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104. Irene von Treskow. Die Jugendstil-Porzellane der KPM. Bestandskatalog der Königlichen Porzellan-Manufaktur 1860- 1914

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Irene von Treskow. Die Jugendstil-Porzellane der KPM. Bestandskatalog der Königlichen Porzellan-Manufaktur 1860- 1914. München (Prestel Verlag) 1971. 340 S.; 354 Abb. auf Taf., davon 55 farbig; über 500 Strichätzungen., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Vol. 25 No. 6 (1972): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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105. 441P Real-world efficacy of ribociclib (RIB) + aromatase inhibitor (AI)/fulvestrant (FUL) in subgroups of special interest: 5th interim analysis (IA) of the RIBANNA study

Author

Woeckel, A., Brucker, C., Decker, T., Fasching, P., Göhler, T., Jackisch, C., Janssen, J., Koehler, A., Luedtke-Heckenkamp, K., D. Lüftner, Van Mackelenbergh, M., Marmé, F., Nusch, A., Rautenberg, B., Reimer, T., Weide, R., Wimberger, P., Maslanka Figueroa, S., Roos, C., and Schmidt, M.

Published
2023
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106. 409P Treatment of elderly patients (pts; > 75 years) with 1st-line ribociclib (RIB) + endocrine therapy (ET) or endocrine monotherapy in clinical routine: Real-world data from the RIBANNA study (5th interim analysis (IA))

Author

Decker, T., Brucker, C., Fasching, P., Göhler, T., Jackisch, C., Janssen, J., Koehler, A., Luedtke-Heckenkamp, K., D. Lüftner, Van Mackelenbergh, M., Marmé, F., Nusch, A., Rautenberg, B., Reimer, T., Schmidt, M., Weide, R., Wimberger, P., Maslanka Figueroa, S., Roos, C., and Woeckel, A.

Published
2023
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107. 411P Therapy management and safety of 1st-line ribociclib (RIB) + aromatase inhibitor (AI)/fulvestrant (FUL) in clinical routine: Real-world data from the RIBANNA study (5th interim analysis (IA))

Author

Marmé, F., Brucker, C., Decker, T., Fasching, P., Göhler, T., Jackisch, C., Janssen, J., Koehler, A., Luedtke-Heckenkamp, K., D. Lüftner, Van Mackelenbergh, M., Nusch, A., Rautenberg, B., Schmidt, M., Reimer, T., Weide, R., Wimberger, P., Maslanka Figueroa, S., Roos, C., and Woeckel, A.

Published
2023
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108. AGO Recommendations for the Surgical Therapy of the Axilla After Neoadjuvant Chemotherapy: 2021 Update

Author

Friedrich, Michael, Kuehn, Thorsten, Janni, Wolfgang, Mueller, Volkmar, Banys-Pachulowski, Maggie, Kolberg-Liedtke, Cornelia, Jackisch, Christian, Krug, David, Albert, Ute-Susann, Bauerfeind, Ingo, Blohmer, Jens, Budach, Wilfried, Dall, Peter, Fallenberg, Eva M., Fasching, Peter A., Fehm, Tanja, Gerber, Bernd, Gluz, Oleg, Hanf, Volker, Harbeck, Nadia, Heil, Joerg, Huober, Jens, Kreipe, Hans-Heinrich, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael Patrick, Maass, Nicolai, Moebus, Volker, Mundhenke, Christoph, Nitz, Ulrike, Park-Simon, Tjoung-Won, Reimer, Toralf, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schuetz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Witzel, Isabell, Woeckel, Achim, Thill, Marc, Ditsch, Nina, Friedrich, Michael, Kuehn, Thorsten, Janni, Wolfgang, Mueller, Volkmar, Banys-Pachulowski, Maggie, Kolberg-Liedtke, Cornelia, Jackisch, Christian, Krug, David, Albert, Ute-Susann, Bauerfeind, Ingo, Blohmer, Jens, Budach, Wilfried, Dall, Peter, Fallenberg, Eva M., Fasching, Peter A., Fehm, Tanja, Gerber, Bernd, Gluz, Oleg, Hanf, Volker, Harbeck, Nadia, Heil, Joerg, Huober, Jens, Kreipe, Hans-Heinrich, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael Patrick, Maass, Nicolai, Moebus, Volker, Mundhenke, Christoph, Nitz, Ulrike, Park-Simon, Tjoung-Won, Reimer, Toralf, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schuetz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Witzel, Isabell, Woeckel, Achim, Thill, Marc, and Ditsch, Nina

Abstract

For many decades, the standard procedure to treat breast cancer included complete dissection of the axillary lymph nodes. The aim was to determine histological node status, which was then used as the basis for adjuvant therapy, and to ensure locoregional tumour control. In addition to the debate on how to optimise the therapeutic strategies of systemic treatment and radiotherapy, the current discussion focuses on improving surgical procedures to treat breast cancer. As neoadjuvant chemotherapy is becoming increasingly important, the surgical procedures used to treat breast cancer, whether they are breast surgery or axillary dissection, are changing. Based on the currently available data, carrying out SLNE prior to neoadjuvant chemotherapy is not recommended. In contrast, surgical axillary management after neoadjuvant chemotherapy is considered the procedure of choice for axillary staging and can range from SLNE to TAD and ALND. To reduce the rate of false negatives during surgical staging of the axilla in pN+(CNB) stage before NACT and ycN0 after NACT, targeted axillary dissection (TAD), the removal of > 2 SLNs (SLNE, no untargeted axillary sampling), immunohistochemistry to detect isolated tumour cells and micro-metastases, and marking positive lymph nodes before NACT should be the standard approach. This most recent update on surgical axillary management describes the significance of isolated tumour cells and micro-metastasis after neoadjuvant chemotherapy and the clinical consequences of low volume residual disease diagnosed using SLNE and TAD and provides an overview of this year's AGO recommendations for surgical management of the axilla during primary surgery and in relation to neoadjuvant chemotherapy.

Published
2021

109. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021

Author

Ditsch, Nina, Kolberg-Liedtke, Cornelia, Friedrich, Michael, Jackisch, Christian, Albert, Ute-Susann, Banys-Paluchowski, Maggie, Bauerfeind, Ingo, Blohmer, Jens-Uwe, Budach, Wilfried, Dall, Peter, Fallenberg, Eva M., Fasching, Peter A., Fehm, Tanja, Gerber, Bernd, Gluz, Oleg, Harbeck, Nadia, Heil, Jorg, Huober, Jens, Kreipe, Hans-Heinrich, Krug, David, Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael P., Maass, Nicolai, Mundhenke, Christoph, Nitz, Ulrike, Park-Simon, Tjoung-Won, Reimer, Toralf, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schutz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Witzel, Isabell, Woeckel, Achim, Mueller, Volkmar, Janni, Wolfgang, Thill, Marc, Ditsch, Nina, Kolberg-Liedtke, Cornelia, Friedrich, Michael, Jackisch, Christian, Albert, Ute-Susann, Banys-Paluchowski, Maggie, Bauerfeind, Ingo, Blohmer, Jens-Uwe, Budach, Wilfried, Dall, Peter, Fallenberg, Eva M., Fasching, Peter A., Fehm, Tanja, Gerber, Bernd, Gluz, Oleg, Harbeck, Nadia, Heil, Jorg, Huober, Jens, Kreipe, Hans-Heinrich, Krug, David, Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael P., Maass, Nicolai, Mundhenke, Christoph, Nitz, Ulrike, Park-Simon, Tjoung-Won, Reimer, Toralf, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schutz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Witzel, Isabell, Woeckel, Achim, Mueller, Volkmar, Janni, Wolfgang, and Thill, Marc

