Sherko Kümmel

Publications (34)105.82 Total impact

• Article: Neoadjuvant chemotherapy with paclitaxel and everolimus in breast cancer patients with non-responsive tumours to epirubicin/cyclophosphamide (EC)±bevacizumab - Results of the randomised GeparQuinto study (GBG 44).

  Jens Huober, Peter A Fasching, Claus Hanusch, Mahdi Rezai, Holger Eidtmann, Kornelia Kittel, Jörn Hilfrich, Kathrin Schwedler, Jens-Uwe Blohmer, Hans Tesch, [......], Sherko Kümmel, Christine Mau, Christian Jackisch, Fariba Khandan, Serban Dan Costa, Petra Krabisch, Sibylle Loibl, Valentina Nekljudova, Michael Untch, Gunter von Minckwitz
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  ABSTRACT: BACKGROUND: We tested the oral mammalian target of rapamycin (mTOR) inhibitor everolimus in addition to paclitaxel in patients with HER2-negative tumours not responding to initial neoadjuvant cytotoxic and anti-angiogenic treatment. METHODS: Patients with primary HER2-negative tumours received four neoadjuvant cycles of epirubicin/cyclophosphamide (EC) with or without bevacizumab. Patients without clinical response were randomised to receive weekly paclitaxel (80mg/m(2)) with or without everolimus (5mg p.o. daily, after a step-wise dose-escalation starting from 2.5mg bid) for 12weeks before surgery. To detect an increase in pathological complete response (pCR; ypT0 ypN0) from 5% to 12.1% (odds ratio 2.62) 566 patients had to be recruited. The trial was stopped prematurely due to completion of accrual in the main study. FINDINGS: Of 1948 patients initially starting neoadjuvant treatment 403 were randomised. A total of 18 (4.6%) patients, 7 (3.6%) treated with paclitaxel and everolimus and 11 (5.6%) treated with paclitaxel alone had a pCR (odds ratio 0.36 (OR) (95% confidence interval (CI), 0.24-1.6) p=0.34). Overall response rate in breast and lymph nodes at surgery was 52.2% after paclitaxel plus everolimus and 61.7% after paclitaxel alone (p=0.063). Breast conserving treatment was performed in 54.4% of patients with the combination treatment and 61.9% with paclitaxel alone (p=0.20). Mucosal inflammation, thrombocytopenia, neutropenia, infection, and skin rash were more frequent when everolimus was added to paclitaxel. INTERPRETATION: Neoadjuvant therapy with everolimus and paclitaxel for patients with HER2-negative disease unresponsive to EC with or without bevacizumab did not improve the pCR rate. Long-term outcome is awaited. FUNDING: Novartis, Roche, and Sanofi-Aventis.
  European journal of cancer (Oxford, England: 1990) 03/2013; · 4.12 Impact Factor
• Article: Influence of calcitriol on prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cell lines.

  Marc Thill, Tim Cordes, Friederike Hoellen, Steffi Becker, Christine Dittmer, Sherko Kümmel, Darius Salehin, Michael Friedrich, Klaus Diedrich, Frank Köster
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  ABSTRACT: Cyclooxygenase-2 (COX-2) is a potential molecular prognostic factor for breast cancer, and calcitriol [1,25(OH)(2)D(3)], the biologically active form of vitamin D, is a promising target in breast cancer therapy. The influence of calcitriol on the proliferation and the effects of calcitriol on the expression of prostaglandin- and vitamin D-metabolising enzymes were examined in benign and malignant breast cells. Calcitriol inhibited the proliferation of MCF-10F and MCF-7 cells but not of invasive MDA-MB-231 cells and reduced the expression of COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the benign breast cell line MCF-10F. Furthermore, dysregulation in vitamin D-metabolising proteins was detected, especially in MDA-MB-231 cells. These results suggest dysregulation of vitamin D metabolism and a lack of a possible influence of calcitriol on the metabolism of prostaglandins in the malignant breast cell lines.
  Anticancer research 01/2012; 32(1):359-65. · 1.73 Impact Factor
• Article: Expression of prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cells.

