1.

Breast Cancer Res Treat. 2019 Jul;176(2):481-482. doi: 10.1007/s10549-019-05287-9.

Correction to: Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

Rageth CJ^1,2, O'Flynn EAM³, Pinker K⁴, Kubik-Huch RA⁵, Mundinger A⁶, Decker T⁷, Tausch C⁸, Dammann F⁹, Baltzer PA¹⁰, Fallenberg EM¹¹, Foschini MP¹², Dellas S¹³, Knauer M¹⁴, Malhaire C¹⁵, Sonnenschein M¹⁶, Boos A¹⁷, Morris E⁴, Varga Z¹⁸.

Author information:
1. Département de Gynécologie et d'Obstétrique, Centre du sein, Hôpitaux Universitaires de Genève, Bd de la Cluse 30, 1211, Geneva 14, Switzerland. jcr@2cr.ch.
2. , Ringlikerstrasse 53, 8142, Uitikon Waldegg, Switzerland. jcr@2cr.ch.
3. The Rose Centre, St George's University Hospitals NHS Foundation Trust, Perimeter Road, London, SW17 0QT, UK.
4. Breast Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 300 E 66th St, New York, NY, 10065, USA.
5. Department of Medical Services, Institute of Radiology, Kantonsspital Baden, im Ergel, 5404, Baden, Switzerland.
6. Zentrum Radiologie der Niels-Stensen-Kliniken; Marienhospital Osnabrück, Bischofsstraße 1, 49074, Osnabrück, Germany.
7. Institut für Pathologie am Dietrich-Bonhoeffer-Klinikum, Salvador-Allende-Straße 30, 17036, Neubrandenburg, Germany.
8. Brust-Zentrum Zürich, Seefeldstr. 214, 8008, Zurich, Switzerland.
9. Interventional and Pediatric Radiology, Department of Diagnostic, Inselspital, University Hospital Bern, Freiburgstrasse 10, 3010, Bern, Switzerland.
10. Department of Biomedical Imaging and Image-guided Therapy, Allgemeines Krankenhaus, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
11. Department of Radiology, University Hospital, Ludwig Maximilian University Munich, Marchioninistr. 15, 81377, Munich, Germany.
12. Department of Biomedical and Neuromotor Sciences, Unit of Anatomic Pathology at Bellaria Hospital, University of Bologna, Via Altura 3, 40139, Bologna, Italy.
13. Clinic of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.
14. Breast Center St. Gallen, Cantonal Hospital St. Gallen, Rorschacher Str. 95, 9007, St. Gallen, Switzerland.
15. Imaging Department, Institut Curie, PSL Research University, Paris, France.
16. Division of Radiology, Breast Center Bern (Brustzentrum Bern), Klinik Engeried, Lindenhofgruppe AG, Riedweg 15, 3012, Bern, Switzerland.
17. Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
18. Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland Schmelzbergstrasse 12., 8091, Zurich, Switzerland.

Erratum for

• Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions). [Breast Cancer Res Treat. 2019]

Abstract

The article Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions), written by Christoph J Rageth, Elizabeth AM O'Flynn, Katja Pinker, Rahel A Kubik-Huch, Alexander Mundinger, Thomas Decker, Christoph Tausch, Florian Dammann, Pascal A. Baltzer, Eva Maria Fallenberg, Maria P Foschini, Sophie Dellas, Michael Knauer, Caroline Malhaire, Martin Sonnenschein, Andreas Boos, Elisabeth Morris, Zsuzsanna Varga, was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 30, 2018 without open access.

PMCID: PMC6555776 Free PMC Article

PMID: 31152325

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2.

Ann Surg. 2019 Jun;269(6):1163-1169. doi: 10.1097/SLA.0000000000002771.

Impact of Breast Surgery in Primary Metastasized Breast Cancer: Outcomes of the Prospective Randomized Phase III ABCSG-28 POSYTIVE Trial.

Fitzal F¹, Bjelic-Radisic V², Knauer M³, Steger G^4,5, Hubalek M⁶, Balic M⁷, Singer C⁸, Bartsch R⁹, Schrenk P¹⁰, Soelkner L¹¹, Greil R¹², Gnant M¹; ABCSG.

Author information:
1. Department of Surgery, Medical University, Vienna, Austria.
2. Department of Gynecology, Medical University, Graz, Austria.
3. Breast Health Center, St Gallen, Austria.
4. Medical Oncology, Medical University, Vienna, Austria.
5. Gaston H. Glock Research Center, Medical University, Vienna, Austria.
6. Department of Gynecology, Breast Health Center Hall, Tirol, Austria.
7. Medical Oncology, Medical University, Graz, Austria.
8. Gynecology, Medical University, Graz, Austria.
9. German Breast Group, Breast Health Center Hall, Tirol, Austria.
10. Department of Surgery, Medical University, Linz, Austria.
11. Austrian Breast and Colorectal Cancer Study Group, Medical University, Linz, Austria.
12. Department of Medical Oncology, Paracelsus Medical University, Salzburg, Austria.

Abstract

BACKGROUND:

Conflicting evidence exists regarding the value of surgical resection of the primary in stage IV breast cancer patients.

OBJECTIVE:

The prospective randomized phase III ABCSG-28 POSYTIVE trial evaluated median survival comparing primary surgery followed by systemic therapy to primary systemic therapy in de novo stage IV breast cancer.

METHODS:

Between 2011 and 2015, 90 previously untreated stage IV breast cancer patients were randomly assigned to surgical resection of the primary tumor followed by systemic therapy (Arm A) or primary systemic therapy (Arm B) in Austria. Overall survival (OS) was defined as the primary study endpoint.

RESULTS:

The trial was stopped early due to poor recruitment. Ninety patients (45 arm A, 45 arm B) were included; median follow-up was 37.5 months. Patients in the surgery arm had more cT3 breast cancer (22.2% vs 6.7%) and more cN2 staging (15.6% vs 4.4%). Both groups were well balanced with respect to the type of first-line systemic treatment. Median survival in arm A was 34.6 months, versus 54.8 months in the nonsurgery arm [hazard ratio (HR) 0.691, 95% confidence interval (95% CI) 0.358-1.333; P = 0.267]; time to distant progression was 13.9 months in the surgery arm and 29.0 months in the nonsurgery arm (HR 0.598, 95% CI 0.343-1.043; P = 0.0668).

CONCLUSION:

The prospective phase III trial ABCSG-28 (POSYTIVE) could not demonstrate an OS benefit for surgical resection of the primary in breast cancer patients presenting with de novo stage IV disease.

PMID: 31082916

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3.

Breast Cancer Res Treat. 2019 Jun;175(2):389-399. doi: 10.1007/s10549-018-05075-x. Epub 2019 Feb 22.

Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study.

Wuerstlein R^1,2, Kates R³, Gluz O^3,4,5, Grischke EM⁶, Schem C⁷, Thill M⁸, Hasmueller S⁹, Köhler A¹⁰, Otremba B¹¹, Griesinger F¹², Schindlbeck C¹³, Trojan A¹⁴, Otto F¹⁵, Knauer M¹⁶, Pusch R¹⁷, Harbeck N^18,3; WSG-PRIMe investigators in Germany, Austria, Switzerland.

Collaborators: (26)

Grischke EM, Harbeck N, Schem C, Gluz O, Thill M, Hasmüller S, Köhler A, Otremba B, Griesinger F, Schindlbeck C, Reimer T, Krauter J, Tomé O, Friedrichs K, Albert US, Gebauer G, Ackermann S, Scheffen I, Kaltenecker G, Overkamp F, Schrader I, Potenberg J, Enzinger HM, Trojan A, Otto F, Pusch R.

Author information:
1. Department of Gynecology and Obstetrics, Breast Center, University of Munich (LMU), CCC Munich, Munich, Germany. rachel.wuerstlein@med.uni-muenchen.de.
2. West German Study Group GmbH, Moenchengladbach, Germany. rachel.wuerstlein@med.uni-muenchen.de.
3. West German Study Group GmbH, Moenchengladbach, Germany.
4. Brustzentrum Niederrhein, Evangelisches Krankenhaus Bethesda, Mönchengladbach, Germany.
5. University Hospital Cologne, Cologne, Germany.
6. Universitätsfrauenklinik Tuebingen, Tuebingen, Germany.
7. Universitätsklinikum Kiel, Frauenklinik, Kiel, Germany.
8. Agaplesion Markus Hospital, Frankfurt, Germany.
9. Ebersberg Clinic, Ebersberg, Germany.
10. Gemeinschaftspraxis für Hämatologie und Onkologie, Langen, Germany.
11. Onkologische Praxis Oldenburg, Oldenburg, Germany.
12. Klinikzentrum für Hämatologie und Onkologie, Oldenburg, Germany.
13. Klinikum Traunstein, Frauenklinik, Traunstein, Germany.
14. Brust-Zentrum Zürich, Zurich, Switzerland.
15. Tumor-und Brustzentrum ZeTuP and Brustzentrum Stephanshorn, St. Gallen, Switzerland.
16. Breast Center Kantonsspital St. Gallen, St. Gallen, Switzerland.
17. Ordensklinikum Linz, Linz, Austria.
18. Department of Gynecology and Obstetrics, Breast Center, University of Munich (LMU), CCC Munich, Munich, Germany.

Abstract

PURPOSE:

The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer.

METHODS:

452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therapy recommendations based on clinicopathological factors. After prospective risk classification by MammaPrint/BluePrint was revealed, post-test treatment recommendations and actual treatment were recorded. Decisional Conflict and anxiety were measured by questionnaires.

RESULTS:

Post-test switch (in chemotherapy (CT) recommendation) occurred in 29.1% of cases. Overall, physician adherence to MP risk assessment was 92.3% for low-risk and 94.3% for high-risk MP scores. Adherence was remarkably high in "discordant" groups: 74.7% of physicians initially recommending CT switched to CT omission following low-risk MP scores; conversely, 88.9% of physicians initially recommending CT omission switched to CT recommendations following high-risk MP scores. Most patients (99.2%) recommended to forgo CT post-test and 21.3% of patients with post-test CT recommendations did not undergo CT; among MP low-risk patients with pre-test and post-test CT recommendations, 40% did not actually undergo CT. Luminal subtype assessment by BluePrint was discordant with IHC assessment in 34% of patients. Patients' State Anxiety scores improved significantly overall, particularly in MP low-risk patients. Trait Anxiety scores increased slightly in MP high risk and decreased slightly in MP low-risk patients.

CONCLUSIONS:

MammaPrint and BluePrint test results strongly impacted physicians' therapy decisions in luminal EBC with up to three involved lymph nodes. The high adherence to genetically determined risk assessment represents a key prerequisite for achieving a personalized cost-effective approach to disease management of early breast cancer.

PMCID: PMC6533223 Free PMC Article

PMID: 30796651

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4.

Breast Cancer Res Treat. 2019 Apr;174(2):279-296. doi: 10.1007/s10549-018-05071-1. Epub 2018 Nov 30.

Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions).