Published
2021

110. Real-world efficacy of ribociclib (RIB) plus aromatase inhibitor (AI)/fulvestrant (FUL), or endocrine monotherapy (ET), or chemotherapy (CT) as first-line (1L) treatment (tx) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Results of fourth interim analysis (IA) from RIBANNA

Author

Diana Lüftner, Cosima Brucker, Thomas Decker, Peter A. Fasching, Thomas Göhler, Christian Jackisch, Jan Janssen, Andreas Koehler, Kerstin Luedtke-Heckenkamp, Marion Van Mackelenbergh, Frederik Marmé, Arnd Nusch, Beate Rautenberg, Toralf Reimer, Marcus Schmidt, Rudolf Weide, Pauline Wimberger, Naiba Nabieva, Christian Roos, and Achim Woeckel

Subjects
Cancer Research, Oncology
Abstract

1065 Background: RIBANNA is a real-world, noninterventional study conducted in Germany evaluating efficacy, safety, and tolerability of RIB in combination with AI/FUL aiming to gain insights into routine clinical practice for pts with HR+, HER2– ABC. Here, we present results of the fourth IA from RIBANNA. Methods: Pre-, peri- and postmenopausal pts who received 1L tx with RIB+AI/FUL, or ET or CT for HR+, HER2– ABC were included in accordance with the German tx guideline. The effect of baseline demographic characteristics, including histological grade, age, previous adjuvant tx, Eastern Cooperative Oncology Group-performance score (ECOG-PS), and metastatic sites on progression-free survival was evaluated using Cox regression model. Results: At data cutoff October 11, 2021, 2598 pts were enrolled in the study (RIB+AI/FUL, n = 2177; ET, n = 239; CT, n = 182). Data from 1L tx were available for 2492 pts (95.9%), second-line tx for 689 pts (26.5%), third-line tx for 263 pts (10.1%), and fourth-line tx for 94 pts (3.6%). Significant differences were observed in baseline mean age and metastatic sites for pts in RIB+AI/FUL cohort vs ET and CT cohorts (both < 0.001). At baseline, the mean (SD) ages of pts were 65.5 (11.6), 70.7 (11.5) and 61.6 (11.6) years in RIB+AI/FUL, ET, and CT cohorts, respectively. While comparing the performance status, 44.2% of pts in RIB+AI/FUL, 34.7% of pts in ET and 42.1% of pts in CT cohort were fully active with ECOG-PS = 0. CNS, liver, or lung metastases were recorded in 42.6% of pts in RIB+AI/FUL, 26.8% of pts in ET and 67.1% of pts in CT cohort. Bone only metastases were reported in 30.8%, 47.9% and 15.0% of pts in RIB+AI/FUL, ET, and CT cohorts, respectively. Overall, 32.1%, 37.7%, and 52.7% of pts discontinued the study in RIB+AI/FUL, ET, and CT cohorts, respectively, the most common reasons being deaths (16.1%,17.2%, and 31.9%, respectively) and lost to follow-up (5.9%, 8.8%, and 9.3%, respectively). The most common tx-emergent adverse event (grade 3 or 4) observed in RIB+AI/FUL cohort was neutropenia (14.8%), while 6.6% and 6.9% of pts in ET and CT cohorts, respectively, experienced neutropenia. The efficacy results from all 3 cohorts, including Kaplan-Meier curves, will be presented during ASCO 2022. Conclusions: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. Overall higher number of pts were treated in 1L with RIB+AI/FUL followed by ET and CT. The differences in baseline characteristics on metastatic pattern, age, and ECOG-PS reflect different selection strategies for 1L tx decision. No new safety signals were identified. Clinical trial information: CLEE011ADE03.

Published
2022
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116. Case reports of genital tract tumours in cows

Author

Martz, Paula, primary, Oezcan-Martz, Aycan, additional, Bittner, Lilli, additional, Ebert, Fanny, additional, Wippermann, Wolf, additional, Woeckel, Adriana, additional, Boettcher, Denny, additional, Baumgartner, Walter, additional, and Starke, Alexander, additional

Published
2020
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122. Adelheid Unger, Joseph Götsch. Ein bayerischer Bildhauer des Rokoko aus Tirol

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Adelheid Unger, Joseph Götsch. Ein bayerischer Bildhauer des Rokoko aus Tirol. Weissenhorn, Verlag Anton H. Konrad, 1972, 136 S., 154 Schwarz-Weiß-Abb., 4 Taf. im Text, 2 geogr. Übersichtstaf., 1 Stammtafel. DM 48,—., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 27 Nr. 12 (1974): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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123. Hans und Gertrude Aurenhammer. Das Belvedere in Wien, Bauwerk - Menschen - Geschichte

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Hans und Gertrude Aurenhammer. Das Belvedere in Wien, Bauwerk - Menschen - Geschichte. Veröffentlichung der Österreichischen Galerie. 8 Farbtafeln, 132 Schwarz-Weiß-Abbildungen. Kartoniert. Verlag Anton Schroll & Co. Wien und München 1971., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 26 Nr. 8 (1973): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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124. Konrad Strauss, Die Geschichte der Töpferkunst vom Mittelalter bis zur Neuzeit und die Kunsttöpfereien in Alt-Livland (Estland und Lettland)

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Konrad Strauss, Die Geschichte der Töpferkunst vom Mittelalter bis zur Neuzeit und die Kunsttöpfereien in Alt-Livland (Estland und Lettland). P. H. Heitz-Verlag. Basel 1969. 272 S. mit 2 Abb. im Text, 148 Abb. auf Taf., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 26 Nr. 4 (1973): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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125. Ernst Guldan, Wolfgang Andreas Heindl

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Ernst Guldan, Wolfgang Andreas Heindl. 185 Seiten Text, 4 Farbtafeln, 58 Schwarz-Weiß-Abbildungen. Leinen. Wien - München 1970. DM 95., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 26 Nr. 1 (1973): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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127. Katalog des Germanischen Nationalmuseums in Nürnberg: Die deutschen Handzeichnungen in Nürnberg Band IV

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Katalog des Germanischen Nationalmuseums in Nürnberg: Die deutschen Handzeichnungen in Nürnberg Band IV. Bearbeitet von Monika Heffels. Nürnberg 1969, 396 S., 5 Farbtaf., 465 Abb. im Text., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Bd. 23 Nr. 9 (1970): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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128. Konrad Strauss, Die Kachelkunst des 15. und 16. Jahrhunderts in Deutschland, Österreich und der Schweiz

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Konrad Strauss, Die Kachelkunst des 15. und 16. Jahrhunderts in Deutschland, Österreich und der Schweiz. Straßburg (Ed. Heitz) 1966. 160 S., 1 Farbtaf. und 82 Schwarzweißtaf., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Vol. 20 No. 9 (1967): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2020
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129. Differentiation between ischemic and hemorrhagic strokes: a pilot study with transtemporal investigation of brain parenchyma elasticity using ultrasound shear wave elastography

