Publications by authors named "Thorsten Kühn"

65 Publications

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

Cancers (Basel) 2021 Mar 29;13(7). Epub 2021 Mar 29.

Department of Gynecology and Obstetrics, Klinikum Esslingen, 73730 Esslingen, Germany.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).
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http://dx.doi.org/10.3390/cancers13071565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037995PMC
March 2021

A multidisciplinary view of mastectomy and breast reconstruction: Understanding the challenges.

Breast 2021 Apr 10;56:42-52. Epub 2021 Feb 10.

Iridium Kankernetwerk, 2610, Wilrijk-Antwerp, Belgium; University of Antwerp, Faculty of Medicine and Health Sciences, 2610, Wilrijk-Antwerp, Belgium.

The current review paper was written in collaboration with breast cancer surgeons from the European Breast Cancer Research Association of Surgical Trialists (EUBREAST), a breast pathologist from the Danish Breast Cancer Group (DBCG), and representatives from the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer course. Herein we summarize the different mastectomies and reconstruction procedures and define high-risk anatomical areas for breast cancer recurrences, to further specify the challenges in the surgical procedure, histopathological evaluation, and target volumes in case of postmastectomy irradiation, as recommended by the ESTRO guidelines according to the surgical procedure. The paper has original figures and illustrations for all disciplines for in-depth understanding of the differences between the procedures.
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http://dx.doi.org/10.1016/j.breast.2021.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905468PMC
April 2021

A multidisciplinary approach for autologous breast reconstruction: A narrative (re)view for better management.

Radiother Oncol 2021 04 12;157:263-271. Epub 2021 Feb 12.

Department of Breast and Sarcoma Surgery, National Institute of Oncology, Budapest, Hungary, Budapest, Hungary.

Breast reconstruction and oncoplastic surgery have become an important part of breast cancer care. The use of autologous breast reconstruction (ABR) has evolved significantly with advances in microsurgery, aiming to reduce donor site complications and improve cosmesis. For years, immediate-ABR was considered a contraindication if postmastectomy irradiation (PMRT) was planned. As a result of de-escalation of axillary surgery the indication of PMRT are increasing along-side with observations that PMRT in the setting of ABR is not contraindicated. Surgical techniques may result in different amount and areas of breast residual glandular tissue and patient selection is important to reduce potential residual disease. Meticulus radiation planning is important to potentially reduce complications without compromising oncologic outcomes. Surgical techniques change constantly in aim to improve aesthetic results but should most importantly maintain priority to the oncological indications. By multidisciplinary team work with a comprehensive understanding of each discipline, we can preserve the accomplishments of breast surgery in the setting of PMRT, without compromising disease control.
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http://dx.doi.org/10.1016/j.radonc.2021.01.036DOI Listing
April 2021

Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases - a transSENTINA Analysis.

Geburtshilfe Frauenheilkd 2020 Dec 3;80(12):1229-1236. Epub 2020 Dec 3.

Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.

Among patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), the association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association between these parameters and residual axillary involvement after NACT remains unclear. Patients with clinically occult nodal metastases (i.e. negative by clinical assessment but positive by SLNB prior to NACT, i.e. Arm B of the SENTINA trial) were included in the presented analysis. All patients received a second sentinel lymph node biopsy (SLNB) and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT. Arm B of the SENTINA study contained 360 patients, 318 of which were evaluable for this analysis. After NACT, 71/318 (22.3%) patients had involved SLNs or non-SLNs after NACT. Overall, 71/318 (22.3%) patients achieved a pCR in the breast. Associations of extranodal spread, lack of multifocality and pCR in the breast with residual axillary burden were statistically significant. In a descriptive analysis including all patients with clinically negative axilla before NACT in the SENTINA trial 1.2% of triple negative (TN) patients and 0.5% of HER/2 positive patients had residual axillary disease in case of a breast pCR. Patients in the SENTINA trial with clinically negative axilla and involved SLNs still carried a significant risk of nodal metastases after NACT. However, the risk of residual axillary burden was particularly low in TN and HER/2 positive tumors in case of a breast pCR.
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http://dx.doi.org/10.1055/a-1298-3453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714621PMC
December 2020

Residual disease after mastectomy - Authors' reply.