Rageth CJ^1,2, O'Flynn EAM³, Pinker K⁴, Kubik-Huch RA⁵, Mundinger A⁶, Decker T⁷, Tausch C⁸, Dammann F⁹, Baltzer PA¹⁰, Fallenberg EM¹¹, Foschini MP¹², Dellas S¹³, Knauer M¹⁴, Malhaire C¹⁵, Sonnenschein M¹⁶, Boos A¹⁷, Morris E⁴, Varga Z¹⁸.

Author information:
1. Département de Gynécologie et d'Obstétrique, Centre du sein, Hôpitaux Universitaires de Genève, Bd de la Cluse 30, 1211, Geneva 14, Switzerland. jcr@2cr.ch.
2. , Ringlikerstrasse 53, 8142, Uitikon Waldegg, Switzerland. jcr@2cr.ch.
3. The Rose Centre, St George's University Hospitals NHS Foundation Trust, Perimeter Road, London, SW17 0QT, UK.
4. Breast Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, 300 E 66th St, New York, NY, 10065, USA.
5. Department of Medical Services, Institute of Radiology, Kantonsspital Baden, im Ergel, 5404, Baden, Switzerland.
6. Zentrum Radiologie der Niels-Stensen-Kliniken; Marienhospital Osnabrück, Bischofsstraße 1, 49074, Osnabrück, Germany.
7. Institut für Pathologie am Dietrich-Bonhoeffer-Klinikum, Salvador-Allende-Straße 30, 17036, Neubrandenburg, Germany.
8. Brust-Zentrum Zürich, Seefeldstr. 214, 8008, Zurich, Switzerland.
9. Interventional and Pediatric Radiology, Department of Diagnostic, Inselspital, University Hospital Bern, Freiburgstrasse 10, 3010, Bern, Switzerland.
10. Department of Biomedical Imaging and Image-guided Therapy, Allgemeines Krankenhaus, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
11. Department of Radiology, University Hospital, Ludwig Maximilian University Munich, Marchioninistr. 15, 81377, Munich, Germany.
12. Department of Biomedical and Neuromotor Sciences, Unit of Anatomic Pathology at Bellaria Hospital, University of Bologna, Via Altura 3, 40139, Bologna, Italy.
13. Clinic of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.
14. Breast Center St. Gallen, Cantonal Hospital St. Gallen, Rorschacher Str. 95, 9007, St. Gallen, Switzerland.
15. Imaging Department, Institut Curie, PSL Research University, Paris, France.
16. Division of Radiology, Breast Center Bern (Brustzentrum Bern), Klinik Engeried, Lindenhofgruppe AG, Riedweg 15, 3012, Bern, Switzerland.
17. Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistr. 100, 8091, Zurich, Switzerland.
18. Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland Schmelzbergstrasse 12., 8091, Zurich, Switzerland.

Erratum in

• Correction to: Second International Consensus Conference on lesions of uncertain malignant potential in the breast (B3 lesions). [Breast Cancer Res Treat. 2019]

Abstract

PURPOSE:

The second International Consensus Conference on B3 lesions was held in Zurich, Switzerland, in March 2018, organized by the International Breast Ultrasound School to re-evaluate the consensus recommendations.

METHODS:

This study (1) evaluated how management recommendations of the first Zurich Consensus Conference of 2016 on B3 lesions had influenced daily practice and (2) reviewed current literature towards recommendations to biopsy.

RESULTS:

In 2018, the consensus recommendations for management of B3 lesions remained almost unchanged: For flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL) and radial scars (RS) diagnosed on core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB), excision by VAB in preference to open surgery, and for atypical ductal hyperplasia (ADH) and phyllodes tumors (PT) diagnosed at VAB or CNB, first-line open surgical excision (OE) with follow-up surveillance imaging for 5 years. Analyzing the Database of the Swiss Minimally Invasive Breast Biopsies (MIBB) with more than 30,000 procedures recorded, there was a significant increase in recommending more frequent surveillance of LN [65% in 2018 vs. 51% in 2016 (p = 0.004)], FEA (72% in 2018 vs. 62% in 2016 (p = 0.005)), and PL [(76% in 2018 vs. 70% in 2016 (p = 0.04)] diagnosed on VAB. A trend to more frequent surveillance was also noted also for RS [77% in 2018 vs. 67% in 2016 (p = 0.07)].

CONCLUSIONS:

Minimally invasive management of B3 lesions (except ADH and PT) with VAB continues to be appropriate as an alternative to first-line OE in most cases, but with more frequent surveillance, especially for LN.

PMCID: PMC6538569 Free PMC Article

PMID: 30506111 [Indexed for MEDLINE]

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5.

Trials. 2018 Dec 4;19(1):667. doi: 10.1186/s13063-018-3021-9.

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial.

Henke G¹, Knauer M², Ribi K^3,4, Hayoz S³, Gérard MA³, Ruhstaller T², Zwahlen DR⁵, Muenst S^6,7, Ackerknecht M^8,7, Hawle H³, Fitzal F^9,10, Gnant M^9,10, Mátrai Z¹¹, Ballardini B¹², Gyr A^13,7, Kurzeder C^13,7, Weber WP^14,15.

Author information:
1. Department of Radiation Oncology, St. Gallen Cantonal Hospital, Rorschacher Strasse 95, 9007, St.Gallen, Switzerland.
2. Breast Center, St. Gallen Cantonal Hospital, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.
3. SAKK Coordinating Center, Effingerstrasse 33, 3008, Bern, Switzerland.
4. IBCSG Coordinating Center, Effingerstrasse 40, 3008, Bern, Switzerland.
5. Department of Radiation Oncology, Graubünden Cantonal Hospital, Loestrasse 170, 7000, Chur, Switzerland.
6. Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland.
7. Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056, Basel, Switzerland.
8. Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031, Basel, Switzerland.
9. Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
10. Breast Health Center, Comprehensive Cancer Center Vienna, Spitalgasse 23, 1090, Vienna, Austria.
11. Department of Breast and Sarcoma Surgery, National Institute of Oncology, Ráth György u. 7-9, 1122, Budapest, Hungary.
12. Breast Unit, Gruppo MultiMedica, Via Fantoli 16/15, Milan, 20138, Italy.
13. Breast Center, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
14. Breast Center, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland. walter.weber@usb.ch.
15. Faculty of Medicine, University of Basel, Klingelbergstrasse 61, 4056, Basel, Switzerland. walter.weber@usb.ch.

Abstract

BACKGROUND:

Complete lymph node removal through conventional axillary dissection (ALND) has been standard treatment for breast cancer patients for almost a century. In the 1990s, however, and in parallel with the advent of the sentinel lymph node (SLN) procedure, ALND came under increasing scrutiny due to its association with significant patient morbidity. Several studies have since provided evidence to suggest omission of ALND, often in favor of axillary radiation, in selected clinically node-negative, SLN-positive patients, thus supporting the current trend in clinical practice. Clinically node-positive patients, by contrast, continue to undergo ALND in many cases, if only for the lack of studies re-assessing the indication for ALND in these patients. Hence, there is a need for a clinical trial to evaluate the optimal treatment for clinically node-positive breast cancer patients in terms of surgery and radiotherapy. The TAXIS trial is designed to fill this gap by examining in particular the value of tailored axillary surgery (TAS), a new technique for selectively removing positive lymph nodes.

METHODS:

In this international, multicenter, phase-III, non-inferiority, randomized controlled trial (RCT), including 34 study sites from four different countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS followed by regional nodal irradiation including the full axilla. All patients undergo adjuvant whole-breast irradiation after breast-conserving surgery and chest-wall irradiation after mastectomy. The main objective of the trial is to test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival of clinically node-positive breast cancer patients in the era of effective systemic therapy and extended regional nodal irradiation. The trial was activated on 31 July 2018 and the first patient was randomized on 7 August 2018.

DISCUSSION:

Designed to test the hypothesis that TAS is non-inferior to ALND in terms of curing patients and preventing recurrences, yet is significantly superior in reducing patient morbidity, this trial may establish a new worldwide treatment standard in breast cancer surgery. If found to be non-inferior to standard treatment, TAS may significantly contribute to reduce morbidity in breast cancer patients by avoiding surgical overtreatment.

TRIAL REGISTRATION:

ClinicalTrials.gov, ID: NCT03513614. Registered on 1 May 2018. www.kofam.ch , ID: NCT03513614 . Registered on 17 June 2018. EudraCT No.: 2018-000372-14.

PMCID: PMC6278139 Free PMC Article

PMID: 30514362 [Indexed for MEDLINE]

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6.

Eur J Surg Oncol. 2019 Apr;45(4):538-543. doi: 10.1016/j.ejso.2018.10.001. Epub 2018 Oct 10.

The influence of breast cancer subtypes on axillary ultrasound accuracy: A retrospective single center analysis of 583 women.

Helfgott R¹, Mittlböck M², Miesbauer M³, Moinfar F⁴, Haim S⁵, Mascherbauer M⁶, Schlagnitweit P⁶, Heck D⁶, Knauer M⁷, Fitzal F⁸.

Author information:
1. Sisters of Charity, Breast Health Center and Department of Surgery, Linz, Austria. Electronic address: ruth.helfgott@ordensklinikum.at.
2. Medical University Vienna and Cancer Comprehensive Center, Department of Bioinformatic and Statistic, Austria.
3. Department of Radiology, Linz, Austria.
4. Department of Pathology, Linz, Austria.
5. Department of Nuclear Medicine, Linz, Austria.
6. Sisters of Charity, Breast Health Center and Department of Surgery, Linz, Austria.
7. St Gallen Breast Health Center, Austria.
8. Medical University Vienna and Cancer Comprehensive Center, Department of Surgery, Austria.

Abstract

INTRODUCTION:

Axillary ultrasound staging (AUS) is an important tool to guide clinical decisions in breast cancer therapy, especially regarding axillary surgery but also radiation therapy. It is unknown whether biological subtypes influence axillary staging using ultrasound (AUS).

METHOD:

This is a retrospective single center analysis. All patients with breast cancer, a preoperative axillary ultrasound and a complete surgical axillary staging were included between 1999 and 2014, except patients with neoadjuvant chemotherapy (NACT). The results of the AUS were compared with final pathological results. Biological subtypes were identified by immunohistochemistry.

RESULTS:

583 women were included in the study. Sensitivity, Specificity, positive and negative predictive value for AUS were 39%, 96%, 91% and 83%. While sensitivity was significantly lower in Luminal A and B patients (25.0%; 39.8%) as compared to non Luminal breast cancer patients (TN 68.8%; Her2+ 71.4%; p = 0.0032), there were no significant differences between the groups with respect to specificity, PPV and NPV.

CONCLUSION:

Solely regarding sensitivity of AUS, our study could show significant differences between biological subtypes of breast cancer with lower sensitivity in Luminal patients. While PPV was excellent, standing for a low overtreatment rate using AUS for clinical decision making, sensitivity was poor overall, comparable to the results of other studies.

Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

PMID: 30366878 [Indexed for MEDLINE]

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7.

Breast Cancer Res Treat. 2018 Dec;172(3):545-550. doi: 10.1007/s10549-018-4945-1. Epub 2018 Sep 14.

The St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017: Egyptian view.

Khaled H¹, Gamal H², Lotayef M³, Knauer M⁴, Thürliman B⁴.