Author

Christoph Maurer, Michael Ertl, and Margarethe Woeckel

Subjects
Adult, medicine.medical_specialty, Neurology, Pilot Projects, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, Lesion, 03 medical and health sciences, Elasticity Imaging Techniques, 0302 clinical medicine, Parenchyma, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Prospective Studies, Acoustic radiation force, Shear wave elastography, medicine.diagnostic_test, business.industry, Ultrasound, Brain, Reproducibility of Results, Elasticity, Hemorrhagic Stroke, Elastography, medicine.symptom, business, Nuclear medicine, 030217 neurology & neurosurgery
Abstract

Ultrasound shear wave elastography is well established in diagnostics of several parenchymatous organs and is recommended by respective guidelines. So far, research about applications in relevant neurological conditions is missing, especially in adults. Here we aimed to examine the method for the differentiation of ischemic (IS) and hemorrhagic strokes (HS) and cerebral mass effects. 50 patients with a confirmed diagnosis of HS or IS were enrolled in this prospective study. 2D shear wave elastography was performed on the ipsilateral and the contralateral side with a modified acoustic radiation force impulse (ARFI) technique (ElastPQ mode, Philips). Lesion volumetry was conducted based on computed tomography data for correlation with elastography results. Elastography measurements (EM) revealed a highly significant difference between IS and HS with mean values of 1.94 and 5.50 kPa, respectively (p 0.00 001). Mean values of brain tissue on the non-affected side were almost identical (IS 3.38 (SD = 0.63); HS 3.35 (SD = 0.66); p = 0.91). With a sensitivity of 0.98 and a specificity of 0.99, a cut-off value of 3.52 kPa for discrimination could be calculated. There was a significant correlation of mass effect represented by midline shift and EM values on the contralateral side (Pearson correlation coefficient = 0.68, p 0.0003). Ultrasound brain parenchyma elastography seems to be a reliable sonographic method for discriminating between large IS and HS and for detecting and tracking conditions of intracerebral mass effects. Die Ultraschall-Scherwellen-Elastografie ist bereits eine im klinischen Alltag etablierte Diagnostik für verschiedene parenchymatöse Organe und wird von den entsprechenden Leitlinien empfohlen. Bislang gibt es jedoch keine relevante Forschung zur Anwendung bei neurologischen Erkrankungen, insbesondere bei Erwachsenen. In der vorliegenden Arbeit wurde daher der Stellenwert zur Differenzierung von ischämischen (IS) und hämorrhagischen Schlaganfällen (HS) und bei intrazerebralen Masseneffekten untersucht. Es wurden 50 Patienten mit einem nachgewiesenen HS oder IS in diese prospektive Studie eingeschlossen. Eine 2D-Scherwellen-Elastografie wurde auf der ipsi- und kontralateralen Seite mittels einer modifizierten „acoustic radiation force impulse“ (ARFI)-Technik (ElatPQ-Modus, Philips) durchgeführt. Eine Computertomografie-basierte Läsionsvolumetrie zur Korrelation mit den Elastografiewerten wurde ergänzt. Die Elastografiemessungen (EM) zeigten hochsignifikant unterschiedliche Ergebnisse zwischen IS und HS mit jeweiligen Mittelwerten von 1,94 und 5,50 kPa (p 0,00 001). Die Mittelwerte auf der nicht betroffenen Seite waren dabei nahezu identisch (IS 3,38 (SD = 0,63); HS 3,35 (SD = 0,66); p = 0,91). Mit einer Sensitivität von 98 % und einer Spezifität von 99 % konnte ein Cut-off-Wert von 3,52 kPa für die Differenzierung herausgearbeitet werden. Es zeigte sich außerdem eine signifikante Korrelation zwischen Masseneffekten im Sinne einer Mittellinienverlagerung und den EM auf der kontralateralen Seite (Pearson-Korrelationskoeffizient 0,68; p 0,0003). Die Ultraschall-Scherwellen-Elastografie erweist sich als verlässliche Methode zur Unterscheidung von IS und HS und zur Erfassung und Nachbeobachtung intrazerebraler Masseneffekte.

Published
2020

130. Effect of adjuvant radiotherapy in elderly patients with breast cancer

Author

Daniel Herr, Elena Leinert, Tanja Nadine Stueber, J Diessner, Wolfgang Janni, Manfred Wischnewsky, Achim Woeckel, Rolf Kreienberg, and Catharina Bartmann

Subjects
Oncology, medicine.medical_treatment, Cancer Treatment, Mastectomy, Segmental, Elderly, 0302 clinical medicine, Risk Factors, Breast Tumors, Medicine and Health Sciences, Breast-conserving surgery, 030212 general & internal medicine, skin and connective tissue diseases, Mastectomy, Aged, 80 and over, Multidisciplinary, Pharmaceutics, Hormonal Therapy, Combined Modality Therapy, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Hormonal therapy, Medicine, Female, Research Article, Clinical Oncology, medicine.medical_specialty, Science, Radiation Therapy, Breast Neoplasms, Surgical and Invasive Medical Procedures, Disease-Free Survival, 03 medical and health sciences, Breast cancer, Drug Therapy, Internal medicine, Breast Cancer, medicine, Humans, Survival analysis, Aged, Surgical Excision, business.industry, Cancers and Neoplasms, medicine.disease, Comorbidity, Log-rank test, Radiation therapy, Geriatrics, Age Groups, People and Places, Radiotherapy, Adjuvant, Population Groupings, Neoplasm Recurrence, Local, Clinical Medicine, business
Abstract

Background Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Although RT is routinely used following breast conserving surgery (BCS), patients may occasionally be effectively treated with BCS alone. Currently, the selection of patients undergoing BCS who do not need breast irradiation is under investigation. With the advancement of personalized medicine, there is an increasing interest in reduction of aggressive treatments especially in older women. The primary objective of this study was to identify elderly patients who may forego breast irradiation after BCS without measurable consequences on local tumor growth and survival. Methods We analyzed 2384 early breast cancer patients aged 70 and older who were treated in 17 German certified breast cancer centers between 2001 and 2009. We compared RT versus no RT after guideline adherent (GA) BCS. The outcomes studied were breast cancer recurrence (RFS) and breast cancer-specific survival (BCSS). Low-risk patients were defined by luminal A, tumor size T1 or T2 and node-negative whereas higher-risk patients were defined by patients with G3 or T3/T4 or node-positive or other than Luminal A tumors. To test if there is a difference between two or more survival curves, we used the Gp family of tests of Harrington and Fleming. Results The median age was 77 yrs (mean 77.6±5.6 y) and the median observation time 46 mths (mean 48.9±24.8 mths). 950 (39.8%) patients were low-risk and 1434 (60.2%) were higher-risk. 1298 (54.4%) patients received GA BCS of which 85.0% (1103) received GA-RT and only 15% (195) did not. For low-risk patients with GA-BCS there were no significant differences in RFS (log rank p = 0.651) and in BCSS (p = 0.573) stratified by GA-RT. 5 years RFS in both groups were > 97%. For higher-risk patients with GA-BCS we found a significant difference (p

Published
2020

131. Hans Aurenhammer, Martino Altomonte. Mit einem Beitrag 'Martino Altomonte als Zeichner und Graphiker' von Gertrude Aurenhammer / Brigitte Heinzl, Bartolomeo Altomonte

