Breast Neoplasms: Kühn T

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.

Bauerfeind I, Himsl I, Kühn T, Untch M, Hepp H. · Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe-Grosshadern, Ludwig-Maximilians-Universität München, Deutschland. · Gynakol Geburtshilfliche Rundsch. · Pubmed #15073437 No free full text.

Abstract: Axillary lymph node excision of level I and II with at least 10 lymph nodes is the operative gold standard for invasive breast cancer. Axillary lymph node excision is a diagnostic procedure for histopathologic tumor classification, for assessment of prognosis, local tumor control and adjuvant therapy decision. The sentinel node biopsy is a minimal-invasive procedure to determine the axillary lymph node status by excision of one or more sentinel nodes. This procedure is being increasingly implemented in breast cancer surgery. The classical axillary lymph node excision can be replaced by sentinel node biopsy if sentinel nodes are free of invasion in the intraoperative as well as in the final histopathological report. Sentinel node biopsy can become an operative routine procedure only in a quality-controlled environment.

Kühn T, Kreienberg R. · Frauenklinik Gifhorn. · Dtsch Med Wochenschr. · Pubmed #14961447 No free full text.

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Kühn T, Bembenek A, Büchels H, Decker T, Dunst J, Müllerleile U, Munz DL, Ostertag H, Sautter-Bihl ML, Schirrmeister H, Tulusan AH, Untch M, Winzer KJ, Wittekind C, Anonymous00228. · Frauenklinik und Projektgruppe interdisziplinäre Senologie Gifhorn, Bergstr. 30, 38518 Gifhorn. · Nuklearmedizin. · Pubmed #14978534 No free full text.

Abstract: The international consensus conference from St. Gallen concerning the treatment of early breast cancer concluded in 2003, that sentinel node biopsy was now accepted as method allowing axillary staging in breast cancer. This procedure may avoid complete lymph node dissection in appropriate cases. Since numerous questions associated with the technique are still not defined and the procedure itself is not yet standardized, the German Society of Senology defined the conditions for the routine clinical use of sentinel node biopsy in an interdisciplinary consensus meeting.

Buck A, Schirrmeister H, Kühn T, Shen C, Kalker T, Kotzerke J, Dankerl A, Glatting G, Reske S, Mattfeldt T. · Department of Nuclear Medicine, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm, Germany. · Eur J Nucl Med Mol Imaging. · Pubmed #12271413 No free full text.

Abstract: The aim of this study was to evaluate the possible correlation between preoperative FDG-PET results in human breast cancer and the prognostic markers Ki-67, c- erb B2, p53, oestrogen/progesterone receptor status, axillary lymph node status, tumour size and tumour grading. Seventy-five female patients with breast cancer were included in this prospective study. Patient selection was independent of tumour size and the suspected clinical stage of disease. A high-resolution full-ring scanner (Siemens ECAT HR+) was used for PET imaging. The FDG uptake of breast tumours was calculated as the tumour to background ratio (TBR). In resected cancer tissue specimens, the proliferative fraction was evaluated by Ki-67 immunostaining. Additionally, immunostaining of the prognostic markers c-erb B2, p53, and progesterone and oestrogen receptors was performed. Haematoxylin and eosin-stained sections were used for tumour grading. Correlations between FDG uptake and prognostic markers were assumed to be significant at P<0.05 using the Mann-Whitney U test. In ductal breast cancer, mean TBR was 17.3 (median 7.7, range 1.6-122.7), while in lobular cancer it was 6.5 (median 3.7, range 1.4-22.7). Mean proliferative fraction (% Ki-67 positive tumour cells) was 15%+/-13.8% (median 10%, range 0%-60%). Twenty-three carcinomas showed <5% Ki-67 positive tumour cells. Statistical analysis indicated a positive correlation between FDG uptake and proliferative index in ductal breast cancer ( P<0.0001, r=0.63). By contrast, there was no correlation between FDG uptake and c- erb B2 ( P=0.79), p53 ( P=0.92), tumour grading ( P=0.09), oestrogen receptor status ( P=0.41), progesterone receptor status ( P=0.34), axillary lymph node status ( P=0.90) and tumour size ( P=0.3). It is concluded that FDG uptake is significantly higher in ductal breast cancer than in lobular cancer ( P<0.05). FDG uptake correlates with proliferative activity assessed by Ki-67 immunostaining ( P<0.05). A significant correlation with the other prognostic markers, however, could not be demonstrated.