  Marc Thill, Friederike Hoellen, Steffi Becker, Christine Dittmer, Dorothea Fischer, Sherko Kümmel, Darius Salehin, Michael Friedrich, Frank Köster, Klaus Diedrich, Tim Cordes
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  ABSTRACT: Cyclooxygenase-2 (COX-2) plays a crucial role in prognosis of malignancy and has been associated with carcinogenesis, particularly neoangiogenesis and tumor progression. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumour suppressor in cancer. The antiproliferative effects of calcitriol [1,25(OH)(2)D(3)] mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. The expression of prostaglandin (PG)-metabolizing enzymes, vitamin D-metabolising enzymes and VDR were determined in benign and malignant breast cell lines using western blot analysis. We detected an inverse correlation between the two types of metabolism, a reduced VDR expression in the malignant breast cell lines, and therefore an insufficient induction of 24-hydroxylase in the malignant cells. We suggest the possibility of dysregulation of vitamin D-metabolizing enzymes in malignant breast cell lines.
  Anticancer research 01/2012; 32(1):367-72. · 1.73 Impact Factor
• Article: Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases in breast cancer.

  Steffen Hahn, Till Heusner, Sherko Kümmel, Angelika Köninger, James Nagarajah, Stefan Müller, Christian Boy, Michael Forsting, Andreas Bockisch, Gerald Antoch, Alexander Stahl
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  ABSTRACT: Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy. To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients. Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients. A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases. On a lesion-basis whole-body FDG-PET/CT is more sensitive and equally specific for the detection of bone metastases compared with bone scintigraphy.
  Acta Radiologica 11/2011; 52(9):1009-14. · 1.37 Impact Factor
• Article: Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study.

  Jens-Uwe Blohmer, Stefan Paepke, Jalid Sehouli, Dirk Boehmer, Martin Kolben, Florian Würschmidt, Karl U Petry, Rainer Kimmig, Dirk Elling, Christoph Thomssen, Gunter von Minckwitz, Volker Möbus, Axel Hinke, Sherko Kümmel, Volker Budach, Werner Lichtenegger, Peter Schmid
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  ABSTRACT: This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy. Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events. The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups. This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS.
  Journal of Clinical Oncology 08/2011; 29(28):3791-7. · 18.37 Impact Factor
• Article: First evaluation of the diagnostic accuracy of an automated 3D ultrasound system in a breast screening setting.

  Frank Stöblen, Solveig Landt, Ruth Stelkens-Gebhardt, Jalid Sehouli, Mahdi Rezai, Sherko Kümmel
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  ABSTRACT: Automated ultrasound examination of suspicious findings can reduce the physician's workload in screening mammography. The present study examines the diagnostic accuracy of this method in comparison to mammography as the reference standard for the first time. A total of 304 patients underwent automated 3D ultrasound examination after screening mammography. Mammograms and ultrasound images were assessed by independent examiners, and sensitivity, specificity and the degree of agreement between both methods were calculated. The degree of agreement was moderate (Cohen's κ=0.130 for all and 0.153 for positive/negative ratings), mainly owing to a high percentage of false-positive ultrasound results. However, the results of sonographical re-examination of suspicious mammograms were favorable. The only two undetected proven malignant lesions were microcalcified, and in three more cases with disagreement, the ultrasound diagnosis was correct. Automated 3D ultrasound imaging appears to be on a par with hand-held ultrasound in terms of diagnostic quality.
  Anticancer research 08/2011; 31(8):2569-74. · 1.73 Impact Factor
• Article: High-frequency breast ultrasound for the detection of microcalcifications and associated masses in BI-RADS 4a patients.