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Hans Aurenhammer, Martino Altomonte. Mit einem Beitrag .Martino Altomonte als Zeichner und Graphiker" von Gertrude Aurenhammer, Wien - München (Verlag Herold) 1965. 207 S., 78 Abb., 6 Farbtaf. Brigitte Heinzl, Bartolomeo Altomonte. Wien-München (Verlag Herold) 1964. 103 S., 55 Abb., 6 Farbtaf., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Vol. 20 No. 2 (1967): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2019
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132. Klaus Lankheit, Die Zeichnungen des kurpfälzischen Hofbildhauers Paul Egell (1691—1752)

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Klaus Lankheit, Die Zeichnungen des kurpfälzischen Hofbildhauers Paul Egell (1691—1752). Karlsruhe, G. Braun, 1954. 120 S. 52Taf. Offset und 24 Abb. auf Kunstdruck. Ganzleinen, in gr. 8°., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Vol. 8 No. 2 (1955): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2019
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133. Eugen Kusch, Unvergängliches Nürnberg

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Eugen Kusch, Unvergängliches Nürnberg. Nürnberg 1953, Verlag Hans Carl, Gr. 8°, 160 S., 126 Abb. DM 18.50., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Vol. 6 No. 12 (1953): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2019
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134. Margarete Baur-Heinhold, Fassadenmalerei. Ihre Entwicklung in Süddeutschland vom Mittelalter bis zur Gegenwart

Author

Woeckel, Gerhard Paulus

Abstract

Rezension zu: Margarete Baur-Heinhold, Fassadenmalerei. Ihre Entwicklung in Süddeutschland vom Mittelalter bis zur Gegenwart. München (1952): G. D. W. Callwey. 166 S., 148 Abb., 2 Farbtf. DM 25.—., Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege, Vol. 6 No. 1 (1953): Kunstchronik. Monatsschrift für Kunstwissenschaft, Museumswesen und Denkmalpflege

Published
2019
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135. Breast cancer risk inBRCA1/2mutation carriers and noncarriers under prospective intensified surveillance

Author

Engel, Christoph, Fischer, Christine, Zachariae, Silke, Bucksch, Karolin, Rhiem, Kerstin, Giesecke, Jutta, Herold, Natalie, Wappenschmidt, Barbara, Huebbel, Verena, Maringa, Monika, Reichstein-Gnielinski, Simone, Hahnen, Eric, Bartram, Claus R., Dikow, Nicola, Schott, Sarah, Speiser, Dorothee, Horn, Denise, Fallenberg, Eva M., Kiechle, Marion, Quante, Anne S., Vesper, Anne-Sophie, Fehm, Tanja, Mundhenke, Christoph, Arnold, Norbert, Leinert, Elena, Just, Walter, Siebers-Renelt, Ulrike, Weigel, Stefanie, Gehrig, Andrea, Woeckel, Achim, Schlegelberger, Brigitte, Pertschy, Stefanie, Kast, Karin, Wimberger, Pauline, Briest, Susanne, Loeffler, Markus, Bick, Ulrich, Schmutzler, Rita K., Engel, Christoph, Fischer, Christine, Zachariae, Silke, Bucksch, Karolin, Rhiem, Kerstin, Giesecke, Jutta, Herold, Natalie, Wappenschmidt, Barbara, Huebbel, Verena, Maringa, Monika, Reichstein-Gnielinski, Simone, Hahnen, Eric, Bartram, Claus R., Dikow, Nicola, Schott, Sarah, Speiser, Dorothee, Horn, Denise, Fallenberg, Eva M., Kiechle, Marion, Quante, Anne S., Vesper, Anne-Sophie, Fehm, Tanja, Mundhenke, Christoph, Arnold, Norbert, Leinert, Elena, Just, Walter, Siebers-Renelt, Ulrike, Weigel, Stefanie, Gehrig, Andrea, Woeckel, Achim, Schlegelberger, Brigitte, Pertschy, Stefanie, Kast, Karin, Wimberger, Pauline, Briest, Susanne, Loeffler, Markus, Bick, Ulrich, and Schmutzler, Rita K.

Abstract

Comparably little is known about breast cancer (BC) risks in women from families tested negative forBRCA1/2mutations despite an indicative family history, as opposed toBRCA1/2mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers ofBRCA1/2mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n= 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n= 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) forBRCA1mutation carriers, 43.2% (95% CI 32.1-56.3%) forBRCA2mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) forBRCA1mutation carriers, 13.5 (95% CI 9.2-19.1) forBRCA2mutation carriers and 4.9 (95% CI 3.8-6.3) forBRCA1/2noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) forBRCA1mutation carriers, 6.6% (95% CI 3.4-12.5%) forBRCA2mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women fromBRCA1/2negative families with elevated risk.

Published
2020

136. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2020

Author

Ditsch, Nina, Untch, Michael, Kolberg-Liedtke, Cornelia, Jackisch, Christian, Krug, David, Friedrich, Michael, Janni, Wolfgang, Mueller, Volkmar, Albert, Ute-Susann, Banys-Paluchowski, Malgorzata, Bauerfeind, Ingo, Blohmer, Jens-Uwe, Budach, Wilfried, Dall, Peter, Diel, Ingo, Fallenberg, Eva Maria, Fasching, Peter A., Fehm, Tanja, Gerber, Bernd, Gluz, Oleg, Hanf, Volker, Harbeck, Nadia, Heil, Joerg, Huober, Jens, Kreipe, Hans H., Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael, Maass, Nicolai, Moebus, Volker, Mundhenke, Christoph, Park-Simon, Tjoung-Won, Reimer, Toralf, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Solbach, Chistine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Witzel, Isabell, Woeckel, Achim, Thill, Marc, Ditsch, Nina, Untch, Michael, Kolberg-Liedtke, Cornelia, Jackisch, Christian, Krug, David, Friedrich, Michael, Janni, Wolfgang, Mueller, Volkmar, Albert, Ute-Susann, Banys-Paluchowski, Malgorzata, Bauerfeind, Ingo, Blohmer, Jens-Uwe, Budach, Wilfried, Dall, Peter, Diel, Ingo, Fallenberg, Eva Maria, Fasching, Peter A., Fehm, Tanja, Gerber, Bernd, Gluz, Oleg, Hanf, Volker, Harbeck, Nadia, Heil, Joerg, Huober, Jens, Kreipe, Hans H., Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael, Maass, Nicolai, Moebus, Volker, Mundhenke, Christoph, Park-Simon, Tjoung-Won, Reimer, Toralf, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Solbach, Chistine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Witzel, Isabell, Woeckel, Achim, and Thill, Marc

Published
2020

139. Liberal transfusion strategy to prevent mortality and anaemia-associated, ischaemic events in elderly non-cardiac surgical patients – the study design of the LIBERAL-Trial

