich in den letzten Jahrzehnten zunehmend die brusterhaltende Therapie. Da es jedoch gerade bei dieser Erkrankung häufig sowohl zu Spätrezidiven, als auch Spätkomplikationen kommen kann, ist es wichtig, in regelmäûigen Abständen diese Therapiemodalität durch Langzeitanalysen an groûen Patientenkollektiven zu reevaluieren. Methode: In der Universitätsklinik Berlin-Charlottenburg und der I. Frauenklinik der Ludwig-Maximilians-Universität München wurden zwischen 1963 und 2000 insgesamt 4799 an Brustkrebs erkrankte Frauen operativ behandelt. Hiervon konnten 1098 Patientinnen mit invasivem Mammakarzinom der Stadien pT 1 ± 2, N 0 ± 1, M 0 brusterhaltend therapiert werden. Die Behandlung bestand aus Tumorektomie mit axillärer Dissektion und anschlieûender Bestrahlung der Restbrust bis zu einer Dosis von 50 Gy. Im Rahmen einer Longitudinalstudie wurden die Basis-und Verlaufsdaten dieser Patientinnen kontinuierlich und zeitnah dokumentiert und bezüglich des Gesamt-und rezidivfreien Überlebens sowie der therapieassoziierten Komplikationen ausgewertet. Durch uni-und multivariate Analyse wurde die Bedeutung verschiedener Einflussfaktoren auf das Gesamtund das rezidivfreie Überleben geprüft.

Pollution of surface waters by runoff from sealed areas is coming more into focus. As shown by se... more Pollution of surface waters by runoff from sealed areas is coming more into focus. As shown by several national and international studies, this part of wastewater cannot be neglegted. There are different strategies to reduce emission from urban runoff. One is to reduce the pollution load to rivers and lakes by centralised retention, purification tanks and centralised constructed wetlands. An alternative strategy is source control. The presented solution in this paper concerns the thousands of inlets in urban areas draining highly polluted runoff from roads and highways. This solution consists of a cartridge that can be inserted into standard inlets. Within 2 filtration steps, a settling volume and a adsorptive filtration, the inflowing runoff is treated. The results of the quality measurements are: - a mixture of special filter sand with an adsorptive material is suitable for different inorganic and organic compounds. - a high retention for suspended solids was found - a significant...

Switching a city's stormwater management strategy from a "disposal mentality" towar... more Switching a city's stormwater management strategy from a "disposal mentality" towards a more sustainable, source control oriented approach is a difficult task. To convince decision makers, not only ecological but also financial arguments are necessary. One way to support the decision making process is to present the benefits of an alternative option in a so called decision matrix, a format which is well -known from product reviews in consumer magazines. The scope of this matrix is to compare different stormwater management options against relevant criteria like costs, impact on the environment, amenity, etc. In this paper the steps necessary to set up a decision matrix are described. In addition two tools supporting the approach are presented. With STORM; a hydrological model for simulating stormwater runoff and pollution load, the effects of different stormwater management measures- especially SUDS - on different indicators can be quantified. The COFAS-method is a too...

Molecular Medicine Reports, 2018

The primary cause of breast cancer-associated mortality is the formation of distant metastasis. D... more The primary cause of breast cancer-associated mortality is the formation of distant metastasis. During the metastatic process, single tumor cells dissolve from the primary tumor site and undergo various changes in cell adhesion and motility properties. The tumor cells invade the blood stream and travel to different sites of the body, where they may initiate outgrowth. These cells are referred to as circulating tumor cells (CTCs). The process of changing cellular properties is known as epithelial to mesenchymal transition (EMT). As a different set of genes is upregulated during EMT, such genes may serve as marker genes for the detection of CTCs based on reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Therefore, EMT-and breast cancer-related genes were selected as RT-qPCR markers. These genes were tested for performance in a model system of blood samples from healthy donors, to which a number of various breast cancer cell lines were added. The genes with optimal performance were subsequently used in RT-qPCR with 35 breast cancer patient samples. The genes which showed the highest and most consistent increase in gene expression with the increase in the number of cancer cell line cells added were CK19, Snail, FoxC2 and Twist. Following RT-qPCR for all patient samples, two subgroups were arranged: One group in which all genes were downregulated and the second group with at least one gene indicated an upregulation of gene expression. Comparisons were made between the tumour characteristics from these two groups. Results suggested that carcinomas of the first group exhibited a less aggressive tumor biology compared with those in the second group. The present study indicated a novel RT-qPCR based test for tumor malignancy.