Author information:
1. Medical Oncology, National Cancer Institute, Cairo University, Fom El-Khalig Square, Cairo, 11796, Egypt. Khussein528@gmail.com.
2. Surgical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
3. Radiation Oncology Departments, National Cancer Institute, Cairo University, Cairo, Egypt.
4. Breast Center, Kantonsspital St. Gallen, St. Gallen, Switzerland.

Abstract

PURPOSE:

The theme of the 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria was about seeking where appropriate to escalate or de-escalate therapies for early breast cancer based on the up-to-date information of loco-regional and systemic therapies. Along with this line, a group of Egyptian experts decided to arrange for a consensus session to elicit the differences and similarities in therapy recommendations for early breast cancer in Egypt compared to the original Saint Gallen voting and recommendations.

METHODS:

During the Egyptian National Cancer Institute's Annual Congress held in November 2017, 30 Egyptian scientists and clinicians from different specialties gathered in a special session and voted on the same questions of the original 15th St. Gallen consensus. Therapies were discussed from different aspects including their intensity, duration, and side effects, and were correlated with tumor stage and tumor biology.

RESULTS AND CONCLUSIONS:

This report summarizes the voting questions and resulting percentages of answers of the Egyptian scientists. Interestingly the differences were minimal between the Cairo and original Saint Gallen Consensus denoting a more global view of breast cancer management all over the world.

PMID: 30218194 [Indexed for MEDLINE]

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8.

Lancet Oncol. 2018 Oct;19(10):1385-1393. doi: 10.1016/S1470-2045(18)30380-2. Epub 2018 Sep 5.

Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial.

Galimberti V¹, Cole BF², Viale G³, Veronesi P⁴, Vicini E⁵, Intra M⁵, Mazzarol G⁶, Massarut S⁷, Zgajnar J⁸, Taffurelli M⁹, Littlejohn D¹⁰, Knauer M¹¹, Tondini C¹², Di Leo A¹³, Colleoni M⁵, Regan MM¹⁴, Coates AS¹⁵, Gelber RD¹⁶, Goldhirsch A¹⁷; International Breast Cancer Study Group Trial 23-01.

Collaborators: (183)

Boyle F, Jerusalem G, Stahel R, Aebi S, Green M, Karlsson P, Kössler I, Láng I, Hiltbrunner A, Bernhard J, Fournarakou S, Kammler R, Maibach R, Rabaglio M, Ribi K, Roschitzki H, Roux S, Ruepp B, Mahoney C, Price K, Blacher L, Scolese T, Scott K, Lippert S, Zielinski T, Mastropasqua M, Andrighetto S, Dell'Orto P, Renne G, Pruneri G, Dellapasqua S, Iorfida M, Cancello G, Montagna E, Cardillo A, Peruzzotti G, Ghisini R, Luini A, Veronesi U, Intra M, Gentilini O, Zurrida S, Curigliano G, Nole F, Orecchia R, Leonardi MC, Baratella P, Chifu C, Sargenti M, Crivellari D, Morassut S, Mileto M, Piccoli E, Veronesi A, Magri MD, Buonadonna A, Candiani E, Carbone A, Perin T, Volpe R, Roncadin M, Arcicasa M, Coran F, Lagrassa M, Recalcati A, Limonta ME, Tricomi P, Fenaroli P, Candiago E, Cattaneo L, Gianatti A, Santini D, Maweja S, Delvenne P, Rorive A, Collignon J, Garbay JR, Mathieu MC, Galatius H, Hoffmann J, Schousen P, Lanng C, Hoerby J, Bruun Rasmussen B, Holtveg H, Moeller Talman ML, Abugattas JE, Cotrina JM, Dyer R, Lindtner J, Majdic E, Frkovic-Grazio S, Oehlschlegel C, Ries G, Töpfer M, Lorenz U, Schiltknecht O, Späti B, Ehrsam A, Bamert M, Egli-Tupaj M, Rageth C, Saurenmann E, Tausch C, Caduff R, Moch H, Varga Z, Sarlos D, Kralidis E, Grobholz R, Pagani O, Bronz L, Ghielmini M, Mazzucchelli L, Rusca T, Gyr T, Leidi L, Caccia G, Wyss D, Fey MF, Müller M, Günthert A, Berclaz G, Fleischmann A, Delaloye JF, Treboux A, Lehr HA, Fiche M, Perey L, Zaman L, Jeanneret Sozzi W, Forbes J, Lindsay DF, Preece DF, Hill J, Jeal P, Smart P, Collins J, Mann GB, Millar R, Murphy C, Buchanan M, Murugasu A, French J, Elder E, Mann L, Moon D, Bilous AM, Pathmanathan N, Howard V, Gill PG, Kollias J, Bochner M, Madigan L, Rippy E, Whitfield R, Farshidi F, Moore K, Sywak M, Tan L, Ross W, Briscoe K, Jones A, Shah A, Lim E, Macindoe R, Spillane A, Moore K, Bonar SF, Carmalt H, West R, Mak C, McKenzie P, Harman R, Gerred S, Juhasz E, Allpress S, Craik J, Campbell I, Chin P, Hayes L, Mayall F, Thorburn M.

Author information:
1. Division of Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address: viviana.galimberti@ieo.it.
2. IBCSG Statistical Center and Department of Mathematics and Statistics, University of Vermont, Burlington, VT, USA.
3. International Breast Cancer Study Group (IBCSG) Central Pathology Office, Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy; University of Milan, Milan, Italy.
4. Division of Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy; University of Milan, Milan, Italy.
5. Division of Senology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
6. International Breast Cancer Study Group (IBCSG) Central Pathology Office, Division of Pathology and Laboratory Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy.
7. Centro di Riferimento Oncologico, Aviano, Italy.
8. Department of Surgical Oncology, Institute of Oncology, Ljubljana, Slovenia.
9. Orsola Hospital and University of Bologna, Bologna, Italy.
10. Riverina Cancer Care Centre, Wagga Wagga, NSW, Australia.
11. Breast Center St Gallen, Kantonsspital, St Gallen, Switzerland.
12. Department of Medical Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
13. Hospital of Prato-AUSL Toscana Centro, Istituto Toscano Tumori, Prato, Italy.
14. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
15. IBCSG and University of Sydney, Sydney, NSW, Australia.
16. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Harvard T H Chan School of Public Health, Boston, MA, USA; Frontier Science and Technology Research Foundation, Boston, MA, USA.
17. IBCSG and European Institute of Oncology, Milan, Italy.

Comment in

• More evidence for further minimisation of breast-cancer surgery. [Lancet Oncol. 2018]

Abstract

BACKGROUND:

We previously reported the 5-year results of the phase 3 IBCSG 23-01 trial comparing disease-free survival in patients with breast cancer with one or more micrometastatic (≤2 mm) sentinel nodes randomly assigned to either axillary dissection or no axillary dissection. The results showed no difference in disease-free survival between the groups and showed non-inferiority of no axillary dissection relative to axillary dissection. The current analysis presents the results of the study after a median follow-up of 9·7 years (IQR 7·8-12·7).

METHODS:

In this multicentre, randomised, controlled, open-label, non-inferiority, phase 3 trial, participants were recruited from 27 hospitals and cancer centres in nine countries. Eligible women could be of any age with clinical, mammographic, ultrasonographic, or pathological diagnosis of breast cancer with largest lesion diameter of 5 cm or smaller, and one or more metastatic sentinel nodes, all of which were 2 mm or smaller and with no extracapsular extension. Patients were randomly assigned (1:1) before surgery (mastectomy or breast-conserving surgery) to no axillary dissection or axillary dissection using permuted blocks generated by a web-based congruence algorithm, with stratification by centre and menopausal status. The protocol-specified primary endpoint was disease-free survival, analysed in the intention-to-treat population (as randomly assigned). Safety was assessed in all randomly assigned patients who received their allocated treatment (as treated). We did a one-sided test for non-inferiority of no axillary dissection by comparing the observed hazard ratios (HRs) for disease-free survival with a margin of 1·25. This 10-year follow-up analysis was not prespecified in the trial's protocol and thus was not adjusted for multiple, sequential testing. This trial is registered with ClinicalTrials.gov, number NCT00072293.

FINDINGS:

Between April 1, 2001, and Feb 8, 2010, 6681 patients were screened and 934 randomly assigned to no axillary dissection (n=469) or axillary dissection (n=465). Three patients were ineligible and were excluded from the trial after randomisation. Disease-free survival at 10 years was 76·8% (95% CI 72·5-81·0) in the no axillary dissection group, compared with 74·9% (70·5-79·3) in the axillary dissection group (HR 0·85, 95% CI 0·65-1·11; log-rank p=0·24; p=0·0024 for non-inferiority). Long-term surgical complications included lymphoedema of any grade in 16 (4%) of 453 patients in the no axillary dissection group and 60 (13%) of 447 in the axillary dissection group, sensory neuropathy of any grade in 57 (13%) in the no axillary dissection group versus 85 (19%) in the axillary dissection group, and motor neuropathy of any grade (14 [3%] in the no axillary dissection group vs 40 [9%] in the axillary dissection group). One serious adverse event (postoperative infection and inflamed axilla requiring hospital admission) was attributed to axillary dissection; the event resolved without sequelae.

INTERPRETATION:

The findings of the IBCSG 23-01 trial after a median follow-up of 9·7 years (IQR 7·8-12·7) corroborate those obtained at 5 years and are consistent with those of the 10-year follow-up analysis of the Z0011 trial. Together, these findings support the current practice of not doing an axillary dissection when the tumour burden in the sentinel nodes is minimal or moderate in patients with early breast cancer.

FUNDING:

International Breast Cancer Study Group.

Copyright © 2018 Elsevier Ltd. All rights reserved.

PMID: 30196031 [Indexed for MEDLINE]

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9.

Breast Cancer Res Treat. 2018 Dec;172(3):523-537. doi: 10.1007/s10549-018-4937-1. Epub 2018 Sep 4.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

Weber WP^1,2, Haug M^3,4, Kurzeder C^3,4, Bjelic-Radisic V^5,6, Koller R⁷, Reitsamer R⁸, Fitzal F⁹, Biazus J¹⁰, Brenelli F¹¹, Urban C¹², Paulinelli RR¹³, Blohmer JU¹⁴, Heil J¹⁵, Hoffmann J¹⁶, Matrai Z¹⁷, Catanuto G¹⁸, Galimberti V¹⁹, Gentilini O²⁰, Barry M²¹, Hadar T²², Allweis TM²³, Olsha O²², Cardoso MJ²⁴, Gouveia PF²⁴, Rubio IT²⁵, de Boniface J^26,27, Svensjö T²⁸, Bucher S²⁹, Dubsky P^9,30, Farhadi J³¹, Fehr MK³², Fulco I^3,4,33, Ganz-Blättler U³⁴, Günthert A³⁵, Harder Y³⁶, Hauser N³³, Kappos EA^3,4, Knauer M³⁷, Landin J^3,4, Mechera R^3,4, Meani F³⁸, Montagna G^3,4, Ritter M^3,4, Saccilotto R^4,39, Schwab FD^3,4, Steffens D^3,4, Tausch C³¹, Zeindler J^3,4, Soysal SD^3,4, Lohsiriwat V⁴⁰, Kovacs T⁴¹, Tansley A⁴², Wyld L⁴³, Romics L⁴⁴, El-Tamer M⁴⁵, Pusic AL⁴⁶, Sacchini V⁴⁵, Gnant M⁹.