Schirrmeister H, Kühn T, Guhlmann A, Santjohanser C, Hörster T, Nüssle K, Koretz K, Glatting G, Rieber A, Kreienberg R, Buck AC, Reske SN. · Department of Nuclear Medicine, University Hospital, 89070 Ulm, Germany. · Eur J Nucl Med. · Pubmed #11315604 No free full text.

Abstract: The present study compared the diagnostic accuracy of fluorine-18 2-deoxy-2-fluoro-D-glucose positron emission tomography (FDG-PET) with conventional staging techniques. The differentiation between malignant and benign lesions and the detection of multifocal disease, axillary and internal lymph node involvement, and distant metastases were evaluated. One hundred and seventeen female patients were prospectively examined using FDG-PET and conventional staging methods such as chest X-ray, ultrasonography of the breast and liver, mammography and bone scintigraphy. All patients were examined on a modern full-ring PET scanner. Histopathological analysis of resected specimens was employed as the reference method. The readers of FDG-PET were blinded to the results of the other imaging methods and to the site of the breast tumour. The sensitivity and specificity of FDG-PET in detecting malignant breast lesions were 93% and 75% respectively. FDG-PET was twofold more sensitive (sensitivity 63%, specificity 95%) in detecting multifocal lesions than the combination of mammography and ultrasonography (sensitivity 32%, specificity 93%). Sensitivity and specificity of FDG-PET in detecting axillary lymph node metastases were 79% and 92% (41% and 96% for clinical evaluation). FDG-PET correctly indicated distant metastases in seven patients. False-positive or false-negative findings were not encountered with FDG-PET. Chest X-ray was false-negative in three of five patients with lung metastases. Bone scintigraphy was false-positive in four patients. Three patients were upstaged since FDG-PET detected distant metastases missed with the standard staging procedure. It is concluded that, compared with the imaging methods currently employed for initial staging, FDG-PET is as accurate in interpreting the primary tumour and more accurate in screening for lymph node metastases and distant metastases. Due to a false-negative rate of 20% in detecting axillary lymph node metastases, FDG-PET cannot replace histological evaluation of axillary status.

Kühn T, Santjohanser C, Koretz K, Böhm W, Kreienberg R. · Department of Gynecology and Obstetrics, University of Ulm, Prittwitzstrasse 43, 89079 Ulm, Germany. · Surg Endosc. · Pubmed #10890968 No free full text.

Abstract: BACKGROUND: Sentinel node biopsy is a promising technique that allows the axillary status of breast cancer patients to be predicted with high accuracy. Reducing false negative results remains a major challenge for the improvement of this procedure. Furthermore, new techniques are required to achieve axillary clearing with less morbidity in cases of unsuccessful mapping or multicentric carcinoma. We analyzed whether axilloscopy and endoscopic sentinel node biopsy is a feasible procedure for visualization of the axillary space and resection of the sentinel node using endoscopic techniques. METHODS: Following blue dye-guided lymphography and liposuction of the axillary fat, endoscopic axillary sentinel node biopsy was performed in 35 breast cancer patients. We then assessed the exposure of anatomical landmarks, the detection rate of the sentinel node, the false negative rate, and the accuracy of consecutive axillary clearing. RESULTS: In almost every case, an excellent anatomical orientation was achieved. The detection rate for the sentinel node was 83.3%. In one case, the sentinel node did not reflect the status of the residual axilla. A mean number of 17.1 lymph nodes was harvested at consecutive axillary clearing. CONCLUSIONS: Axilloscopy and endoscopic sentinel node biopsy, following liposuction of the axillary fat, is a feasible procedure that allows identification and minimally invasive resection of the sentinel node with high accuracy. The endoscopic approach might help to minimize the pitfalls of sentinel node biopsy by visualizing the axillary space. In future, it may become a technique that enables minimally invasive axillary clearing when complete lymphadenectomy is required.