  Frank Stöblen, Solveig Landt, Rami Ishaq, Ruth Stelkens-Gebhardt, Mahdi Rezai, Per Skaane, Jens-Uwe Blohmer, Jalid Sehouli, Sherko Kümmel
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  ABSTRACT: To retrospectively evaluate the diagnostic value of high-frequency ultrasound for the detection of microcalcifications screening in BI-RADS 4a patients. A total of 52 women (mean age 60.5±6.5 years) classified as BI-RADS 4a with microcalcifications, but without associated masses after X-ray mammography (XRM) underwent ultrasound (US) examination (B-mode, ApliPure™ , and MicroPure™ imaging). The results were assessed by two independent investigators and analyzed in relation to the B-classification. Written informed consent was obtained before enrolment. The rate of US microcalcification detection was 98.1% (B-mode), 100% (ApliPure™) and 25% (MicroPure™), respectively. The microcalcification extent was significantly underestimated with all US modalities in comparison with XRM, but the difference was lower for ApliPure™ as compared to B-mode. ApliPure™ was also superior in terms of puncture feasibility, facilitating US-guided biopsy in 67.3% as compared to 48.1% (B-mode) and 15.4% (MicroPure™). In BI-RADS 4a patients, both high-frequency B-mode US and ApliPure™ imaging are highly sensitive for the detection of microcalcifications, whereas MicroPure™ ultrasound imaging is unsuitable. ApliPure™ imaging allowed US guided biopsy for 67.3% of lesions, providing a convenient and economical alternative to stereotactically guided biopsy.
  Anticancer research 08/2011; 31(8):2575-81. · 1.73 Impact Factor
• Article: Prognostic significance of angiogenic factors in uterine cervical cancer.

  Solveig Landt, Michael Wehling, Harald Heidecke, Sophia Jeschke, Susanne Korlach, Frank Stöblen, Peter Schmid, Jens-Uwe Blohmer, Werner Lichtenegger, Jalid Sehouli, Sherko Kümmel
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  ABSTRACT: Angiogenesis is pivotal in tumour development and progress, and targeted tumour therapies, such as bevacizumab, have shown promising results. However, in unselected patient populations, the treatment with angiogenesis-targeted combination regimens is marred by a variable response, non-negligible toxicity and questionable economy. The present study summarizes research to identify individual circulating angiogenic factors as markers for disease severity and possibly treatment response. A total of 125 patients with cervical cancer from the ongoing cervical cancer monitoring database of the University Hospital Charité, Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age, HER2, HPV, smoking and menopausal status, and serum concentrations of vascular endothelial growth factor (VEGF), VEGF-D, VEGF-C, endoglin, endostatin, angiogenin, basic fibroblast growth factor (FGFb), vascular endothelial growth factor receptor (VEGF-R1), VEGF-R2, soluble inter-cellular adhesion molecule 1 (sICAM 1), soluble vascular adhesion molecule 1 (sVCAM 1), insulin-like growth factor 1 (IFG-1) and insulin like growth factor binding protein 3 (IGF-BP3). There was a clear association of angiogenic factor concentrations with stage of disease. Angiogenin showed an independent discrimination for cervical intraepithelial neoplasia (CIN) and invasive stages, and endoglin did so for invasive stages vs. recurrent disease. However, none of the potential markers under investigation was anywhere near selective enough to allow for a clinically meaningful prediction of prognosis or response. The association of circulating angiogenic factors with disease progression in cervical cancer is confirmed, but its utility for prognosis prediction and patient stratification for targeted therapies is doubtful.
  Anticancer research 08/2011; 31(8):2589-95. · 1.73 Impact Factor
• Article: In vitro vascular tube formation testing as a tool for treatment individualisation in patients with cervical cancer.

  Solveig Landt, Harald Heidecke, Susanne Korlach, Cora Reuter, Ilka Schwidde, Jana Barinoff, Marc Thill, Jalid Sehouli, Sherko Kümmel
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  ABSTRACT: Targeted tumour therapies are promising, but their results in unselected patient populations are modest and tumour growth and metastasis may be promoted rather than suppressed in some cases. The present study investigates the suitability of vascular in vitro tube formation as a tool for the identification of cervical neoplasms that will respond to bevacizumab therapy. Fifteen patients with recurrent cervical cancer selected from the ongoing cervical cancer monitoring database of the Charité University Hospital Berlin, Germany, were included. Information obtained from the database included tumour stage, malignancy grade, presence of nodal metastases, lymph vessel invasion, patient age and menopausal status and serum concentrations of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and vascular endothelial growth factor receptor 1 (VEGF-R1). Vascular tube formation was assessed with cultured human umbilical vein epithelial cells. Five patients showed a positive, 5 an inverse and 5 no in vitro response to bevacizumab. Tube length showed a marked and significant dependency on bevacizumab response. Besides tube length, VEGF-R1 concentration was the only variable with some correlation to bevacizumab response, with high levels especially for inverse responders. The identification of patients with a likely benefit from targeted therapies is crucial. Tube formation shows substantial potential, but its utility needs to be confirmed in studies on the clinical rather than in vitro response to bevacizumab.
  Anticancer research 08/2011; 31(8):2609-15. · 1.73 Impact Factor
• Article: The utility of an in vitro angiogenesis score for prognosis assessment in patients with cervical cancer.