Author

Meybohm, Patrick, Lindau, Simone, Treskatsch, Sascha, Francis, Roland, Spies, Claudia, Velten, Markus, Wittmann, Maria, Gueresir, Erdem, Stoppe, Christian, Kowark, Ana, Coburn, Mark, Selleng, Sixten, Baschin, Marcel, Jenichen, Gregor, Meersch, Melanie, Ermert, Thomas, Zarbock, Alexander, Kranke, Peter, Kredel, Markus, Helf, Antonia, Laufenberg-Feldmann, Rita, Ferner, Marion, Wittenmeier, Eva, Gürtler, Karl-Heinz, Kienbaum, Peter, De Abreu, Marcel Gama, Sander, Michael, Bauer, Michael, Seyfried, Timo, Gruenewald, Matthias, Choorapoikayil, Suma, Mueller, Markus M., Seifried, Erhard, Brosteanu, Oana, Bogatsch, Holger, Hasenclever, Dirk, Zacharowski, Kai, LIBERAL Collaboration Group, Baron, David, Grottke, Oliver, Hill, Aileen, Van Waesberghe, Julia, Ziemann, Sebastian, Tingart, Markus, Van Essen, Julius, Spring, Oliver, Pirzer, Raphael, Jaschinski, Ulrich, Heller, Axel R., Ertmer, Martin, Falk, Elke, Pickerodt, Philipp, Schiemann, Alexander, Schmidt, Katrin, Tafelski, Sascha, Trauzeddel, Ralf-Felix, Perka, Carsten, Ehrentraut, Heide, Fingehut, Louise, Hopf, Andreas, Guttenthaler, Vera, Neumann, Claudia, Osberghaus, Isabelle, Schuss, Patrick, Winkler, Anja, Kohlhof, Hendrik, Wirtz, Dieter C., Kalb, Robert, Hinterberg, Jonas, Schäfer, Maximilian, Koch, Thea, Piekarski, Florian, Tanner, Linda, Berg, Kira, Wiedenbeck, Carolin, Maushagen, Isabell, Zeisset, Daniela, Fuellenbach, Christoph, Westphal, Sabine, Pfeiffer, Sophia, Schnitzbauer, Andreas, Marzi, Ingo, Becker, Andreas, Ghanaati, Shahram, Schmitz-Rixen, Thomas, Brixner, Verena, Geisen, Christof, Herrmann, Eva, Edinger, Fabian, Koch, Christian, Kunzemann, Christian, Leicht, Dominik, Markmann, Melanie, Ruhrmann, Sophie, Schneck, Emanuel, Schulte, Dargmar, Gründling, Matthias, Brenig, Iris, Gerber, Manuela, Selleng, Kathleen, Wodrig, Sandra, Bloos, Frank, Bloos, Petra, Haucke, Anja, Knuhr-Kohlberg, Karina, Kolanos, Steffi, Schwope, Katrin, Thomas, Daniel, Buchholz, Corinna, Heller, Birte, Renner, Jochen, Schulz-Ruhtenberg, Nina, Elke, Gunnar, Fischer, Susanne, Hofbauer, Sabine, Straub, Peter, Zimmer, Sophie, Küllmar, Mira, Rosenow, Nadine, Massoth, Christina, Weiss, Raphael, Bitzinger, Diane, Pfister, Karin, Guzman, Ines, Kranke, Eva-Maria, Roewer, Norbert, Woeckel, Achim, Helmer, Philipp, and LIBERAL Collaboration Group

Subjects
Male, Time Factors, Medicine (miscellaneous), Clinical Trials, Phase IV as Topic, Red blood cell transfusion, surgery, Hemoglobins, Study Protocol, 0302 clinical medicine, Ischemia, Risk Factors, Cause of Death, Germany, Clinical endpoint, Multicenter Studies as Topic, Pharmacology (medical), Prospective Studies, 030212 general & internal medicine, Myocardial infarction, Stage (cooking), Randomized Controlled Trials as Topic, Aged, 80 and over, lcsh:R5-920, Age Factors, Acute kidney injury, Anemia, Treatment Outcome, Surgical Procedures, Operative, Female, Erythrocyte Transfusion, lcsh:Medicine (General), medicine.medical_specialty, elderly patients, Patient Readmission, Phase IV Trial, Perioperative Care, 03 medical and health sciences, Internal medicine, medicine, Humans, ddc:610, Adverse effect, Aged, anaemia, business.industry, Perioperative, medicine.disease, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Background Perioperative anaemia leads to impaired oxygen supply with a risk of vital organ ischaemia. In healthy and fit individuals, anaemia can be compensated by several mechanisms. Elderly patients, however, have less compensatory mechanisms because of multiple co-morbidities and age-related decline of functional reserves. The purpose of the study is to evaluate whether elderly surgical patients may benefit from a liberal red blood cell (RBC) transfusion strategy compared to a restrictive transfusion strategy. Methods The LIBERAL Trial is a prospective, randomized, multicentre, controlled clinical phase IV trial randomising 2470 elderly (≥ 70 years) patients undergoing intermediate- or high-risk non-cardiac surgery. Registered patients will be randomised only if Haemoglobin (Hb) reaches ≤9 g/dl during surgery or within 3 days after surgery either to the LIBERAL group (transfusion of a single RBC unit when Hb ≤ 9 g/dl with a target range for the post-transfusion Hb level of 9–10.5 g/dl) or the RESTRICTIVE group (transfusion of a single RBC unit when Hb ≤ 7.5 g/dl with a target range for the post-transfusion Hb level of 7.5–9 g/dl). The intervention per patient will be followed until hospital discharge or up to 30 days after surgery, whichever occurs first. The primary efficacy outcome is defined as a composite of all-cause mortality, acute myocardial infarction, acute ischaemic stroke, acute kidney injury (stage III), acute mesenteric ischaemia and acute peripheral vascular ischaemia within 90 days after surgery. Infections requiring iv antibiotics with re-hospitalisation are assessed as important secondary endpoint. The primary endpoint will be analysed by logistic regression adjusting for age, cancer surgery (y/n), type of surgery (intermediate- or high-risk), and incorporating centres as random effect. Discussion The LIBERAL-Trial will evaluate whether a liberal transfusion strategy reduces the occurrence of major adverse events after non-cardiac surgery in the geriatric population compared to a restrictive strategy within 90 days after surgery. Trial registration ClinicalTrials.gov (identifier: NCT03369210). Electronic supplementary material The online version of this article (10.1186/s13063-019-3200-3) contains supplementary material, which is available to authorized users.

Published
2019
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140. B

Author

Tanja Nadine, Stueber, Manfred, Wischnewsky, Elena, Leinert, Joachim, Diessner, Catharina, Bartmann, Roland Gregor, Stein, and Achim, Woeckel

Subjects
Adult, Aged, 80 and over, Lung Neoplasms, Brain Neoplasms, Receptor, ErbB-2, Clinical Decision-Making, Liver Neoplasms, Bone Neoplasms, Breast Neoplasms, Middle Aged, Prognosis, Survival Rate, Receptors, Estrogen, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Humans, Female, Neoplasm Recurrence, Local, Receptors, Progesterone, Aged, Follow-Up Studies, Retrospective Studies
Abstract

The BWe analyzed 641 metastasized patients, treated in 17 German certified breast cancer centers between 2001 and 2009. They were classified into low, intermediate, and high-risk groups according to BAccording to the BThis study demonstrates the reproducibility of the B

Published
2019

141. Umweltepidemiologische Grundlagen der Gesundheitswissenschaften

Author

Margarethe Woeckel, Regina Pickford, and Alexandra Schneider

Abstract

Die Umweltepidemiologie befasst sich mit der Wirkung von Umweltfaktoren auf physiologische Variablen und soziale Krankheitsfolgen in der Bevolkerung. Einleitend definiert der Beitrag essenzielle Variablen epidemiologischer Studien und Studienpopulationen. Verschiedene Studientypen, die je nach Untersuchungsziel zur Anwendung kommen, und sich in ihrer Art und Aussagefahigkeit unterscheiden, werden erlautert, z. B. Kohortenstudien, Fall-Kontroll-Studien und Querschnittstudien. Mit einem Schwerpunkt auf der Exposition gegenuber Luftschadstoffen werden Moglichkeiten zur Messung von Exposition, Gesundheitsendpunkten oder Zielgrosen und Confoundern vorgestellt. Schlieslich werden verschiedene Kriterien definiert, mittels derer die Qualitat der Untersuchungen gepruft werden kann. Dabei werden Aspekte der Kausalitat thematisiert sowie Hinweise zur Interpretation umweltepidemiologischer Studien und zu den Grenzen der Umweltepidemiologie gegeben.