Author information:
1. Breast Center, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland. walter.weber@usb.ch.
2. University of Basel, Basel, Switzerland. walter.weber@usb.ch.
3. Breast Center, University Hospital Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
4. University of Basel, Basel, Switzerland.
5. Department of Gynecology, Medical University of Graz, Graz, Austria.
6. Sektion Senologie, Helios Klinikum Wuppertal GmbH, University Hospital of University Witten/Herdecke, Wuppertal, Germany.
7. Department of Plastic and Reconstructive Surgery, Wilhelminenspital, Vienna, Austria.
8. Breast Center Salzburg, University Clinic Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria.
9. Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
10. Breast Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
11. Breast Oncology Division, University of Campinas, Campinas, SP, Brazil.
12. Positivo University Medical School, Curitiba, Brazil.
13. Gynecology and Breast Unit, Goiás Anticancer Association, Hospital Araújo Jorge, Goiânia, Brazil.
14. Department of Gynecology and Breast Center, Charité University Hospital, Berlin, Germany.
15. Department of Obstetrics and Gynecology, Medical School, University of Heidelberg, Heidelberg, Germany.
16. Breast Center, University Hospital Düsseldorf, Düsseldorf, Germany.
17. Department of Breast and Sarcoma Surgery, National Institute of Oncology, Budapest, Hungary.
18. Multidisciplinary Breast Unit, Azienda Ospedaliera Cannizzaro, Catania, Italy.
19. Division of Breast Surgery, European Institute of Oncology, Milan, Italy.
20. Breast Surgery Unit, San Raffaele Hospital, Milan, Italy.
21. Mater Misericordiae University Hospital, Dublin, Ireland.
22. Breast Health Unit, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel.
23. Department of Surgery, Kaplan Medical Center, Rehovot, Israel.
24. Breast Unit, Champalimaud Clinical Centre, Champalimaud Foundation, Lisbon, Portugal.
25. Breast Surgical Oncology, Clinica Universidad de Navarra, Madrid, Spain.
26. Department of Surgery, Capio St Göran's Hospital, Stockholm, Sweden.
27. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
28. Department of Surgery, Central Hospital, Kristianstad, Sweden.
29. Breast Center, Lucerne Cantonal Hospital, Lucerne, Switzerland.
30. Breast Center, Hirslanden Clinic St. Anna, Lucerne, Switzerland.
31. Breast Center Zurich, Zurich, Switzerland.
32. Breast Center Thurgau, Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland.
33. Breast Center, Hirslanden Clinic Aarau, Aarau, Switzerland.
34. Institute of Sociology, University of St. Gallen, St. Gallen, Switzerland.
35. Department of Gynecology, Lucerne Cantonal Hospital, Lucerne, Switzerland.
36. Department of Plastic, Reconstructive and Aesthetic Surgery, Centro di Senologia della Svizzera Italiana (CSSI), Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
37. Breast Center St. Gallen, St. Gallen, Switzerland.
38. Department of Obstetrics and Gynecology, Centro di Senologia della Svizzera Italiana (CSSI), Ospedale Regionale di Lugano, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
39. Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
40. Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
41. Breast Surgery Unit, Guy's Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
42. Department of Surgery, Royal Liverpool University Hospital, Liverpool, UK.
43. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
44. Department of Surgery, New Victoria Hospital, Glasgow, UK.
45. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
46. Division of Plastic and Reconstructive Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Abstract

PURPOSE:

Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.

METHODS:

The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.

RESULTS:

Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.

CONCLUSIONS:

In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

PMCID: PMC6245050 Free PMC Article

PMID: 30182349 [Indexed for MEDLINE]

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10.

Ann Surg Oncol. 2018 Sep;25(9):2632-2640. doi: 10.1245/s10434-018-6556-9. Epub 2018 Jun 8.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

Weber WP¹, Tausch C², Hayoz S³, Fehr MK⁴, Ribi K^3,5, Hawle H³, Lupatsch JE⁶, Matter-Walstra K⁶, Chiesa F^2,7, Dedes KJ⁸, Berclaz G⁹, Lelièvre L¹⁰, Hess T¹¹, Güth U^2,11, Pioch V¹², Sarlos D¹³, Leo C¹⁴, Canonica C¹⁵, Gabriel N¹⁶, Zeindler J¹⁷, Cassoly E³, Andrieu C³, Soysal SD¹⁷, Ruhstaller T⁷, Fehr PM¹⁸, Knauer M⁷; Swiss Group for Clinical Cancer Research (SAKK).

Author information:
1. Breast Center, University Hospital Basel, University of Basel, Basel, Switzerland. walter.weber@usb.ch.
2. Breast Center Zürich, Zurich, Switzerland.
3. SAKK Coordinating Center, Bern, Switzerland.
4. Cantonal Hospital Frauenfeld, Frauenfeld, Switzerland.
5. IBCSG Coordinating Center, Bern, Switzerland.
6. Institute of Pharmaceutical Medicine, University of Basel, Basel, Switzerland.
7. Breast Center St. Gallen, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
8. Breast Cancer Center, Comprehensive Cancer Center Zurich, University Hospital of Zurich, Zurich, Switzerland.
9. Breast Center Bern Lindenhofgruppe, Bern, Switzerland.
10. Centre du sein, Centre Hospitalier Universitaire Vaudois - CHUV, Lausanne, Switzerland.
11. Cantonal Hospital Winterthur, Winterthur, Switzerland.
12. ZeTuP St. Gallen, St. Gallen, Switzerland.
13. Cantonal Hospital Aarau, Aarau, Switzerland.
14. Cantonal Hospital Baden, Baden, Switzerland.
15. IOSI Bellinzona, Bellinzona, Switzerland.
16. City Hospital Triemli, Zurich, Switzerland.
17. Breast Center, University Hospital Basel, University of Basel, Basel, Switzerland.
18. Breast Center Graubünden, Cantonal Hospital Graubünden, Chur, Switzerland.

Abstract

BACKGROUND:

Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer.

METHODS:

In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil^® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage.

RESULTS:

Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil^® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil^® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil^®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil^® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil^® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2].

CONCLUSIONS:

TachoSil^® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

PMID: 29948418 [Indexed for MEDLINE]

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11.

Ann Surg. 2018 Apr 24. doi: 10.1097/SLA.0000000000002771. [Epub ahead of print]

Impact of Breast Surgery in Primary Metastasized Breast Cancer: Outcomes of the Prospective Randomized Phase III ABCSG-28 POSYTIVE Trial.

Fitzal F¹, Bjelic-Radisic V², Knauer M³, Steger G^4,5, Hubalek M⁶, Balic M⁷, Singer C⁸, Bartsch R⁹, Schrenk P¹⁰, Soelkner L¹¹, Greil R¹², Gnant M¹; ABCSG.

Author information:
1. Department of Surgery, Medical University, Vienna, Austria.
2. Department of Gynecology, Medical University, Graz, Austria.
3. Breast Health Center, St Gallen, Austria.
4. Medical Oncology, Medical University, Vienna, Austria.
5. Gaston H. Glock Research Center, Medical University, Vienna, Austria.
6. Department of Gynecology, Breast Health Center Hall, Tirol, Austria.
7. Medical Oncology, Medical University, Graz, Austria.
8. Gynecology, Medical University, Graz, Austria.
9. German Breast Group, Breast Health Center Hall, Tirol, Austria.
10. Department of Surgery, Medical University, Linz, Austria.
11. Austrian Breast and Colorectal Cancer Study Group, Medical University, Linz, Austria.
12. Department of Medical Oncology, Paracelsus Medical University, Salzburg, Austria.

Abstract

BACKGROUND:

Conflicting evidence exists regarding the value of surgical resection of the primary in stage IV breast cancer patients.

OBJECTIVE:

The prospective randomized phase III ABCSG-28 POSYTIVE trial evaluated median survival comparing primary surgery followed by systemic therapy to primary systemic therapy in de novo stage IV breast cancer.

METHODS:

Between 2011 and 2015, 90 previously untreated stage IV breast cancer patients were randomly assigned to surgical resection of the primary tumor followed by systemic therapy (Arm A) or primary systemic therapy (Arm B) in Austria. Overall survival (OS) was defined as the primary study endpoint.

RESULTS:

The trial was stopped early due to poor recruitment. Ninety patients (45 arm A, 45 arm B) were included; median follow-up was 37.5 months. Patients in the surgery arm had more cT3 breast cancer (22.2% vs 6.7%) and more cN2 staging (15.6% vs 4.4%). Both groups were well balanced with respect to the type of first-line systemic treatment. Median survival in arm A was 34.6 months, versus 54.8 months in the nonsurgery arm [hazard ratio (HR) 0.691, 95% confidence interval (95% CI) 0.358-1.333; P = 0.267]; time to distant progression was 13.9 months in the surgery arm and 29.0 months in the nonsurgery arm (HR 0.598, 95% CI 0.343-1.043; P = 0.0668).

CONCLUSION:

The prospective phase III trial ABCSG-28 (POSYTIVE) could not demonstrate an OS benefit for surgical resection of the primary in breast cancer patients presenting with de novo stage IV disease.

PMID: 29697452

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12.

Oncoimmunology. 2018 Jan 3;7(4):e1414129. doi: 10.1080/2162402X.2017.1414129. eCollection 2018.

Interleukin 7-expressing fibroblasts promote breast cancer growth through sustenance of tumor cell stemness.

Boesch M¹, Onder L¹, Cheng HW¹, Novkovic M¹, Mörbe U¹, Sopper S², Gastl G², Jochum W³, Ruhstaller T⁴, Knauer M⁴, Ludewig B¹.

Author information:
1. Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacherstrasse 95, St. Gallen, Switzerland.
2. Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, Austria.
3. Institute of Pathology, Kantonsspital St. Gallen, Rorschacherstrasse 95, St. Gallen, Switzerland.
4. Breast Center, Kantonsspital St. Gallen, Rorschacherstrasse 95, St. Gallen, Switzerland.

Abstract

The tumor microenvironment harbors cancer-associated fibroblasts that function as major modulators of cancer progression. Here, we assessed to which extent distinct cancer-associated fibroblast subsets impact mammary carcinoma growth and cancer cell stemness in an orthotopic murine model. We found that fibroblasts expressing the Cre recombinase under the control of the interleukin 7 promoter occupied mainly the tumor margin where they physically interacted with tumor cells. Intratumoral ablation of interleukin 7-expressing fibroblasts impaired breast tumor growth and reduced the clonogenic potential of cancer cells. Moreover, cDNA expression profiling revealed a distinct oncogenic signature of interleukin 7-producing fibroblasts. In particular, Cxcl12 expression was strongly enhanced in interleukin 7-producing fibroblasts and cell type-specific genetic ablation and systemic pharmacological inhibition revealed that the CXCL12/CXCR4 axis impacts breast tumor cell stemness. Elevated expression of CXCL12 and other stem cell factors in primary human breast cancer-associated fibroblasts indicates that certain fibroblast populations support tumor cell stemness and thereby promote breast cancer growth.