  Solveig Landt, Harald Heidecke, Cora Reuter, Susanne Korlach, Jens-Uwe Blohmer, Werner Lichtenegger, Till Heusner, Frank Stöblen, Marc Thill, Jana Barinoff, Jalid Sehouli, Sherko Kümmel
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  ABSTRACT: Angiogenesis plays a key role in tumour growth and metastasis. Expression of angiogenic factors has been suggested as a marker for tumour malignity, and may help to assess a patient's individual prognosis. The present study examines the relationship between angiogenic factor expression, an angiogenesis-based histoscore and clinical tumour criteria. A total of 81 patients with cervical cancer who underwent follow-up examinations between October 2002, and June 2005, were enrolled, and serum samples were examined for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), endostatin and VEGF-Receptor1 by means of an ELISA. Based on an endothelial-cell proliferation assay, an angiogenesis score was calculated. Higher endostatin and VEGF expressions indicated advanced disease, and VEGF allowed for a reliable distinction between patients with non-invasive and these with recurrent disease. There were some plausible correlations between the angiogenesis score and clinical criteria and individual angiogenic factors, but the score's discriminating power appears to be limited. The utility of angiogenesis factor testing notwithstanding, the value of an angiogenesis score for the identification of patients with a worse prognosis, and thus a resulting benefit from more aggressive treatment, is arguable.
  Anticancer research 08/2011; 31(8):2645-9. · 1.73 Impact Factor
• Article: Prognostic significance of the angiogenic factors angiogenin, endoglin and endostatin in cervical cancer.

  Solveig Landt, Konstanze Mordelt, Ilka Schwidde, Jana Barinoff, Susanne Korlach, Frank Stöblen, Werner Lichtenegger, Jalid Sehouli, Sherko Kümmel
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  ABSTRACT: Background/Aim: Angiogenesis plays a key role in tumour growth and metastasis. Expression of angiogenic factors has been suggested as a marker for tumour malignity, and it may help to identify those patients with a poorer prognosis, aiding patient stratification for more aggressive and/or angiogenesis-targeted therapy. The present study examines the relationship between concentration of circulating angiogenic factors and clinical tumour criteria as well as patient survival. A total of 125 patients with cervical cancer who underwent follow-up examinations between October 2002 and June 2005 were enrolled, and serum samples were examined for angiogenin, endoglin and endostatin by means of an ELISA. Concentrations were statistically correlated with clinical and outcome parameters. Concentrations of all examined angiogenic factors were on average within the manufacturer-provided normal range. Both angiogenin and endostatin increased from non-invasive tumours through invasive lesions to recurrent disease, and endoglin showed an equally steady inverse trend; differences between non-invasive, invasive and recurrent stages of the disease were statistically significant. However it was not possible to determine a sufficiently selective cut-off point for either factor by receiver operating characteristic analysis, and there was no significant correlation with survival. Angiogenic factors angiogenin, endoglin and endostatin show a definite relationship with disease stage in uterine cervical cancer, but are presently not suitable for use in risk stratification.
  Anticancer research 08/2011; 31(8):2651-5. · 1.73 Impact Factor
• Article: Influence of a dose-dense adjuvant chemotherapy on sVCAM-1/sICAM-1 serum levels in breast cancer patients with 1-3 positive lymph nodes.