Zentralblatt für Gynäkologie, 2005

Journal of Clinical Oncology, 2004

5139 Background: Topotecan (Hycamtin), a topoisomerase-I-inhibitor is established in the therapy ... more 5139 Background: Topotecan (Hycamtin), a topoisomerase-I-inhibitor is established in the therapy of relapsed OC. Ganem et al (ASCO 1998, abstr.1371) reported good tolerability and a remission rate of 22% for a topotecan/etoposide (T/E) combination in 80 heavily pretreated patients (pts). Gemcitabine has also demonstrated activity in resistant OC. In our recent published study (Ann Onc 2003) we describe a highly active combination of topotecan/gemcitabine (T/G) with a median TTP of 9.8 months for relapsed OC pts. Based on promising phase II results, a phase III study has been conducted to compare topotecan monotherapy (T) with T/E and T/G. The primary endpoint is median survival. Safety results from the planned interim analysis are reported for the first time. METHODS Pts with relapsed ovarian cancer after primary therapy have been stratified according to treatment-free interval of less or more than 12 months respectively. Arm A consisted of T 1.25mg/m2/d, d1-5; arm B of T 1.0mg/m2/d, d1-5 and E 50mg/d oral, d6-12; and arm C of T 0.5mg/m2/d, d1-5 and G 800mg/m2 d1 and 600mg/m2 d8. RESULTS In December 2003 435 pts were randomized. Safety data for 374 pts (mean age 60.5 years, ECOG 0-2, relapse <12 mo 219 pts and >12 mo 152 pts) with 143/142/89 pts in arm A/B/C respectively are available. According to study design pts were randomized to arms A or B. After recruiting 139 pts, arm C opened and randomization continued in the relation 1:1:2. Pts received a median of 6 cycles in arm A and B and 4 in arm C. Grade 4 events per pt are 0.21% (99% CI: 0.54-1.32) in arm A, 0.34% (99% CI: 0.17-0.5) in arm B and 0.29% (99% CI: 0.09-0.49)in arm C; p=.31. Main tox was leukopenia and thrombopenia. Leukopenia seems to be slightly higher in arm B but was below 1% of all events. Nonhematologic tox included nausea, emesis, diarrhea and alopecia were seldom and in the treatment arms similar. CONCLUSIONS The three treatment arms are safe and well tolerated. Recruitment is ongoing until the target of 133 evaluable pts has been achieved for each arm. We expect close of recruitment by ASCO 2004. No significant financial relationships to disclose.