PMCID: PMC5889213 Free PMC Article

PMID: 29632733

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13.

Breast Cancer Res Treat. 2017 Aug;165(1):139-149. doi: 10.1007/s10549-017-4314-5. Epub 2017 Jun 3.

First international consensus conference on standardization of oncoplastic breast conserving surgery.

Weber WP¹, Soysal SD², El-Tamer M³, Sacchini V³, Knauer M⁴, Tausch C⁵, Hauser N⁶, Günthert A⁷, Harder Y⁸, Kappos EA², Schwab F², Fitzal F⁹, Dubsky P^10,9, Bjelic-Radisic V¹¹, Reitsamer R¹², Koller R¹³, Heil J¹⁴, Hahn M¹⁵, Blohmer JU¹⁶, Hoffmann J¹⁷, Solbach C¹⁸, Heitmann C¹⁹, Gerber B²⁰, Haug M², Kurzeder C².

Author information:
1. Breast Center, University Hospital Basel, Basel, Switzerland. walter.weber@usb.ch.
2. Breast Center, University Hospital Basel, Basel, Switzerland.
3. Memorial Sloan Kettering Cancer Center, New York, USA.
4. Breast Center St. Gallen, St. Gallen, Switzerland.
5. Breast-Center Zurich, Zurich, Switzerland.
6. Breast Center Hirslanden Clinics Aarau Cham Zug and frauenarztzentrum aargau ag, Baden, Switzerland.
7. Department of Obstetrics and Gynecology, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
8. Division of Plastic, Reconstructive and Aesthetic Surgery, Ospedale Regionale di Lugano (ORL), Breast Centre of Switzerland (CSSI), Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
9. Department of Surgery and Comprehensive Cancer Center Vienna, Medical University Vienna, Vienna, Austria.
10. Breast Center, Hirslanden Klinik St. Anna, Lucerne, Switzerland.
11. Department of Gynecology, Medical Univerisity Graz, Auenbruggerplatz 14, 8036, Graz, Austria.
12. Breast Center Salzburg, University Clinic Salzburg, Paracelsus Medical University Salzburg, Salzburg, Austria.
13. Plastische, Ästhetische und Rekonstruktive Chirurgie, Wilhelminenspital der Stadt, Vienna, Austria.
14. Universitäts-Brustzentrum, Universitäts-Frauenklinik, Im Neuenheimer Feld 440, Heidelberg, Germany.
15. Department of Women's Health, University Breast Center Tubingen, Tübingen, Germany.
16. Gynecology with Breast Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
17. Breast Center, University Hospital Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
18. Breast Center, University Hospital Frankfurt, Frankfurt, Germany.
19. Breast Center at the English Garden, Munich, Germany.
20. Breast Surgery Unit at the Department of Ob/Gyn, University Hospital Rostock, Suedring 81, 18059, Rostock, Germany.

Abstract

PURPOSE:

To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from the German, Austrian and Swiss societies of senology.

METHODS:

A total of 52 questions were addressed by electronic voting. The panel's recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained.

RESULTS:

The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient.

CONCLUSIONS:

When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.

PMID: 28578506 [Indexed for MEDLINE]

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14.

Breast Care (Basel). 2014 Oct;9(5):319-22. doi: 10.1159/000368760.

Adjuvant bisphosphonates in breast cancer treatment.

Knauer M¹, Thürlimann B¹.

Author information:
1. Breast Center St. Gallen, Switzerland.

Abstract

Several solid tumors like breast cancer tend to spread to the bone, where the microenvironment is especially receptive to the tumor by special interactions between bone cells and tumor cells. Bone metastases often lead to skeletal-related events with significant morbidity and mortality. The therapy of bone metastases and osteoporosis with bisphosphonates (BPs) has been established many years ago as a standard treatment. In the adjuvant setting, cancer treatment-induced bone loss is a frequent cause of morbidity, and prevention and treatment of this condition with BPs and the monoclonal antibody denosumab are also well established. Besides postmenopausal patients, several studies including 2 larger studies by the Austrian Breast and Colorectal Cancer Study Group (ABCSG) and the Cancer and Leukemia Group B (CALGB) have shown an increase in bone mineral density in premenopausal women. BPs as anticancer treatment are, however, still controversial because several studies yielded conflicting results, with beneficial effects only in subgroups of patients. The publication of the latest Oxford overview of prospective trials is being awaited; at the presentation of the results, a 34% relative reduction of bone metastasis and a 17% improvement in overall survival was demonstrated in the subgroup of postmenopausal patients. These results will likely lead to an incorporation of the use of BPs into routine adjuvant breast cancer treatment.

PMCID: PMC4322690 Free PMC Article

PMID: 25759611

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15.

Ann Oncol. 2015 Feb;26(2):313-20. doi: 10.1093/annonc/mdu544. Epub 2014 Nov 17.

Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12.

Gnant M¹, Mlineritsch B², Stoeger H³, Luschin-Ebengreuth G³, Knauer M⁴, Moik M², Jakesz R⁵, Seifert M⁵, Taucher S⁶, Bjelic-Radisic V³, Balic M³, Eidtmann H⁷, Eiermann W⁸, Steger G⁵, Kwasny W⁹, Dubsky P⁵, Selim U¹⁰, Fitzal F⁵, Hochreiner G¹¹, Wette V¹², Sevelda P¹³, Ploner F³, Bartsch R⁵, Fesl C¹⁴, Greil R²; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.

Author information:
1. Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna michael.gnant@meduniwien.ac.at.
2. Department of Internal Medicine III, Paracelsus Medical University Salzburg, Salzburg.
3. Clinical Department of Oncology, Medical University of Graz, Graz.
4. Department of General and Visceral Surgery, Hospital of the Sisters of Charity, Linz.
5. Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna.
6. Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria.
7. Gynecology and Obstetrics Clinic, University of Schleswig-Holstein, Kiel.
8. Gynecology and Gynecological Oncology, IOZ-München, Munich, Germany.
9. Department of Surgery, Wiener Neustadt Hospital, Wiener Neustadt.
10. Department of Surgery, Hanusch Hospital, Vienna.
11. Center of Hematology and Medical Oncology, General Hospital Linz, Linz.
12. Department of Surgery, Practice of Dr Wette, Sankt Veit an der Glan.
13. Hospital Hietzing, Vienna.
14. Department of Statistics, Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria.

Comment in

• Duration of endocrine therapy and its impact on the results of adjuvant trials in premenopausal breast cancer patients. [Ann Oncol. 2015]

Abstract

BACKGROUND:

Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months.

PATIENTS AND METHODS:

Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points.

RESULTS:

After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw.

CONCLUSION:

These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term.

CLINICALTRIALSGOV:

NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PMID: 25403582 [Indexed for MEDLINE]

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16.

Trials. 2014 Jun 20;15:239. doi: 10.1186/1745-6215-15-239.

Comparison of a standard CO₂ pressure pneumoperitoneum insufflator versus AirSeal: study protocol of a randomized controlled trial.

Luketina RR¹, Knauer M, Köhler G, Koch OO, Strasser K, Egger M, Emmanuel K.

Author information:
1. Department of General and Visceral Surgery, Krankenhaus der Barmherzigen Schwestern Linz, Seilerstätte 4, Linz 4020, Austria. ruzica-rosalia.luketina@bhs.at.

Abstract

BACKGROUND:

AirSeal is a novel class of valve-free insufflation system that enables a stable pneumoperitoneum with continuous smoke evacuation and carbon dioxide (CO₂) recirculation during laparoscopic surgery. Comparison data to standard CO₂ pressure pneumoperitoneum insufflators is scarce. The aim of this study is to evaluate the potential advantages of AirSeal compared to a standard CO₂ insufflator.

METHODS/DESIGN:

This is a single center randomized controlled trial comparing elective laparoscopic cholecystectomy, colorectal surgery and hernia repair with AirSeal (group A) versus a standard CO₂ pressure insufflator (group S). Patients are randomized using a web-based central randomization and registration system. Primary outcome measures will be operative time and level of postoperative shoulder pain by using the visual analog score (VAS). Secondary outcomes include the evaluation of immunological values through blood tests, anesthesiological parameters, surgical side effects and length of hospital stay. Taking into account an expected dropout rate of 5%, the total number of patients is 182 (n = 91 per group). All tests will be two-sided with a confidence level of 95% (P <0.05).

DISCUSSION:

The duration of an operation is an important factor in reducing the patient's exposure to CO₂ pneumoperitoneum and its adverse consequences. This trial will help to evaluate if the announced advantages of AirSeal, such as clear sight of the operative site and an exceptionally stable working environment, will facilitate the course of selected procedures and influence operation time and patients clinical outcome.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01740011, registered 23 November 2012.

PMCID: PMC4078359 Free PMC Article

PMID: 24950720 [Indexed for MEDLINE]

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17.

Breast Care (Basel). 2014 May;9(2):97-100. doi: 10.1159/000362482.

Late recurrences in early breast cancer: for whom and how long is endocrine therapy beneficial?

Knauer M¹, Filipits M², Dubsky P³.

Author information:
1. Breast Center St. Gallen, Switzerland.
2. Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Austria.
3. Department of Surgery, Comprehensive Cancer Center, Medical University Vienna, Austria.

Abstract

During the last decade, besides the well-established clinical-pathological predictors for the risk of late recurrence in breast cancer, such as estrogen receptor status, and T and N stage, a variety of multigene assays have been shown to improve prognostication and prediction in this setting. Several clinical trials have evaluated the role of extended endocrine therapy with tamoxifen (ATLAS) or aromatase inhibitors (MA.17, NSABP-B33 and ABCSG 6a), and other randomized studies are still ongoing. However, among this patient population, it is still not clear who could benefit from extended therapy and what the optimal treatment duration should be. New multigene assays such as EndoPredict, PAM50 ROR-score, HOXB13/IL17BR ratio and Breast Cancer Index provide significant and relevant prognostic information concerning the likelihood of recurrence beyond 5 years after surgery. The identified low-risk subgroups not only show a very favorable prognosis, they also seem to have only little benefit from extended aromatase inhibitor therapy. Many of these reverse transcriptase/polymerase chain reaction-based techniques have been validated in archived tumor material from large phase III trials, and will soon be available to routine pathology laboratories as an aid in clinical decision-making for patients.

PMCID: PMC4038313 Free PMC Article

PMID: 24944551

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18.

Clin Cancer Res. 2014 Mar 1;20(5):1298-305. doi: 10.1158/1078-0432.CCR-13-1845. Epub 2014 Feb 11.

The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer.

Filipits M¹, Nielsen TO, Rudas M, Greil R, Stöger H, Jakesz R, Bago-Horvath Z, Dietze O, Regitnig P, Gruber-Rossipal C, Müller-Holzner E, Singer CF, Mlineritsch B, Dubsky P, Bauernhofer T, Hubalek M, Knauer M, Trapl H, Fesl C, Schaper C, Ferree S, Liu S, Cowens JW, Gnant M; Austrian Breast and Colorectal Cancer Study Group.