  Holm Eggeman, Frank Stöblen, Marc Thill, Susanne Korlach, Peter Schmid, Diana Lüftner, Dirk Elling, Florin-Andrei Taran, Sherko Kümmel, Solveig Landt
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  ABSTRACT: The aim of the present study was to investigate the effects of conventional and dose-dense chemotherapy on serum levels of soluble adhesion molecules sICAM-1 and sVCAM-1 in node-positive patients with breast cancer. sICAM-1 and sVCAM-1 were measured in the blood serum of 147 patients with breast cancer and with 1 to 3 affected lymph nodes prior to and after conventional or dose-dense chemotherapy within a randomized phase III study (NOGGO trial). The increase in sICAM-1 (p<0.0001) and sVCAM-1 (p<0.001) levels after chemotherapy was statistically significant within the entire sample and the dose-dense study arm. sVCAM-1 levels were not altered by conventional chemotherapy, but were markedly and significantly increased after the dose-dense regimen. Higher sICAM-1 concentrations were found in postmenopausal patients, and the difference was significant before, but not after treatment. There was no significant correlation with other prognostic criteria. Both sVCAM-1 and sICAM-1 levels changed significantly after adjuvant chemotherapy, the effect being more marked under the dose-dense regimen. The possible prognostic relevance of adhesion molecule concentration and the effect of different modes of chemotherapy remains to be determined.
  Anticancer research 08/2011; 31(8):2617-22. · 1.73 Impact Factor
• Source

  Available from: peerproject.eu

  Article: Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials.

  Gunter von Minckwitz, Michael Untch, Eveline Nüesch, Sibylle Loibl, Manfred Kaufmann, Sherko Kümmel, Peter A Fasching, Wolfgang Eiermann, Jens-Uwe Blohmer, Serban Dan Costa, [......], Bernd Gerber, Andreas du Bois, Jens Huober, Claus Hanusch, Gottfried Konecny, Werner Fett, Elmar Stickeler, Nadia Harbeck, Volkmar Müller, Peter Jüni
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  ABSTRACT: Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.
  Breast Cancer Research and Treatment 11/2010; 125(1):145-56. · 4.43 Impact Factor
• Source

  Available from: PubMed Central

  Article: Imaging in patients with breast implants-results of the First International Breast (Implant) Conference 2009.

  Frank Stöblen, Mahdi Rezai, Sherko Kümmel
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  ABSTRACT: BACKGROUND: The First International Breast (Implant) Conference was held by the EAoS® (European Academy of Senology) in cooperation with the German Society of Senology during its 29th annual meeting in Düsseldorf, Germany, on 13 June 2009. METHODS: It was performed as a whole-day interactive workshop in which the standards of implant surgery within reconstructive and aesthetic breast surgery were discussed and defined by telecommunication dialogue voting. RESULTS: This article describes the conference results concerning pre- and post-procedural imaging in patients with breast implants. Both before and after augmentation, imaging is mandatory and provides essential information concerning tissue and implant integrity. Whereas mammography is the first-line method before surgery, ultrasound is the mainstay of post-procedural imaging. Cancer screening in augmented breasts generally follows the same guidelines as for non-augmented breasts. CONCLUSION: Whereas agreement about the indications for mammographical and sonographical evaluations is largely unanimous, there was substantial disagreement as far as the application of magnetic resonance imaging is concerned. There is an obvious demand for an evidence-based evaluation of this modality and the implementation of appropriate guidelines.
  Insights into imaging. 05/2010; 1(2):93-97.
• Article: [Screening for distress in women with breast cancer diagnosed for the first time: employment of HADS-D and PO-Bado].

  Yesim Erim, Mingo Beckmann, Gabriele Gerlach, Sherko Kümmel, Carsten Oberhoff, Wolfgang Senf, Rainer Kimmig
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  ABSTRACT: In the context of an intensification of efforts to ensure sufficient psychooncological care for breast-cancer patients, the discussion concerning valid psychometric screening instruments gains a special relevance. The discriminant and diagnostic validity of HADS-D and PO-Bado were investigated in a sample of 123 women with breast cancer diagnosed for the first time. An ROC analysis revealed a cut-off score of greater than 9 for the subscale anxiety (sensitivity: 50%; specificity: 90%) for the use of HADS-D among breast cancer patients, whereas the recommended cut-off value was greater than 7 (sensitivity: 56%; specificity: 80%) for the subscale depression. Based on the anxiety and depression scores measured by HADS-D, 74% of the clinical cases could be classified correctly. Scores for physical and mental distress measured with PO-Bado were significantly lower in the investigated sample than in the control sample. HADS-D has only a moderate sensitivity for the group at hand. PO-Bado is a comprehensive basic documentation for specific psychooncological distress, though without cut-off values it is not useful as a screening instrument.
  Zeitschrift fur Psychosomatische Medizin und Psychotherapie 01/2009; 55(3):248-62. · 1.30 Impact Factor
• Chapter: Relevance of Dose-Intensity for Adjuvant Treatment of Breast Cancer