Published
2019
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143. Implementation of a Systematic Literature Search Strategy in a National Breast Cancer Guideline: The Relevance of Systemic Therapy in Lymph Node Recurrent Disease

Author

Wolfgang Janni, Achim Woeckel, Stephanie Stangl, Wilfried Budach, Andreas D. Hartkopf, Christian Jackisch, Tanja Nadine Stueber, Michael P. Lux, Bernd Gerber, and Sara Y. Brucker

Subjects
Cancer Research, medicine.medical_specialty, Consensus, Antineoplastic Agents, Breast Neoplasms, 030230 surgery, Medical Oncology, Systemic therapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Randomized controlled trial, law, Medizinische Fakultät, Germany, Medicine, Humans, Medical physics, ddc:610, Disease management (health), Mastectomy, Randomized Controlled Trials as Topic, business.industry, Hematology, Evidence-based medicine, Guideline, medicine.disease, Observational Studies as Topic, Review Literature as Topic, Systematic review, Oncology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Practice Guidelines as Topic, Observational study, Female, Radiotherapy, Adjuvant, Lymph Nodes, Neoplasm Recurrence, Local, business
Abstract

Purpose:Our aim was to implement a structured literature search using PICO (patient/intervention/comparison/outcome) questions and a standardized consensus method for the German Guideline ‘Detection, diagnostics, therapy and follow-up of Breast Cancer' using, as an example, the significance of systemic therapy in lymph node recurrent disease (LNRD). Methods: We defined specified PICO questions according to the clinical significance of a recommendation for systemic therapies in locoregional LNRD. A methodologist performed a systematic literature search including randomized controlled trials, systematic reviews and observational studies (2007-2016). In a consensus conference, the level of evidence and consensus was determined and the clinical recommendation was adopted. Results: In total 143 publications were identified according to the search strategy including 14 duplicates, which were excluded. 4 publications were included based on experts' choice. The team excluded 119 publications, leaving 14 that were then screened by a full text search. Finally, 1 publication was found to be of methodologically and clinically reliable content. The conclusion of this publication in favor of systemic therapy for LNRD received strong consent from the consensus conference. Conclusions: The literature search strategy using PICO questions helped to achieve a fast and standardized selection of publications. The recommendation concerning systemic treatment of LNRD was first implemented in the update of the German Breast Cancer guideline.

Published
2018

145. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019

Author

Ditsch, Nina, Untch, Michael, Thill, Marc, Mueller, Volkmar, Janni, Wolfgang, Albert, Ute-Susann, Bauerfeind, Ingo, Blohmer, Jens, Budach, Wilfried, Dall, Peter, Diel, Ingo, Fasching, Peter A., Fehm, Tanja, Friedrich, Michael, Gerber, Bernd, Hanf, Volker, Harbeck, Nadia, Huober, Jens, Jackisch, Christian, Kolberg-Liedtke, Cornelia, Kreipe, Hans-Heinrich, Krug, David, Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael Patrick, Maass, Nicolai, Moebus, Volker, Mueller-Schimpfle, Markus, Mundhenke, Christoph, Nitz, Ulrike, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schuetz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Wenz, Frederik, Witzel, Isabell, Woeckel, Achim, Ditsch, Nina, Untch, Michael, Thill, Marc, Mueller, Volkmar, Janni, Wolfgang, Albert, Ute-Susann, Bauerfeind, Ingo, Blohmer, Jens, Budach, Wilfried, Dall, Peter, Diel, Ingo, Fasching, Peter A., Fehm, Tanja, Friedrich, Michael, Gerber, Bernd, Hanf, Volker, Harbeck, Nadia, Huober, Jens, Jackisch, Christian, Kolberg-Liedtke, Cornelia, Kreipe, Hans-Heinrich, Krug, David, Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael Patrick, Maass, Nicolai, Moebus, Volker, Mueller-Schimpfle, Markus, Mundhenke, Christoph, Nitz, Ulrike, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schuetz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Wenz, Frederik, Witzel, Isabell, and Woeckel, Achim

Published
2019

146. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2019

Author

Thill, Marc, Jackisch, Christian, Janni, Wolfgang, Mueller, Volkmar, Albert, Ute-Susann, Bauerfeind, Ingo, Blohmer, Jens, Budach, Wilfried, Dall, Peter, Diel, Ingo, Fasching, Peter A., Fehm, Tanja, Friedrich, Michael, Gerber, Bernd, Hanf, Volker, Harbeck, Nadia, Huober, Jens, Kolberg-Liedtke, Cornelia, Kreipe, Hans-Heinrich, Krug, David, Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael Patrick, Maass, Nicolai, Moebus, Volker, Mueller-Schimpfle, Markus, Mundhenke, Christoph, Nitz, Ulrike, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schuetz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Wenz, Frederik, Witzel, Isabell, Woeckel, Achim, Ditsch, Nina, Thill, Marc, Jackisch, Christian, Janni, Wolfgang, Mueller, Volkmar, Albert, Ute-Susann, Bauerfeind, Ingo, Blohmer, Jens, Budach, Wilfried, Dall, Peter, Diel, Ingo, Fasching, Peter A., Fehm, Tanja, Friedrich, Michael, Gerber, Bernd, Hanf, Volker, Harbeck, Nadia, Huober, Jens, Kolberg-Liedtke, Cornelia, Kreipe, Hans-Heinrich, Krug, David, Kuehn, Thorsten, Kuemmel, Sherko, Loibl, Sibylle, Lueftner, Diana, Lux, Michael Patrick, Maass, Nicolai, Moebus, Volker, Mueller-Schimpfle, Markus, Mundhenke, Christoph, Nitz, Ulrike, Rhiem, Kerstin, Rody, Achim, Schmidt, Marcus, Schneeweiss, Andreas, Schuetz, Florian, Sinn, Hans-Peter, Solbach, Christine, Solomayer, Erich-Franz, Stickeler, Elmar, Thomssen, Christoph, Untch, Michael, Wenz, Frederik, Witzel, Isabell, Woeckel, Achim, and Ditsch, Nina

Abstract

Every year the Breast Committee of the Arbeitsgemeinschaft Gynakologische Onkologie (German Gynecological Oncology Group, AGO), a group of gynecological oncologists specialized in breast cancer and interdisciplinary members specialized in pathology, radiologic diagnostics, medical oncology, and radiation oncology, prepares and updates evidence-based recommendations for the diagnosis and treatment of patients with early and metastatic breast cancer. Every update is performed according to a documented rule-fixed algorithm, by thoroughly reviewing and scoring the recent publications for their scientific validity and clinical relevance. This current publication presents the 2019 update on the recommendations for metastatic breast cancer.