Helms G, Kühn T, Moser L, Remmel E, Kreienberg R. · Universitätsfrauenklinik, Prittwitzstrasse 43, D-89075 Ulm, Germany. · Eur J Surg Oncol. · Pubmed #18838245 No free full text.

Abstract: BACKGROUND: Axillary lymph node dissection (ALND) as part of surgical treatment in breast cancer has been the standard procedure for many decades. However, patients frequently develop shoulder-arm morbidity postoperatively. Recently, sentinel node (SN) biopsy has been established as a new standard of care for axillary staging in breast cancer. This study compares postoperative morbidity between ALND and SN biopsy. The results are compared with the existing literature. METHOD: Between November 2000 and September 2002, 181 women with early stage breast cancer underwent primary surgery following preoperative randomisation into two groups, a "standard group" (SN biopsy was followed by ALND) and a study group (surgical procedure consisting of only SN biopsy when histologically metastasis-free SN was present). Follow-up data (362 sessions; 6 months to 3 years after primary surgery) were available from 150 patients. A summary morbidity score was calculated from four subjective (arm-strength, arm-mobility, arm swelling, pain) and four objective (arm-strength, arm-mobility, lymphedema, sensitivity) criteria. RESULTS: Fifty seven patients underwent SN biopsy only. Ninety three patients underwent ALND, 57 of which had lymph nodes free of metastasis and 36 had lymph nodes with metastasis and axillary clearing. Shoulder-arm morbidity was significantly different between the groups. Patients treated with SN biopsy only scored better on subjective and objective criteria. SUMMARY: Postsurgical shoulder-arm morbidity is a major long-term problem in patients undergoing surgical treatment for breast cancer. This prospective study showed significantly less severe shoulder-arm morbidity following SN biopsy compared to patients undergoing ALND.

Schirrmeister H, Kotzerke J, Vogl F, Buck A, Czech N, Koretz K, Helm G, Kreienberg R, Kühn T. · Department of Nuclear Medicine, University of Kiel, Germany. · Cancer Biother Radiopharm. · Pubmed #15665628 No free full text.

Abstract: OBJECTIVE: This prospective multicenter study was performed to assess the reliability of sentinel lymph node (SLN) biopsy in breast cancer and to analyze factors potentially influencing success rates. METHODS: In 21 departments, SLN biopsy and consecutive axillary lymph node dissection were performed in 814 breast cancer patients. The 80 surgeons involved were free in the choice of lymphography technique. The detection rate and the sensitivity, as well as the impact of lymphography technique, patient selection, technical procedure and learning curves, were evaluated. RESULTS: The blue dye technique was used in 137 patients, radiocolloid in 169 patients, and combined blue dye/radiocolloid in 508 patients. The identification rate for the sentinel node was 83.9% for the entire group and showed a significant dependence on the lymphography technique (blue dye, 71.6%; radiocolloid, 78.8%; combined blue dye and radiocolloid, 89.6%). The overall sensitivity in detecting lymph node metastases was 91.3%. Immunostaining for cytoceratine revealed micrometastases in 19 (5.1%) of 374 patients in whom H/E staining was negative. The combined subdermal/peritumoral injection of the colloid showed a significantly higher identification rate than subdermal or peritumoral injection alone (96.8%, 84.6%, 78.6%; p < 0.001). There was also a significant higher detection rate in cases of SLN biopsy performed prior to lumpectomy, compared to SLN biopsy following lumpectomy (94.7% versus 82.8%; p < 0.001). Furthermore, there was a close correlation between the number of performed examinations and the detection rate. CONCLUSION: SLN mapping predicts the axillary lymph node status accurately. Learning curves and several technical features influence the detection rate significantly. However, the false negative rate was independent of experience and injection technique.