  Sherko Kümmel, Mahdi Rezai, Rainer Kimmig, Peter Schmid
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  ABSTRACT: Despite all progress in the management of primary breast cancer in general and in perioperative systemic treatment in particular, many patients still relapse and eventually die as a consequence of their disease (EBCTCG, 2005) Thus, different approaches have been made to the improvement of preoperative or adjuvant polychemotherapy, including the addition of novel drugs such as taxanes or targeted agents or the establishment of dose-intensive or dose-dense regimens. This chapter outlines the theoretical framework for dose-dense chemotherapy, and reviews recent clinical trials that address this concept to adjuvant breast cancer treatment.
  11/2008: pages 351-360;
• Article: [Hormone replacement therapy in patients after breast cancer].

  Angela Köninger, Sherko Kümmel, Rainer Kimmig
  MMW Fortschritte der Medizin 11/2008; 150(43):32-4.
• Article: Neoadjuvant vinorelbine-capecitabine versus docetaxel-doxorubicin-cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial.

  Gunter von Minckwitz, Sherko Kümmel, Petra Vogel, Claus Hanusch, Holger Eidtmann, Jörn Hilfrich, Bernd Gerber, Jens Huober, Serban Dan Costa, Christian Jackisch, Sibylle Loibl, Keyur Mehta, Manfred Kaufmann
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  ABSTRACT: Among breast cancer patients, nonresponse to initial neoadjuvant chemotherapy is associated with unfavorable outcome. We compared the response of nonresponding patients who continued the same treatment with that of patients who switched to a well-tolerated non-cross-resistant regimen. Previously untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2), doxorubicin at 50 mg/m(2), and cyclophosphamide at 500 mg/m(2) per day (TAC). Patients whose tumors did not decrease in size by at least 50% were randomly assigned to four additional cycles of TAC or to four cycles of vinorelbine at 25 mg/m(2) and capecitabine at 2000 mg/m(2) (NX). The outcome was sonographic response, defined as a reduction in the product of the two largest perpendicular diameters by at least 50%. A difference of 10% or less in the sonographic response qualified as noninferiority of the NX treatment. Pathological complete response was defined as no invasive or in situ residual tumor masses in the breast and lymph nodes. Toxic effects were assessed. All statistical tests were two-sided. Of 2090 patients enrolled in the GeparTrio study, 622 (29.8%) who did not respond to two initial cycles of TAC were randomly assigned to an additional four cycles of TAC (n = 321) or to four cycles of NX (n = 301). Sonographic response rate was 50.5% for the TAC arm and 51.2% for the NX arm. The difference of 0.7% (95% confidence interval = -7.1% to 8.5%) demonstrated noninferiority of NX (P = .008). Similar numbers of patients in both arms received breast-conserving surgery (184 [57.3%] in the TAC arm vs 180 [59.8%] in the NX arm) and had a pathological complete response (5.3% vs 6.0%). Fewer patients in the NX arm than in the TAC arm had hematologic toxic effects, mucositis, infections, and nail changes, but more had hand-foot syndrome and sensory neuropathy. Pathological complete responses to both regimens were marginal. Among patients who did not respond to the initial neoadjuvant TAC treatment, similar efficacy but better tolerability was observed by switching to NX than continuing with TAC.
  CancerSpectrum Knowledge Environment 05/2008; 100(8):542-51. · 14.07 Impact Factor
• Article: Intensified neoadjuvant chemotherapy in early-responding breast cancer: phase III randomized GeparTrio study.