Author information:
1. Authors' Affiliations: Departments of Medicine I, Pathology, and Surgery; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna; Austrian Breast and Colorectal Cancer Study Group, Vienna; Departments of Internal Medicine III and Pathology, Paracelsus Private Medical University, Salzburg; Departments of Internal Medicine and Pathology, Medical University of Graz, Graz; Departments of Pathology and Surgery, Sisters of Charity Hospital and Cancer Center, Linz; Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck; Department of Surgery, General Hospital Baden, Baden, Austria; Myraqa, Redwood Shores, California; NanoString Technologies, Seattle, Washington; and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Abstract

PURPOSE:

To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients.

EXPERIMENTAL DESIGN:

The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.

RESULTS:

PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ(2) 15.32, P < 0.001; ROR-based risk groups: ΔLRχ(2) 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease.

CONCLUSION:

PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors.

©2014 AACR

Free Article

PMID: 24520097 [Indexed for MEDLINE]

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19.

Ann Oncol. 2014 Feb;25(2):339-45. doi: 10.1093/annonc/mdt494. Epub 2013 Dec 16.

Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone.

Gnant M¹, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z, Mlineritsch B, Kwasny W, Knauer M, Singer C, Jakesz R, Dubsky P, Fitzal F, Bartsch R, Steger G, Balic M, Ressler S, Cowens JW, Storhoff J, Ferree S, Schaper C, Liu S, Fesl C, Nielsen TO; Austrian Breast and Colorectal Cancer Study Group.

Collaborators: (8)

Fohler H, Klucky B, Steiner K, Gao D, Barry G, Huntsman DG, Parker A, Tsang P.

Author information:
1. Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Abstract

BACKGROUND:

PAM50 is a 50-gene test that is designed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been developed to be carried out in qualified routine hospital pathology laboratories.

PATIENTS AND METHODS:

One thousand four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial were entered into this study. Patients did not receive adjuvant chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50 test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR score were calculated. The primary analysis was designed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables.

RESULTS:

In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P<0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B (P<0.0001). Significant and clinically relevant discrimination between low- and high-risk groups occurred also within all tested subgroups.

CONCLUSION(S):

The results of the primary analysis, in combination with recently published results from the ATAC trial, constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A 10-year metastasis risk of <3.5% in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome-this finding could help to avoid unwarranted overtreatment.

CLINICAL TRIAL NUMBER:

ABCSG 8: NCT00291759.

PMID: 24347518 [Indexed for MEDLINE]

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20.

Eur J Cancer. 2013 Dec;49(18):3773-9. doi: 10.1016/j.ejca.2013.08.001. Epub 2013 Aug 27.

Prospective cost-effectiveness analysis of genomic profiling in breast cancer.

Retèl VP¹, Joore MA, Drukker CA, Bueno-de-Mesquita JM, Knauer M, van Tinteren H, Linn SC, van Harten WH.

Author information:
1. Netherlands Cancer Institute (NKI-AVL), Department of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

The cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates.

METHODS:

Costs and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N-) patients included in the RASTER study (n=427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10-30 mm, grade II, age 40-70; (2) ductal, oestrogen receptor-positive, tumour diameter 5-30 mm, grade II/III and age 40-70.

RESULTS:

Based on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature.

CONCLUSIONS:

The use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID: 23992641 [Indexed for MEDLINE]

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21.

Int J Cancer. 2013 Aug 15;133(4):929-36. doi: 10.1002/ijc.28082. Epub 2013 Mar 4.

A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study.

Drukker CA¹, Bueno-de-Mesquita JM, Retèl VP, van Harten WH, van Tinteren H, Wesseling J, Roumen RM, Knauer M, van 't Veer LJ, Sonke GS, Rutgers EJ, van de Vijver MJ, Linn SC.

Author information:
1. Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Abstract

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1-3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n = 219) and high-risk (n = 208) patients were 97.0% and 91.7%. The 5-year DRFI probabilities for AOL low-risk (n = 132) and high-risk (n = 295) patients were 96.7% and 93.4%. For 70-gene signature low-risk-AOL high-risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.

Copyright © 2013 UICC.

PMCID: PMC3734625 Free PMC Article

PMID: 23371464 [Indexed for MEDLINE]

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22.

Q J Nucl Med Mol Imaging. 2012 Oct;56(5):447-58.

Imaging of bone metastases in prostate cancer: an update.

Langsteger W¹, Haim S, Knauer M, Waldenberger P, Emmanuel K, Loidl W, Wolf I, Beheshti M.

Author information:
1. Department of Nuclear Medicine and Endocrinology, PET - CT Center Linz, Linz, Austria.

Abstract

Assessing bone metastases is often beyond the scope of plain - film radiography, and nuclear imaging in particular with bone scintigraphy has proved the mainstay for detection of bony disease for over 40 years. Bone scanning with 99mTechnetium - labeled diphosphonates relies on the detection of pathological osteoblastic response elicited from malignant cells. This technique offers the advantage of whole body examination, low cost, availability and high sensitivity. However, it suffers from relative low specificity. The addition of single-photon emission computed tomography (SPECT) to bone scintigraphy has markedly improved the diagnostic benefit. Although the accuracy of SPECT is significantly higher than that of planar scintigraphy, there is still room for improvement of anatomic localization and morphological characterization, a limitation that has currently been mainly overcome with the upcoming of combined SPECT-CT (computed tomography). Positron emission tomography (PET), a modality with higher spatial resolution than that of SPECT can be particularly helpful in detecting small lesions. Moreover, PET imaging using various specific radiotracers has the advantage of detecting malignant disease in both bone and soft tissues. It is highly sensitive mainly in detecting early bone marrow as well as for diagnosing lytic bony metastases and can be also reliably used to monitor therapy response. In this review, we present the current role of SPECT and PET in the imaging of skeletal metastases from prostate cancer.

PMID: 23069924 [Indexed for MEDLINE]

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23.

Breast Care (Basel). 2012 Feb;7(1):61-66. Epub 2012 Feb 20.

Results of the First Austrian Multidisciplinary Expert Panel on Controversies in Local Treatment of Breast Cancer.

Knauer M¹, Gnant M, Fitzal F.

Author information:
1. Breast Cancer Center, Department of Surgery, Sisters of Charity Hospital, Linz.

Abstract

At the first Austrian multidisciplinary expert panel on controversies in local treatment of breast cancer, 22 experts of all relevant disciplines discussed current areas of debate (surgery of the breast, surgery and pathology of the axilla, reconstructive surgery, radiotherapy, and imaging) in local therapy. The most controversial area of debate was the area of axillary surgery. The panel agreed that it was no longer necessary to perform completion axillary lymph node dissection (ALND) when micrometastases are diagnosed in the sentinel lymph node. The only prospective trial comparing patients with sentinel node macrometastases with or without completion ALND had to be terminated early due to failure in sufficient patient recruitment. As long as the frequently discussed issues have not been solved and in light of the lack of any clear level 1 evidence, the panel decided not to recommend omitting axillary dissection in patients with 1 or 2 macrometastases meeting the inclusion criteria of the ACOSOG Z0011 trial. The Austrian panel similarly decided not to recommend omitting axillary dissection in patients with macrometastases and low-risk breast cancer in general. These decisions reflect the increasing skepticism of the scientific community against rapidly shifting paradigms without sufficient and clear evidence.

PMCID: PMC3335360 Free PMC Article

PMID: 22553475

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24.

Br J Cancer. 2012 Jan 31;106(3):440-6. doi: 10.1038/bjc.2011.597. Epub 2012 Jan 10.

Brain metastases free survival differs between breast cancer subtypes.

Berghoff A¹, Bago-Horvath Z, De Vries C, Dubsky P, Pluschnig U, Rudas M, Rottenfusser A, Knauer M, Eiter H, Fitzal F, Dieckmann K, Mader RM, Gnant M, Zielinski CC, Steger GG, Preusser M, Bartsch R.

Author information:
1. Comprehensive Cancer Center Vienna, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Abstract

BACKGROUND:

Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010.

METHODS:

Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test.

RESULTS:

Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014).

CONCLUSION:

Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.

PMCID: PMC3273356 Free PMC Article

PMID: 22233926 [Indexed for MEDLINE]

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25.

Breast Cancer Res Treat. 2011 Dec;130(3):725-34. doi: 10.1007/s10549-011-1748-z. Epub 2011 Sep 4.

Impact of mammographic screening on the detection of good and poor prognosis breast cancers.

Esserman LJ¹, Shieh Y, Rutgers EJ, Knauer M, Retèl VP, Mook S, Glas AM, Moore DH, Linn S, van Leeuwen FE, van 't Veer LJ.

Author information:
1. University California San Francisco, San Francisco, CA, USA. Laura.esserman@ucsfmedctr.org

Abstract

We sought to compare the molecular signature of node negative cancers from two cohorts 15 years apart, to determine if there is molecular evidence of increase in low and ultralow risk cancers over time. We studied the impact of age, time period of diagnosis, and mammographic screening on biology of tumors where The Netherlands Cancer Institute 70-gene prognosis signature was generated as part of 2 validation series, one retrospective (1984-1992), Cohort 1, and one prospective (2004-2006), Cohort 2. A total of 866 patients were analyzed. Regardless of time period of diagnosis, the proportion of T1, grade 1, hormone receptor positive (HR) tumors, and good prognosis by 70-gene signature significantly increases as age increases (P < 0.01). In women aged 49-60, the time period of diagnosis significantly affects the proportion of cancers that were NKI 70-gene low risk: 40.6% (67/165) compared with 58% (119/205) for Cohorts 1 and 2, respectively. This is in contrast to the absence of a significant change for women under age 40, where 25% (17/68) and 30% (17/56) were low risk in Cohorts 1 and 2, respectively. In women aged 49-60, using an ultralow risk threshold of the 70-gene signature, 10% of tumors in Cohort 1 were ultralow risk compared with 30% for women with screen-detected cancers in Cohort 2. Older age and method of detection (screening) are associated with a higher likelihood of a biologically low risk tumor. In women over age 50, biologically low risk tumors are frequent and tools that classify risk may minimize overtreatment.

PMCID: PMC5646368 Free PMC Article

PMID: 21892702 [Indexed for MEDLINE]

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26.

Br J Cancer. 2010 Dec 7;103(12):1788-93. doi: 10.1038/sj.bjc.6605916. Epub 2010 Nov 16.

Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature.

Knauer M¹, Cardoso F, Wesseling J, Bedard PL, Linn SC, Rutgers EJ, van 't Veer LJ.

Author information:
1. Division of Diagnostic Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, Amsterdam NL-1066CX, The Netherlands.

Abstract

BACKGROUND:

overexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome.

METHODS:

in all, 168 T1-3, N0-1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy.

RESULTS:

in the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7, P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03) and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively.

INTERPRETATION:

the 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome.

2010 Cancer Resaerch UK.

PMCID: PMC3008599 Free PMC Article

PMID: 21081926 [Indexed for MEDLINE]

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27.

Eur J Cancer. 2010 May;46(8):1382-91. doi: 10.1016/j.ejca.2010.02.035. Epub 2010 Mar 30.

Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer.

Retèl VP¹, Joore MA, Knauer M, Linn SC, Hauptmann M, Harten WH.