Kühn T, Bembenek A, Büchels H, Decker T, Dunst J, Müllerleile U, Munz DL, Ostertag H, Sautter-Bihl ML, Schirrmeister H, Tulusan AH, Untch M, Winzer KJ, Wittekind C, Anonymous00124. · Frauenklinik und Projektgruppe interdisziplinäre Senologie, Gifhorn. · Pathologe. · Pubmed #15188789 No free full text.

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Rieber A, Brambs HJ, Gabelmann A, Heilmann V, Kreienberg R, Kühn T. · Department of Diagnostic Radiology, University of Ulm, Robert-Koch-Strasse 8, Germany. · Eur Radiol. · Pubmed #12111062 No free full text.

Abstract: The objective of the present study was to monitor response to preoperative chemotherapy with breast MRI in patients with large breast cancer. Fifty-eight women in whom core biopsy had confirmed the presence of breast carcinoma underwent breast MRI prior to beginning chemotherapy and before surgical excision. In 24 cases patients underwent one or two additional examinations during chemotherapy to monitor their progress. Breast MRI included both T2-weighted spin-echo sequences and T1-weighted gradient-echo sequences before and 1, 2, 3, and 8 min after bolus injection of gadolinium-DTPA. Tumor size and the dynamic contrast medium uptake patterns of the respective carcinomas were evaluated and compared with the final histology findings. Based on their MR tomographic findings (change in tumor size and intensity of contrast media uptake), patients were assigned to groups with non-response (NR), partial response (PR), and complete response (CR). Based on MR tomographic findings, there were 12 patients in the NR group, 34 in the PR group, and 12 in the CR group. In NR group contrast medium uptake tended to increase or show no more than minimal decrease. Diagnostic accuracy for assigning patients to the NR group was 83.3% and to the PR group 82.4%. In patients whose tumors showed only slight response to chemotherapy, breast MRI proved very reliable in determining the size of the lesions. In patients whose tumors displayed significant response and in the CR group, the size of the residual tumor was underestimated in 8 of 12 cases. In 66.7% of patients in the CR group histology revealed residual tumor masses in areas up to 5 cm in diameter. During chemotherapy, intensity of contrast medium uptake decreased in 88.2% of patients with PR and in all patients with CR. Reliable determination of response was possible within 6 weeks following the initiation of chemotherapy. Breast MRI is suitable as a monitoring method. The determination of residual tumor size is unreliable in carcinomas exhibiting significant response to chemotherapy which may lead to false-negative results. The method may be employed for monitoring response to chemotherapy after 6 weeks.

Heuser T, Rink T, Weller E, Fitz H, Zippel HH, Kreienberg R, Kühn T. · Department of Gynecology and Obstetrics, Municipal Hosptital Hanau, Germany. · Breast Cancer Res Treat. · Pubmed #11519861 No free full text.

Abstract: OBJECTIVE: The aim of this study is to analyze whether the axillary status influences the lymphatic mapping procedure in malignant breast disease and whether clinically relevant consequences for the technique of Sentinel Node (SN) biopsy may be drawn from this information. MATERIALS AND METHODS: SN biopsy was performed in 150 consecutive patients using a combination of the radioguided and the blue-dye technique. Axillary status was compared with the number of detected nodes. In cases of numerous nodes with tracer uptake, the radioactivity of each radiolabeled node was measured separately in a dose calibrator. We analyzed whether an increased tracer uptake could possibly indicate a 'true' or 'dominant' SN. Blue dye uptake was registered and compared with radioactivity. The findings were related to the histologic results. RESULTS: In patients with a positive axillary status, significantly more radiolabeled nodes were detected than in node negative patients (median 3 vs. 2; p < 0.001). In 54/86 patients with numerous SNs a 'dominant' node with at least twice the radioactivity than other marked nodes could be identified (62.8%). From 26 cases with axillary involvement, 20 patients (76.9%) were identified by the 'dominant' and the remaining six women (23.1%) by others than the seemingly leading SN. CONCLUSION: Axillary lymph node involvement influences the drainage pattern in breast cancer. Patients with numerous SNs have an increased risk of axillary involvement. A high tracer uptake does not permit the identification of a 'true' SN. A lack of surgical accuracy may lead to pitfalls if the axilla is not screened carefully for all radioactive nodes.