Geburtshilfe und Frauenheilkunde, 2001

Dem Lokalrezidiv nach Mastektomie wird häufig eine schlechtere Prognose zugeschrieben, als dem Lo... more Dem Lokalrezidiv nach Mastektomie wird häufig eine schlechtere Prognose zugeschrieben, als dem Lokalrezidiv nach brusterhaltender Therapie bei Mammakarzinom. Es bleibt jedoch unklar, ob dies durch eine Ungleichverteilung der Prognosefaktoren zum Zeitpunkt der Primärtherapie oder durch eine unterschiedliche tumorbiologische Dynamik der Rezidivierung verursacht wird. Fragestellung: Lässt sich im Langzeitverlauf auch bei Patientinnen mit der primär guten Prognose eines pT1 ± 2N0 Mammakarzinoms ein Unterschied im Überleben nach dem Lokalrezidiv nach Mastektomie vs. BET nachweisen? Methode: Matched-Pair-Analyse von 62 nodalnegativen Patientinnen, die nach primärer R0-Resektion eines pT1 ± 2 Mammakarzinoms ein Lokalrezidiv ohne Anhalt für Fernmetastasierung erlitten. Die Paarbildung erfolgte nach gröûtmöglicher Übereinstimmung in Tumorgröûe, Tumorgrading und Alter. Durch uni-und multivariate Analyse wurde die Bedeutung verschiedener Einflussfaktoren auf das Überleben nach dem Rezidiv geprüft. Die mittlere Nachbeobachtungszeit betrug 7,5 Jahre. Ergebnisse: Die Patientenkollektive wiesen keine Unterschiede in Bezug auf die Prognosefaktoren primäre Tumorgröûe (p = 1,00) und histopathologisches Grading (p = 0,60) und in Bezug auf die Gröûe der Rezidivtumoren (p = 0,63) auf. Das Lokalrezidiv trat bei Patientinnen nach Mastektomie im Schnitt 8 Monate früher auf als bei Patientinnen nach BET (p = 0,35). Patientinnen in der Mastektomiegruppe wiesen ein geringeres Überleben nach dem Rezidiv auf (98 Monate), als Patientinnen in der BET-Gruppe (205 Monate). Dieser Unterschied erreicht jedoch kein statistisch signifikantes Niveau (p = 0,11). Sowohl in der univariaten wie in der multivariaten Analyse zeigte sich die Länge des rezidivfreien Intervalls als einziger unabhängiger prognostischer Einflussfaktor auf das Überleben nach dem Rezidiv (univariat: p = 0,015; multivariat: p = 0,0011), jedoch nicht der primäre Operationsmodus. Schlussfolgerung: Die schlechtere Überlebensprognose von Patientinnen (n = 62) mit einem Lokalrezidiv nach Mastektomie wegen eines nodalnegativen Mammakarzinoms scheint vor allem mit dem durchschnittlich kürzeren rezidivfreien Intervall dieser Patientinnen assoziiert zu sein.

Breast Cancer Research, 2005

There is compelling evidence from transgenic mouse studies and analysis of mutations in human car... more There is compelling evidence from transgenic mouse studies and analysis of mutations in human carcinomas indicating that the TGF-β signal transduction pathway is tumor suppressive. We have shown that overexpression of TGF-β1 in mammary epithelial cells suppresses the development of carcinomas and that expression of a dominant negative type II TGF-β receptor (DNIIR) in mammary epithelial cells under control of the MMTV promoter/enhancer increases the incidence of mammary carcinomas. Studies of human tumors have demonstrated inactivating mutations in human tumors of genes encoding proteins involved in TGF-β signal transduction, including DPC4/Smad4, Smad2, and the type II TGF-β receptor (TβRII). There is also evidence that TGF-β can enhance the progression of tumors. This hypothesis is being tested in genetically modified mice. To attain complete loss of TβRII, we have generated mice with loxP sites flanking exon 2 of Tgfbr2 and crossed them with mice expressing Cre recombinase under control of the MMTV promoter/enhancer to obtain Tgfbr2 mgKO mice. These mice show lobuloalveolar hyperplasia. Mice are being followed for mammary tumor development. Tgfbr2 mgKO mice that also express polyoma virus middle T antigen under control of the MMTV promoter (MMTV-PyVmT) develop mammary tumors with a significantly shorter latency than MMTV-PyVmT mice and show a marked increase in pulmonary metastases. Our data do not support the hypothesis that TGF-β signaling in mammary carcinoma cells is important for invasion and metastasis, at least in this model system. The importance of stromal-epithelial interactions in mammary gland development and tumorigenesis is well established. These interactions probably involve autocrine and paracrine action of multiple growth factors, including members of the TGF-β family, which are expressed in both stroma and epithelium. Again, to accomplish complete knockout of the type II TGF-β receptor gene in mammary stromal cells, FSP1-Cre and Tgfbr2 flox/flox mice were crossed to attain Tgfbr2 fspKO mice. The S.03 Genomic analysis of human breast cancer in families and populations

Deut Med Wochenschr, 2008