Author information:
1. Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Department of Psychosocial Research and Epidemiology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Abstract

BACKGROUND:

The 70-gene signature (MammaPrint) is a prognostic test used to guide adjuvant treatment decisions in patients with node-negative breast cancer. In order to decide upon its use, a systematic comparative analysis of the effects of the 70-gene signature, the Sankt Gallen guidelines and the Adjuvant Online Software for these patients on survival, quality of life and costs is warranted.

METHODS:

A Markov decision model was used to simulate the 20-year costs and outcomes (survival and quality-of-life adjusted survival (QALYs)) in a hypothetical cohort of node-negative, estrogen receptor positive breast cancer patients. Sensitivity and specificity of the three prognostic tools were based on 5 and 10 years breast cancer specific survival and distant metastasis as first event, derived from a pooled analysis consisting of 305 tumour samples from 3 previously reported validation studies concerning the 70-gene signature.

RESULTS:

Small differences in survival, but substantial differences in quality-adjusted survival between the prognostic tools were observed. Quality-adjusted survival was highest when using the 70-gene signature. Based on costs per QALY, the 70-gene has the highest probability of being cost-effective for a willingness to pay for a QALY higher than euro12.000. Sankt Gallen showed the highest survival rates compared to the 70-gene signature, but leads to a substantial larger amount of adjuvant chemotherapy and lower cost-effectiveness, thus demanding a high willingness to pay to save a life year.

CONCLUSIONS:

When deciding upon the cost-effectiveness of the prognostic tests, the 70-gene signature improves quality-adjusted survival and has the highest probability of being cost-effective.

Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID: 20359886 [Indexed for MEDLINE]

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28.

Breast Cancer Res Treat. 2010 Apr;120(3):655-61. doi: 10.1007/s10549-010-0814-2. Epub 2010 Mar 5.

The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer.

Knauer M¹, Mook S, Rutgers EJ, Bender RA, Hauptmann M, van de Vijver MJ, Koornstra RH, Bueno-de-Mesquita JM, Linn SC, van 't Veer LJ.

Author information:
1. Division of Diagnostic Oncology, Netherlands Cancer Institute, Plesmanlaan, Amsterdam, The Netherlands. m.knauer@nki.nl

Abstract

Multigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET (n = 315) or ET + CT (n = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07-4.98; P = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07-0.59; P < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03-2.02; P = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17-0.71; P < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful.

PMID: 20204499 [Indexed for MEDLINE]

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29.

Ann Surg Oncol. 2010 May;17(5):1406-13. doi: 10.1245/s10434-009-0902-x. Epub 2010 Jan 22.

Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature.

Mook S¹, Knauer M, Bueno-de-Mesquita JM, Retel VP, Wesseling J, Linn SC, Van't Veer LJ, Rutgers EJ.

Author information:
1. Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

Mammographic screening and increased awareness has led to an increase in the detection of T1 breast tumors that are generally estimated as having low risk of recurrence after locoregional treatment. However, even small tumors can metastasize, which leaves us with the question for the necessity of adjuvant treatment. Therefore, additional prognostic markers are needed to tailor adjuvant systemic treatment for these relatively low-risk patients. The aim of our study was to evaluate the accuracy of the 70-gene MammaPrint signature in T1 breast cancer.

MATERIALS AND METHODS:

We selected 964 patients from previously reported studies with pT1 tumors (<or=2 cm). Frozen tumor samples were hybridized on the 70-gene signature array at the time of the initial study and classified as having good prognosis or poor prognosis.

RESULTS:

The median follow-up was 7.1 years (range 0.2-25.2). The 10-year distant metastasis-free (DMFS) and breast cancer specific survival (BCSS) probabilities were 87% (SE 2%) and 91% (SE 2%), respectively, for the good prognosis-signature group (n = 525), and 72% (SE 3%) and 72% (SE 3%), respectively, for the poor prognosis-signature group (n = 439). The signature was an independent prognostic factor for BCSS at 10 years (multivariate hazard ratio [HR] 3.25 [95% confidence interval, CI, 1.92-5.51; P < .001]). Moreover, the 70-gene MammaPrint signature predicted DMFS at 10 years for 139 patients with pT1ab cancers (HR 3.45 [95% CI 1.04-11.50, P = .04]).

CONCLUSIONS:

The 70-gene MammaPrint signature is an independent prognostic factor in patients with pT1 tumors and can help to individualize adjuvant treatment recommendation in this increasing breast cancer population.

PMID: 20094918 [Indexed for MEDLINE]

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30.

Oncol Rep. 2009 May;21(5):1283-7.

Different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.

Winder T¹, Mündlein A, Rhomberg S, Dirschmid K, Hartmann BL, Knauer M, Drexel H, Wenzl E, De Vries A, Lang A.

Author information:
1. Department of Medicine, Academic Teaching Hospital Feldkirch, A-6807 Feldkirch, Austria. thomas.winder@lkhf.at

Abstract

A glycine to valine substitution at codon 12 (G12V) in Kirsten-Ras (K-Ras) gene has been associated with reduced overall survival in colorectal cancer patients; however, the effect of other K-Ras mutations than G12V still remains unclear. Therefore, we investigated the role of different K-Ras mutations on overall survival in a homogeneous, large patient cohort with standardized therapy and uniform analysis of K-Ras mutation status. The study included 342 patients with histopathologically proven colorectal cancer. Survival data were provided by the federal agency for statistics in Austria. Occurrence of K-Ras mutations at codons 12, 13 and 61 were determined by capillary sequencing. The overall K-Ras mutation frequency in carcinoma tissue was 28%. Carriers of the G12V mutation at the K-Ras gene showed a significantly decreased overall survival compared to carriers of the wild-type [HR=2.56 (1.15-5.69)]. Other mutations than G12V were associated with better overall survival compared to wild-type [HR=0.44 (0.2-0.99)]. In conclusion, for the first time, our study showed clearly that different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.

PMID: 19360305 [Indexed for MEDLINE]

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31.

Eur J Surg Oncol. 2009 Aug;35(8):798-804. doi: 10.1016/j.ejso.2008.10.001. Epub 2008 Nov 14.

Adjuvant extension of chemotherapy after neoadjuvant therapy may not improve outcome in early-stage breast cancer.

Knauer M¹, Haid A, Schneider Y, Köberle-Wührer R, Lang A, Winder T, Alton R, Jasarevic Z, Säly C, Offner FA, Wenzl E, deVries A.

Author information:
1. Department of General and Thoracic Surgery, University Teaching Hospital Feldkirch, Feldkirch, Austria. michael.knauer@lkhf.at

Abstract

INTRODUCTION:

Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS).

PATIENTS AND METHODS:

From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3-6 cycles of epirubicin+docetaxel, AdC comprised EC+/-taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months.

RESULTS:

After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p=0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p=0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p=0.008), loco-regional and distant recurrence-rates (HR 3.0, p=0.03 and HR 2.0, p=0.02).

DISCUSSION:

In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.

PMID: 19013747 [Indexed for MEDLINE]

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32.

World J Surg Oncol. 2007 Oct 11;5:114.

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome.

Knauer M¹, Haid A, Ammann K, Lang A, Offner F, Türtscher M, Cerkl P, Wenzl E.

Author information:
1. Department of General and Thoracic Surgery, General Hospital of Feldkirch, Academic Teaching Hospital, Feldkirch, Austria. knaui@gmx.at.

Abstract

BACKGROUND:

Different molecular therapies like the EGFR-inhibiting antibody cetuximab have come into clinical practice. Cetuximab is EMEA-approved for metastatic colorectal cancer and advanced squamous-cell head and neck cancer. Administration is said to be safe and well tolerated with common, usually mild dermatologic side effects.

CASE PRESENTATION:

We present the case of a patient with fatal complications after oesophagectomy and neoadjuvant chemotherapy including cetuximab for squamous-cell esophageal cancer. A transthoracic en-bloc oesophagectomy was performed. Few days later the patient died due to gas exchange dysfunction and circulation instability after a previously unseen combination of drain-erosion of the stomach with subsequent pleurisy and air leak of the left main bronchus.

CONCLUSION:

So far we have never observed this fatal combination of drain erosion of the stomach with fibrinous pleurisy and unmanageable progressive tracheal defect before. The role of cetuximab in the multifactorial aetiology of damages of stomach and trachea after oesophagectomy remains unclear since we are not able to link the complication directly to cetuximab or definitely exclude it as a sole surgical complication. Clinicians should be aware of the possibility of fatal side effects and careful recording of all complications is necessary in ongoing and planned studies to obtain more evidence about safety and tolerance of targeted therapies.

PMCID: PMC2147013 Free PMC Article

PMID: 17927839

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33.

Breast Cancer Res Treat. 2008 Jul;110(2):395-6. Epub 2007 Sep 13.

Standardization of pathologic complete response rates in breast cancer treatment.

Knauer M, Devries A, Wenzl E, Haid A.

PMID: 17851755 [Indexed for MEDLINE]

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34.

Ann Surg Oncol. 2007 Nov;14(11):3090-101. Epub 2007 Jun 26.

Intra-operative sonography: a valuable aid during breast-conserving surgery for occult breast cancer.

Haid A¹, Knauer M, Dunzinger S, Jasarevic Z, Köberle-Wührer R, Schuster A, Toeppker M, Haid B, Wenzl E, Offner F.

Author information:
1. Department of General and Thoracic Surgery, Landeskrankenhaus Feldkirch, Teaching Hospital of Innsbruck University, Carinagasse 47-49, 6800, Feldkirch, Austria. anton.haid@cable.vol.at

Abstract

BACKGROUND:

Breast cancer is increasingly detected during an early non-palpable stage. Together with pre-operative marking of the mass, intra-operative imaging provides invaluable clues. This study was designed to evaluate the usefulness of intra-operative sonography in the hands of the surgeon.

METHODS:

Between July 2001 and October 2006, 567 patients underwent treatment for operable breast cancer at the landeskrankenhaus (LHK) Feldkirch. Three hundred and sixty lesions were not palpable. Two hundred and ninety-nine patients with poorly definable or non-definable lesions well seen by ultrasound imaging underwent intra-operative sonography (group 1), while 61 patients with non-palpable lesions only seen on mammography (group 2) were subjected to pre-operative needle localization. The study was non-randomized with prospective data acquisition

RESULTS:

All lesions were identified by both sonography and pre-operative needle localization. In the ultrasound group (group 1) 81% of the lesions were successfully removed by primary intention without metachronous secondary surgery versus 62% in group 2 (p < 0.00228). Eighty-eight percent of the lesions in group 1 were eligible for breast-conserving surgery versus 75% in group 2. The mean clear margin in group 1 was substantially smaller (4.8 mm) than in group 2 (7.2 mm) (p < 0.0001).

CONCLUSION:

Intra-operative sonography proved to be a reliable and helpful tool in the hands of the surgeon, not only for tumor localization, but also for orientation during tumor excision. It simplifies organizational work and spares the patient the discomfort of pre-operative needle localization.

PMID: 17593330 [Indexed for MEDLINE]

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35.

J Clin Oncol. 2006 Jul 20;24(21):3374-80.