Lancet Oncol 2020 11;21(11):e501

Iridium Kankernetwerk, University of Antwerp, Antwerp, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(20)30622-7DOI Listing
November 2020

Should we worry about residual disease after mastectomy?

Lancet Oncol 2020 08;21(8):1011-1013

Department of Radiation Oncology, Iridium Kankernetwerk, Antwerp 2610, Belgium; Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium. Electronic address:

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http://dx.doi.org/10.1016/S1470-2045(20)30331-4DOI Listing
August 2020

Spatial location of local recurrences after mastectomy: a systematic review.

Breast Cancer Res Treat 2020 Sep 13;183(2):263-273. Epub 2020 Jul 13.

Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Purpose: We performed a systematic review to document the spatial location of local recurrences (LR) after mastectomy.

Methods: A PubMed search was conducted in August 2019 for the following terms: breast [Title/Abstract] AND cancer [Title/Abstract] AND recurrence [Title/Abstract] AND mastectomy [Title/Abstract]. The search was filtered for English language. Exclusion criteria included studies that did not specify the LR location or studies reporting LR associated with inflammatory breast cancer, or other breast cancers such as phyllodes tumours, lymphoma or associated with sarcoma/angiosarcoma.

Results: A total of 3922 titles were identified, of which 21 publications were eligible for inclusion in the final analysis. A total of 6901 mastectomy patients were included (range 25-1694). The mean LR proportion was 3.5%. Among the total of 351 LR lesions, 81.8% were in the subcutaneous tissue and the skin, while 16% were pectoral muscle recurrences.

Conclusion: Local recurrences are mostly located within the subcutaneous tissue and the skin, assumed to result from unrecognized/subclinical tumour foci left behind after mastectomy, surgical implantation of tumour cells in the wound/scar and/or tumour emboli within the subcutaneous lymphatics. Pectoral muscle recurrences are less frequent and may be attributed to residual disease along the posterior surgical margin and/or lymphatic involvement.
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http://dx.doi.org/10.1007/s10549-020-05774-4DOI Listing
September 2020

Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving Surgery: Results from a Quality Assurance Process Integrated into the INSEMA Trial.

Int J Radiat Oncol Biol Phys 2020 07 11;107(4):683-693. Epub 2020 May 11.

Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany. Electronic address:

Purpose: After publication of the radiation field design in the American College of Surgeons Oncology Group Z0011 trial, a radiation therapy quality assurance review was integrated into the Intergroup-Sentinel-Mamma (INSEMA) trial. We aimed to investigate the role of patient characteristics, extent of axillary surgery, and radiation techniques for dose distribution in ipsilateral axillary levels.

Methods And Materials: INSEMA (NCT02466737) has randomized 5542 patients who underwent breast-conserving surgery. Of these, 276 patients from 108 radiation therapy facilities were included in the central review, using the planning records of the first 3 patients treated at each site.

Results: Of the 276 patients, 41 had major deviations (ie, no axillary contouring or submission of insufficient records) leading to exclusion. A total of 235 (85.1%) radiation therapy planning records were delineated according to the INSEMA protocol, including 9 (3.8%) cases with minor deviations. At least 25% of INSEMA patients were unintentionally treated with ≥95% of the prescribed breast radiation dose in axillary level I. Approximately 50% of patients were irradiated with a median radiation dose of more than 85% of prescription dose in level I. Irradiated volumes and applied doses were significantly lower in levels II and III compared with level I. However, 25% of patients still received a median radiation dose of ≥75% of prescription dose to level II. Subgroup analysis revealed a significant association between incidental radiation dose in the axilla and obesity. Younger age, boost application, and fractionation schedule showed no impact on axillary dose distribution.

Conclusions: Assuming ≥80% of prescribed breast dose as the optimal dose for curative radiation of low-volume disease in axillary lymph nodes, at least 50% of reviewed INSEMA patients received an adequate dose in level I, even with contemporary 3-dimensional techniques. Dose coverage was much less in axillary levels II and III, and far below therapeutically relevant doses.
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http://dx.doi.org/10.1016/j.ijrobp.2020.04.042DOI Listing
July 2020

Neoadjuvant Radio(chemo)therapy for Breast Cancer: An Old Concept Revisited.