  Gunter von Minckwitz, Sherko Kümmel, Petra Vogel, Claus Hanusch, Holger Eidtmann, Jörn Hilfrich, Bernd Gerber, Jens Huober, Serban Dan Costa, Christian Jackisch, Sibylle Loibl, Keyur Mehta, Manfred Kaufmann
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  ABSTRACT: Patients with an early response to neoadjuvant chemotherapy have chemosensitive tumors and a high probability for a pathological complete response at surgery. The relationship between extended chemotherapy and pathological complete response at surgery was investigated in a clinical trial. Untreated breast cancer patients received two 3-week cycles of docetaxel at 75 mg/m(2), doxorubicin at 50 mg/m(2), and cyclophosphamide at 500 mg/m(2) (TAC). Those whose tumor size decreased by 50% or more by sonographic measurement (ie, reduction in the product of the two largest perpendicular diameters by at least 50%) were classified as responders and randomly assigned to receive four or six more cycles of TAC, for a total of six or eight TAC cycles. The primary aim was to increase the rate of a pathological complete response (defined as no invasive or in situ residual tumor masses in the breast and lymph nodes) from 20% to 26%. Sonographic response rates and rates of breast-conserving surgery and adverse effects were also assessed. All statistical tests were two-sided. Of the 2090 patients in the GeparTrio trial, 1390 (66.5%) were randomly assigned as responders after two initial TAC cycles to receive an additional four (n = 704) or six (n = 686) TAC cycles. Rates of pathological complete response were not statistically significantly different between the arms (21.0% with six TAC cycles and 23.5% with eight TAC cycles; difference = 2.5%, 95% confidence interval [CI] = -1.8% to 6.8%; P = .27). More clinical (48.2% vs 52.9%, difference = 4.7%; 95% CI = -0.55% to 9.95%; P = .08) and sonographic (22.6% vs 27.6%, difference = 5%; 95% CI = 0.45% to 9.55%; P = .033) complete responses at surgery were observed with eight TAC cycles than with six TAC cycles. The rate of breast-conserving surgery was similar in both arms (67.5% vs 68.5%, respectively, P = .68). Grade 3 or 4 leukopenia and edema and various grade 1 or 2 adverse events were more frequent in patients receiving eight TAC cycles than in those receiving six cycles. Patients receiving eight TAC cycles had statistically significantly higher sonographic response rates but not pathological complete response rates than those receiving six TAC cycles. However, they also had more toxic effects. So far, eight cycles of TAC cannot be recommended for the whole group of patients responding to two initial cycles of TAC.
  CancerSpectrum Knowledge Environment 05/2008; 100(8):552-62. · 14.07 Impact Factor
• Article: Treatment strategies that effectively reduce early recurrence risk in postmenopausal women with endocrine-sensitive breast cancer: AIs upfront vs. switching.

  Stefan Paepke, Volker R Jacobs, Ralf Ohlinger, Mathias Warm, Sherko Kümmel, Anke Thomas, Nadia Harbeck, Marion Kiechle-Bahat
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  ABSTRACT: Several large, well-controlled clinical trials have now established that the aromatase inhibitors (AIs), including letrozole, anastrozole, and exemestane, are more effective than tamoxifen when used as adjuvant endocrine therapy in postmenopausal women with breast cancer. Yet, it is an open question as to how these drugs should be best integrated into the adjuvant treatment regimen. Both letrozole and anastrozole have shown efficacy over tamoxifen when used as initial adjuvant therapy (initiated just following surgery for breast cancer), while exemestane and anastrozole have been used as switching adjuvant therapy, i.e., following 2-3 years of initial adjuvant tamoxifen therapy, with proven efficacy over continued tamoxifen. Studies demonstrate that recurrence risk peaks in the early period after surgery, and that distant metastases in particular, accounting for most of the early recurrences, have worse survival rates when compared with other types of recurrences. Treatments that reduce recurrences, especially distant metastases, in this early period are therefore likely to improve overall survival (OS) and reduce mortality from breast cancer. In this review, we discuss early recurrence risk among postmenopausal women with successfully treated early breast cancer, the efficacy of the different AIs in reducing early recurrences and distant metastases when incorporated into adjuvant therapy, and the evidence for increased OS when AIs are used as initial or switch adjuvant therapy.
  Journal of Cancer Research and Clinical Oncology 01/2008; 133(12):905-16. · 2.56 Impact Factor