Published
2019

147. High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer

Author

Bick, Ulrich, Engel, Christoph, Krug, Barbara, Heindel, Walter, Fallenberg, Eva M., Rhiem, Kerstin, Maintz, David, Golatta, Michael, Speiser, Dorothee, Rjosk-Dendorfer, Dorothea, Laemmer-Skarke, Irina, Dietzel, Frederic, Schaefer, Karl Werner Fritz, Leinert, Elena, Weigel, Stefanie, Sauer, Stephanie, Pertschy, Stefanie, Hofmockel, Thomas, Hagert-Winkler, Anne, Kast, Karin, Quante, Anne, Meindl, Alfons, Kiechle, Marion, Loeffler, Markus, Schmutzler, Rita K., Blohmer, Jens-Uwe, Horn, Denise, Varon-Mateeva, Raymonda, Huebbel, Verena, Herold, Natalie, Puesken, Michael, Wimberger, Pauline, Meisel, Cornelia, Keller, Katja, Antoch, Gerald, Vesper, Anne-Sophie, Fehm, Tanja N., Schlegelberger, Brigitte, Auber, Bernd, Wallaschek, Hannah, Heil, Joerg, Schott, Sarah, Dikow, Nicola, Mundhenke, Christoph, Arnold, Norbert, Caliebe, Almuth, Briest, Susanne, Lemke, Johannes, Gril, Sabine, Pfeifer, Katharina, Ramser, Juliane, Mahner, Sven, Ditsch, Nina, Zeder-Goess, Christine, Tio, Joke, Burg, Matthias, Horvath, Judith, Siebert, Reiner, Bartholomae, Jasmin, Janni, Wolfgang, Bley, Thorsten, Woeckel, Achim, Haaf, Thomas, Zachariae, Silke, Bucksch, Karolin, Enders, Ute, Bick, Ulrich, Engel, Christoph, Krug, Barbara, Heindel, Walter, Fallenberg, Eva M., Rhiem, Kerstin, Maintz, David, Golatta, Michael, Speiser, Dorothee, Rjosk-Dendorfer, Dorothea, Laemmer-Skarke, Irina, Dietzel, Frederic, Schaefer, Karl Werner Fritz, Leinert, Elena, Weigel, Stefanie, Sauer, Stephanie, Pertschy, Stefanie, Hofmockel, Thomas, Hagert-Winkler, Anne, Kast, Karin, Quante, Anne, Meindl, Alfons, Kiechle, Marion, Loeffler, Markus, Schmutzler, Rita K., Blohmer, Jens-Uwe, Horn, Denise, Varon-Mateeva, Raymonda, Huebbel, Verena, Herold, Natalie, Puesken, Michael, Wimberger, Pauline, Meisel, Cornelia, Keller, Katja, Antoch, Gerald, Vesper, Anne-Sophie, Fehm, Tanja N., Schlegelberger, Brigitte, Auber, Bernd, Wallaschek, Hannah, Heil, Joerg, Schott, Sarah, Dikow, Nicola, Mundhenke, Christoph, Arnold, Norbert, Caliebe, Almuth, Briest, Susanne, Lemke, Johannes, Gril, Sabine, Pfeifer, Katharina, Ramser, Juliane, Mahner, Sven, Ditsch, Nina, Zeder-Goess, Christine, Tio, Joke, Burg, Matthias, Horvath, Judith, Siebert, Reiner, Bartholomae, Jasmin, Janni, Wolfgang, Bley, Thorsten, Woeckel, Achim, Haaf, Thomas, Zachariae, Silke, Bucksch, Karolin, and Enders, Ute

Abstract

Purpose To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Methods A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. Results A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5 (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9 parts per thousand (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. Conclusions High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Published
2019

148. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., Spurdle, Amanda B., Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., and Spurdle, Amanda B.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

149. Mindfulness-based stress reduction for women diagnosed with breast cancer

Author

Schell, Lisa K., Monsef, Ina, Woeckel, Achim, Skoetz, Nicole, Schell, Lisa K., Monsef, Ina, Woeckel, Achim, and Skoetz, Nicole

Abstract

Background Breast cancer is the most common cancer in women. Diagnosis and treatment may drastically affect quality of life, causing symptoms such as sleep disorders, depression and anxiety. Mindfulness-based stress reduction (MBSR) is a programme that aims to reduce stress by developing mindfulness, meaning a non-judgmental, accepting moment-by-moment awareness. MBSR seems to benefit patients with mood disorders and chronic pain, and it may also benefit women with breast cancer. Objectives To assess the effects of mindfulness-based stress reduction (MBSR) in women diagnosed with breast cancer. Search methods In April 2018, we conducted a comprehensive electronic search for studies of MBSR in women with breast cancer, in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trial registries (World Health Organization's International Clinical Trials Registry Platform WHO ICTRP) and ClinicalTrials.gov ). We also handsearched relevant conference proceedings. Selection criteria Randomised clinical trials (RCTs) comparing MBSR versus no intervention in women with breast cancer. Data collection and analysis We used standard methodological procedures expected by Cochrane. Using a standardised data form, the review authors extracted data in duplicate on methodological quality, participants, interventions and outcomes of interest (quality of life, fatigue, depression, anxiety, quality of sleep, overall survival and adverse events). For outcomes assessed with the same instrument, we used the mean difference (MD) as a summary statistic for meta-analysis; for those assessed with different instruments, we used the standardised mean difference (SMD). The effect of MBSR was assessed in the short term (end of intervention), medium term (up to 6 months after intervention) and long term (up to 24 months after intervention). Main results Fourteen RCTs fulfilled our inclusion criteria, with most studies reporting that they included women with early brea