Rieber A, Kühn T, Nüssle K, Brambs HJ. · Abteilung für Röntgendiagnostik, Universität Ulm. · Rontgenpraxis. · Pubmed #11341015 No free full text.

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Schirrmeister H, Guhlmann A, Kotzerke J, Santjohanser C, Kühn T, Kreienberg R, Messer P, Nüssle K, Elsner K, Glatting G, Träger H, Neumaier B, Diederichs C, Reske SN. · Departments of Nuclear Medicine, Gynecology, Radiation Oncology, and Diagnostic Radiology, University Hospital, Ulm, Germany. · J Clin Oncol. · Pubmed #10561300 No free full text.

Abstract: PURPOSE: Previous studies have shown that bone metastases are revealed by magnetic resonance imaging (MRI) or bone marrow scintigraphy several months before they are visible by conventional bone scintigraphy (BS). We present a new approach for detecting bone metastases in patients with breast cancer. We compared findings obtained with fluoride ion (F-18) and positron emission tomography (PET) with those obtained with conventional BS. PATIENTS AND METHODS: Thirty-four breast cancer patients were prospectively examined using F-18-PET and conventional BS. F-18-PET and BS were performed within 3 weeks of each other. Metastatic bone disease was previously known to be present in six patients and was suspected (bone pain or increasing levels of tumor markers, Ca(2+), alkaline phosphatase) in 28 patients. Both imaging modalities were compared by patient-by-patient analysis and lesion-by-lesion analysis, using a five-point scale for receiver operating characteristic (ROC) curve analysis. A panel of reference methods was used, including MRI (28 patients), planar x-ray (17 patients), and spiral computed tomography (four patients). RESULTS: With F-18-PET, 64 bone metastases were detected in 17 patients. Only 29 metastases were detected in 11 patients with BS. As a result of F-18-PET imaging, clinical management was changed in four patients (11.7%). For F-18-PET, the area under the ROC curve was 0.99 on a lesion basis (for BS, it was 0.74; P <.05) and 1.00 on a patient basis (for BS, it was 0.82; P <.05). CONCLUSION: F-18-PET demonstrates a very early bone reaction when small bone marrow metastases are present, allowing accurate detection of breast cancer bone metastases. This accurate detection has a significant effect on clinical management, compared with the effect on management brought about by detection with conventional BS.

Kühn T, Santjohanser C, Koretz K, Böhm W, Kreienberg R. · Universitätsfrauenklinik Ulm. · Zentralbl Gynakol. · Pubmed #10096174 No free full text.

Abstract: OBJECTIVE: Assessment of axillary nodal status with reduced shoulder-arm-morbidity remains a major challenge for primary surgery of breast cancer patients. In a pilot study endoscopic axillary lymph node dissection was evaluated. MATERIAL AND METHODS: In 30 breast cancer patients axillary lymphadenectomy was performed after liposuction using an endoscopic approach. During a learning phase of 15 cases an open revision was routinely carried out. Later complete endoscopic lymph node dissection was performed. The exposition of anatomical landmarks, the number of resected lymph nodes, postoperative lymphorrhea, histopathological signs of traumatisation were assessed as well as intra and postoperative complications. RESULTS: In any case we found excellent exposure of anatomical landmarks. Following a learning curve of 15 cases the average number of resected lymph nodes was equal to the average number of lymph nodes resected with conventional techniques (18.2 vs. 18.4, median 17 vs 18). Minimal intraoperative complications were observed. Postoperative lymphorrhea and seroma rate were not remarkably reduced in comparison with open procedures. CONCLUSIONS: Our study demonstrates, that endoscopic lymph node dissection may be performed with a low complication rate and with identical accuracy as achieved by open techniques.