Multicentric breast cancer: a new indication for sentinel node biopsy--a multi-institutional validation study.

Knauer M¹, Konstantiniuk P, Haid A, Wenzl E, Riegler-Keil M, Pöstlberger S, Reitsamer R, Schrenk P.

Author information:
1. Department of Surgery, General Hospital, Feldkirch, Austria. michael.knauer@lkhf.at

Abstract

PURPOSE:

Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer.

PATIENTS AND METHODS:

Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB.

RESULTS:

Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates.

CONCLUSION:

Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.

PMID: 16849751 [Indexed for MEDLINE]

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36.

Eur J Surg Oncol. 2006 Dec;32(10):1180-5. Epub 2006 Jun 5.

Medium-term follow-up data after sentinel node biopsy alone for breast cancer.

Haid A¹, Knauer M, Köberle-Wührer R, Ammann K, Koller L, Eiter H, Lang A, Wenzl E.

Author information:
1. Department of General and Thoracic Surgery, Landeskrankenhaus Feldkirch, Vorarlberg, Affiliated teaching hospital of Innsbruck Medical University, Carinagasse 47-49, A-6800 Feldkirch, Austria. anton.haid@cable.vol.at

Abstract

AIMS:

In patients with early breast cancer sentinel node biopsy (SNB) proved to be an accurate procedure for axillary staging with significantly reduced morbidity. Medium- and long-term observational studies are needed to establish, whether SNB alone is able to prevent locoregional recurrence without impairing long-term survival.

METHODS:

298 patients with invasive breast cancer were subjected to SNB in a prospective audit. Lymphatic mapping was performed with blue dye and radiocolloids. 180 patients had SNB alone (group 1), while 118 subsequently underwent axillary dissection (AD; group 2). In ten patients AD was omitted despite the tumor burden in the SN. Clinical follow-up studies were performed at regular intervals. The mean follow-up time was 47months in group 1 (range 7-90) and 46months in group two (range 1-87months).

RESULTS:

Sentinel nodes were identified in 286 out of 298 patients (96%). One patient in group 1 developed axillary and simultaneous supraclavicular lymph node recurrence. After AD regional relapses have so far not been observed. One ipsilateral local recurrence was detected in each group. Five patients in group 1 and 15 patients in group 2 developed distant metastases. Three out of six and eight out of nine patients, respectively, died of their advanced disease. All patients with SN tumor infiltration not subjected to AD are alive and well.

CONCLUSIONS:

Axillary recurrence is rare after sentinel node biopsy alone. Its rate is comparable to that after AD, even in patients with SN micrometastases. These conclusions are confirmed by reports in the literature.

PMID: 16750344 [Indexed for MEDLINE]

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37.

Wien Klin Wochenschr. 2005 Sep;117(17):610-4.

[Mesenteric inflammatory veno-occlusive disease (MIVOD)--a rare cause of intestinal ischemia].

[Article in German]

Knauer M¹, Haid A, Gruber-Mösenbacher U, Wenzl E.

Author information:
1. Abteilung für Allgemein und Thoraxchirurgie, Landeskrankenhaus Feldkirch, Feldkirch, Osterreich. michael.knauer@lkhf.at

Abstract

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a relatively recently known and not very often diagnosed form of ischemic bowel disease of low incidence und unknown etiology. We present the case of a patient who after presentation of inconclusive signs of epigastric pain and rectal bleeding suddenly developed right abdominal pain with local peritonism. Suspecting intestinal ischemia or perforated appendicitis we first performed laparoscopy, which showed an inflammable tumor of cecum, ascending colon and appendix with massive adhesions to the abdominal wall. We performed an open right hemicolectomy with primary anastomosis. The patient developed a deep vein thrombosis of the vena tibialis post. and vena saphena parva. After 12 months our patient is free of complaints and recurrence. Investigations carried out showed no evidence of hypercoagulopathy. The presentation of MIVOD can range from chronic inflammatory bowel disease with recurrent abdominal pain in combination with nausea, emesis and bloody diarrhea to acute abdomen. Therefore diagnostic misinterpretation and mistherapy as well as underdiagnosis is common. Histologic investigation shows a variable inflammatory infiltration of multiple veins of the intestinal wall and the mesentery as well as thrombotic vessel occlusion in different stages without involvement of the arteries. All forms of hypercoagulopathy, parasitic disease, sepsis and malignancy have to be excluded. Therapeutic success can only be achieved with surgical resection of the affected bowel, whereon in general no recurrence will occur.

PMID: 16395991 [Indexed for MEDLINE]

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38.

Wien Klin Wochenschr. 2005 Feb;117(4):121-8.

[Sentinel node biopsy in breast cancer: techniques and indications].

[Article in German]

Haid A¹, Knauer M, Köberle-Wührer R, Wenzl E.

Author information:
1. Abteilung für Allgemein- und Thoraxchirurgie am Landeskrankenhaus Feldkirch, Feldkirch. anton.haid@cable.vol.at

Abstract

Sentinel node biopsy (SNB) has proved to be a useful and accurate procedure for lymph node staging in breast cancer and melanoma and should be standard of care in the treatment of these tumors. In other malignancies (colon, rectum, stomach, esophagus, head and neck and thyroid, cervix uteri) it is still under investigation. SNB in breast cancer was accepted as a sole and reliable diagnostic method in breast cancer from the panel of distinguished experts at the 8th international conference of primary therapy of early breast cancer 2003 in St. Gallen. Combination of the current techniques with radiocolloids and blue dye, applicated superficially (intradermal, subdermal, peri- and subareolar) and deeply (peritumoral, intratumoral, subtumoral) enables high identification rates and negative predictive values. It should be performed by teams consisting of surgeons, pathologists and nuclear medicine specialists with appropriate training and experience. Accepted indications are uni- and multifocal tumors smaller than 3 cm without suspicious findings in the axilla, furthermore SNB is indicated in patients with large ductal carcinoma in situ (>2cm) and/or with assumed microinvasion. Albeit SNB could be shown to be safe after preoperative chemotherapy and in multicentric breast cancer, due to lack of sufficient data it is still under discussion in these cases. Expedience of this procedure in other lymph node basins, along the mammaria interna vessels or in the infra- and supraclavicular region is considered to be at an investigative stage as well. SNB allows the pathologist to focus on a small number of nodes most likely to contain metastases. Application of serial sectioning and immunhistochemistry results in a more accurate staging than routine examination. Detection of additional micrometastases that are found in 10-15% leads to an upgrading from N0 to N1. Broad application and refurbishment led to scientific discussion of prognostic importance of micrometastases and its relevance according axillary dissection and adjuvant systemic treatment. Although many unicentric and multicentric observational studies validated by complete axillary dissection could demonstrate that SNB is accurate and suitable for all operable clinically node-negative breast cancers, longterm results and especially the incidence of axillary recurrence and its sequelae are outstanding. Findings of ongoing large prospective randomized trials like NSABP 32, Z0010 and Z0011 of the American College of Surgeons (ACOSOG), the AMAROS-Trial of the European Organisation of Research and Treatment of Cancer (EORTC) and the ALMANAC-Trial of the British Association of Surgical Oncology (BASO) will give a conclusive answer. Significant improvement in morbidity and quality of life measurements could be revealed several times in unicentric and even in muticentric studies like ALMANAC. Sentinel node biopsy is a team approach, requirements are good cooperation and well-defined stuctures of quality indicators and documentation. Participation in national clinical studies is recommended.

PMID: 15847190 [Indexed for MEDLINE]

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39.

Eur J Surg Oncol. 2002 Nov;28(7):705-10.

Shoulder-arm morbidity following axillary dissection and sentinel node only biopsy for breast cancer.

Haid A¹, Kuehn T, Konstantiniuk P, Köberle-Wührer R, Knauer M, Kreienberg R, Zimmermann G.

Author information:
1. Department of General and Thoracic Surgery, Landeskrankenhaus Feldkirch, Austria. anton.haid@cable.vol.at

Abstract

AIMS:

The purpose of this study was to examine the outcome of shoulder-arm morbidity in patients with breast cancer after various axillary staging procedures. We used a new specific summation score to compare conventional axillary node dissection (AD) and sentinel node only biopsy for postoperative shoulder-arm morbidity.

METHODS:

Eighty-five patients undergoing conventional AD and 66 patients undergoing sentinel node biopsy were evaluated both subjectively (questionnaire) and objectively (clinical examination) for reduced muscle strength, limited range of motion, lymphedema and pain, dysesthesias and loss of sensitivity. The symptoms elicited were rated by their severity with a single summation score describing all symptoms reported.

RESULTS:

Subjective evaluation of patients undergoing breast conserving surgery showed a highly significant difference in favor of SNB only (P< or =0.002). On clinical examination the outcome of patients with SNB only was also significantly or highly significantly better (difference in arm volume:P =0.007; difference in arm muscle strength: P=0.016; loss of sensitivity: P<0.001). Of a total score of 100 (=no symptoms), the mean for AD patients was 80.2 vs 92.8 for SNB patients (P=0.001). In patients undergoing total mastectomy the difference was only significant for pain sensations and total scores.

CONCLUSIONS:

SNB appears to reduce morbidity. Summation scores are a suitable and practicable tool for describing the symptoms associated with axillary surgery.

PMID: 12431466 [Indexed for MEDLINE]

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40.

Breast Cancer Res Treat. 2002 May;73(1):31-6.

Morbidity of breast cancer patients following complete axillary dissection or sentinel node biopsy only: a comparative evaluation.

Haid A¹, Köberle-Wührer R, Knauer M, Burtscher J, Fritzsche H, Peschina W, Jasarevic Z, Ammann M, Hergan K, Sturn H, Zimmermann G.

Author information:
1. Department of General and Thoracic Surgery, Akademisches Lehrkrankenhaus der Universität Innsbruck, Feldkirch, Austria. anton.haid@cable.vol.at

Abstract

INTRODUCTION:

The usefulness of routine axillary dissection (AD) at levels I-II in breast cancer patients has been questioned for years because of the high postoperative morbidity in the shoulder and arm region, and the increasing number of patients with negative nodes. Sentinel node biopsy (SNB) was hoped both to reduce morbidity and to improve the reliability of staging. This study was designed to provide more evidence in this matter by comparing the follow-up data of patients with AD and those with SNB only.

METHOD:

One hundred forty patients who had undergone AD between 1993 and 1996 were questioned for their subjective and objective symptoms using a questionnaire and subsequently subjected to a clinical examination. Their data were compared with those of 57 patients who had undergone SNB only between 1998 and 2000.

RESULTS:

Local recurrences have not been seen to date. The difference between the two groups in terms of a loss of quality of life was negligible. The differences in overall complaints, number of symptoms, pain, limited range of motion of the operated upper extremity, numbness, paresthesias, and arm swelling as well as perceived disability in activities of daily living were significantly in favor of SNB. The length of hospital stay was significantly shorter for SNB patients.

CONCLUSION:

SNB appears to be an accurate procedure for axillary nodal staging in breast cancer patients and is associated with reduced postoperative morbidity and length of hospital stay. But it is still investigational and should not be implemented as therapeutical standard before results of randomized trials are published.

PMID: 12083629 [Indexed for MEDLINE]

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