Published
2019

150. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, MT, Tudini, E, Li, H, Hahnen, E, Wappenschmidt, B, Feliubadalo, L, Aalfs, CM, Agata, S, Aittomaki, K, Alducci, E, Concepcion Alonso-Cerezo, M, Arnold, N, Auber, B, Austin, R, Azzollini, J, Balmana, J, Barbieri, E, Bartram, CR, Blanco, A, Bluemcke, B, Bonache, S, Bonanni, B, Borg, A, Bortesi, B, Brunet, J, Bruzzone, C, Bucksch, K, Cagnoli, G, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Capone, GL, Caputo, SM, Carnevali, I, Carrasco, E, Caux-Moncoutier, V, Cavalli, P, Cini, G, Clarke, EM, Concolino, P, Cops, EJ, Cortesi, L, Couch, FJ, Darder, E, de la Hoya, M, Dean, M, Debatin, I, Del Valle, J, Delnatte, C, Derive, N, Diez, O, Ditsch, N, Domchek, SM, Dutrannoy, V, Eccles, DM, Ehrencrona, H, Enders, U, Evans, DG, Farra, C, Faust, U, Felbor, U, Feroce, I, Fine, M, Foulkes, WD, Galvao, HC, Gambino, G, Gehrig, A, Gensini, F, Gerdes, A-M, Germani, A, Giesecke, J, Gismondi, V, Gomez, C, Garcia, EBG, Gonzalez, S, Grau, E, Grill, S, Gross, E, Guerrieri-Gonzaga, A, Guillaud-Bataille, M, Gutierrez-Enriquez, S, Haaf, T, Hackmann, K, Hansen, TV, Harris, M, Hauke, J, Heinrich, T, Hellebrand, H, Herold, KN, Honisch, E, Horvath, J, Houdayer, C, Huebbel, V, Iglesias, S, Izquierdo, A, James, PA, Janssen, LA, Jeschke, U, Kaulfuss, S, Keupp, K, Kiechle, M, Koelbl, A, Krieger, S, Kruse, TA, Kvist, A, Lalloo, F, Larsen, M, Lattimore, VL, Lautrup, C, Ledig, S, Leinert, E, Lewis, AL, Lim, J, Loeffler, M, Lopez-Fernandez, A, Lucci-Cordisco, E, Maass, N, Manoukian, S, Marabelli, M, Matricardi, L, Meindl, A, Michelli, RD, Moghadasi, S, Moles-Fernandez, A, Montagna, M, Montalban, G, Monteiro, AN, Montes, E, Mori, L, Moserle, L, Mueller, CR, Mundhenke, C, Naldi, N, Nathanson, KL, Navarro, M, Nevanlinna, H, Nichols, CB, Niederacher, D, Nielsen, HR, Ong, K-R, Pachter, N, Palmero, E, Papi, L, Pedersen, IS, Peissel, B, Perez-Segura, P, Pfeifer, K, Pineda, M, Pohl-Rescigno, E, Poplawski, NK, Porfirio, B, Quante, AS, Ramser, J, Reis, RM, Revillion, F, Rhiem, K, Riboli, B, Ritter, J, Rivera, D, Rofes, P, Rump, A, Salinas, M, Sanchez de Abajo, AM, Schmidt, G, Schoenwiese, U, Seggewiss, J, Solanes, A, Steinemann, D, Stiller, M, Stoppa-Lyonnet, D, Sullivan, KJ, Susman, R, Sutter, C, Tavtigian, S, Teo, SH, Teule, A, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tornero, E, Torngren, T, Torres-Esquius, S, Toss, A, Trainer, AH, Tucker, KM, van Asperen, CJ, van Mackelenbergh, MT, Varesco, L, Vargas-Parra, G, Varon, R, Vega, A, Velasco, A, Vesper, A-S, Viel, A, Vreeswijk, MPG, Wagner, SA, Waha, A, Walker, LC, Walters, RJ, Wang-Gohrke, S, Weber, BHF, Weichert, W, Wieland, K, Wiesmueller, L, Witzel, I, Woeckel, A, Woodward, ER, Zachariae, S, Zampiga, V, Zeder-Goss, C, Lazaro, C, De Nicolo, A, Radice, P, Engel, C, Schmutzler, RK, Goldgar, DE, Spurdle, AB, Parsons, MT, Tudini, E, Li, H, Hahnen, E, Wappenschmidt, B, Feliubadalo, L, Aalfs, CM, Agata, S, Aittomaki, K, Alducci, E, Concepcion Alonso-Cerezo, M, Arnold, N, Auber, B, Austin, R, Azzollini, J, Balmana, J, Barbieri, E, Bartram, CR, Blanco, A, Bluemcke, B, Bonache, S, Bonanni, B, Borg, A, Bortesi, B, Brunet, J, Bruzzone, C, Bucksch, K, Cagnoli, G, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Capone, GL, Caputo, SM, Carnevali, I, Carrasco, E, Caux-Moncoutier, V, Cavalli, P, Cini, G, Clarke, EM, Concolino, P, Cops, EJ, Cortesi, L, Couch, FJ, Darder, E, de la Hoya, M, Dean, M, Debatin, I, Del Valle, J, Delnatte, C, Derive, N, Diez, O, Ditsch, N, Domchek, SM, Dutrannoy, V, Eccles, DM, Ehrencrona, H, Enders, U, Evans, DG, Farra, C, Faust, U, Felbor, U, Feroce, I, Fine, M, Foulkes, WD, Galvao, HC, Gambino, G, Gehrig, A, Gensini, F, Gerdes, A-M, Germani, A, Giesecke, J, Gismondi, V, Gomez, C, Garcia, EBG, Gonzalez, S, Grau, E, Grill, S, Gross, E, Guerrieri-Gonzaga, A, Guillaud-Bataille, M, Gutierrez-Enriquez, S, Haaf, T, Hackmann, K, Hansen, TV, Harris, M, Hauke, J, Heinrich, T, Hellebrand, H, Herold, KN, Honisch, E, Horvath, J, Houdayer, C, Huebbel, V, Iglesias, S, Izquierdo, A, James, PA, Janssen, LA, Jeschke, U, Kaulfuss, S, Keupp, K, Kiechle, M, Koelbl, A, Krieger, S, Kruse, TA, Kvist, A, Lalloo, F, Larsen, M, Lattimore, VL, Lautrup, C, Ledig, S, Leinert, E, Lewis, AL, Lim, J, Loeffler, M, Lopez-Fernandez, A, Lucci-Cordisco, E, Maass, N, Manoukian, S, Marabelli, M, Matricardi, L, Meindl, A, Michelli, RD, Moghadasi, S, Moles-Fernandez, A, Montagna, M, Montalban, G, Monteiro, AN, Montes, E, Mori, L, Moserle, L, Mueller, CR, Mundhenke, C, Naldi, N, Nathanson, KL, Navarro, M, Nevanlinna, H, Nichols, CB, Niederacher, D, Nielsen, HR, Ong, K-R, Pachter, N, Palmero, E, Papi, L, Pedersen, IS, Peissel, B, Perez-Segura, P, Pfeifer, K, Pineda, M, Pohl-Rescigno, E, Poplawski, NK, Porfirio, B, Quante, AS, Ramser, J, Reis, RM, Revillion, F, Rhiem, K, Riboli, B, Ritter, J, Rivera, D, Rofes, P, Rump, A, Salinas, M, Sanchez de Abajo, AM, Schmidt, G, Schoenwiese, U, Seggewiss, J, Solanes, A, Steinemann, D, Stiller, M, Stoppa-Lyonnet, D, Sullivan, KJ, Susman, R, Sutter, C, Tavtigian, S, Teo, SH, Teule, A, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tornero, E, Torngren, T, Torres-Esquius, S, Toss, A, Trainer, AH, Tucker, KM, van Asperen, CJ, van Mackelenbergh, MT, Varesco, L, Vargas-Parra, G, Varon, R, Vega, A, Velasco, A, Vesper, A-S, Viel, A, Vreeswijk, MPG, Wagner, SA, Waha, A, Walker, LC, Walters, RJ, Wang-Gohrke, S, Weber, BHF, Weichert, W, Wieland, K, Wiesmueller, L, Witzel, I, Woeckel, A, Woodward, ER, Zachariae, S, Zampiga, V, Zeder-Goss, C, Lazaro, C, De Nicolo, A, Radice, P, Engel, C, Schmutzler, RK, Goldgar, DE, and Spurdle, AB

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

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