Breast Care (Basel) 2020 Apr 14;15(2):112-117. Epub 2020 Apr 14.

Department of Radiation Oncology, Heinrich Heine University Hospital, Düsseldorf, Germany.

Background: The international standard of care for the treatment of high-risk breast cancer (BC) consists of neoadjuvant chemotherapy (NACT) and surgery followed by adjuvant whole breast/chest wall irradiation. In this setting, the time interval from the start of NACT to the end of radiotherapy (RT) is usually postponed to 6 months or longer. In addition to this, a high percentage of capsular fibrosis may occur when breast implants are irradiated. Most of these disadvantages could be avoided by using preoperative RT (PRT). PRT is already the standard of care in several other tumor entities (rectal cancer, esophagus carcinoma, lung cancer, and soft tissue sarcoma). Nevertheless, PRT in BC has been tested in several trials, but randomized prospective trials using modern radiation technology and systemic therapies are lacking. The available evidence summarized in this review indicates that PRT may improve survival and reduce long-term toxicity in patients with a higher risk of recurrence and should be consequently tested in a randomized trial.

Summary: Prospective, randomized trials concerning PRT in high-risk BC are needed. We plan to conduct a NeoRad trial (NACT followed by PRT in high-risk BC).

Key Messages: Prospective, randomized studies concerning PRT in high-risk BC are needed.
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http://dx.doi.org/10.1159/000507041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204855PMC
April 2020

What are the guidelines for immediate breast reconstruction?

Eur J Surg Oncol 2020 Apr 11. Epub 2020 Apr 11.

Department of Gynaecology and Obstetrics, Interdisciplinary Breast Center, Klinikum Esslingen, Germany.

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http://dx.doi.org/10.1016/j.ejso.2020.03.226DOI Listing
April 2020

Locoregional recurrence risk after neoadjuvant chemotherapy: A pooled analysis of nine prospective neoadjuvant breast cancer trials.

Eur J Cancer 2020 05 13;130:92-101. Epub 2020 Mar 13.

German Breast Group Neu-Isenburg, Germany. Electronic address:

Aim: This pooled analysis aimed to evaluate locoregional recurrence (LRR) rates of breast cancer (BC) after neoadjuvant chemotherapy (NACT) and to identify independent LRR predictors.

Methods: 10,075 women with primary BC from nine neoadjuvant trials were included. The primary outcome was the cumulative incidence rate of LRR as the first event after NACT. Distant recurrence, secondary malignancy or death were defined as competing events. For identifying LRR predictors, surgery type, pathological complete response (pCR), BC subtypes and other potential risk factors were evaluated.

Results: Median followup was 67 months (range 0-215), overall LRR rate was 9.5%, 4.1% in pCR versus 9.5% in non-pCR patients. Younger age, clinically positive lymph nodes, G3 tumours, non-pCR and TNBC but not surgery type were independent LRR predictors in multivariate analysis. Among BC subtypes, 5-year cumulative LRR rates were associated with higher risk in non-pCR versus pCR patients, which was significant for HR+/HER2- (5.9% vs 3.9%; HR = 2.32 [95%CI 1.22-4.43]; p = 0.011); HR-/HER2+ (14.8% vs 3.1%; HR = 4.26 [94%CI 2.35-7.71]; p < 0.001) and TNBC (18.5% vs 4.2%; HR = 4.10 [95%CI 2.88-5.82]; p < 0.001) but not for HR+/HER2+ (8.1% vs 4.8%; HR = 1.56 [95%CI 0.85-2.85]; p = 0.150). Within non-pCR subgroup, LRR risk was higher for HR-/HER2+ and TNBC vs HR+/HER2- (HR = 2.05 [95%CI 1.54-2.73]; p < 0.001 and HR = 2.77 [95%CI 2.27-3.39]; p < 0.001, respectively).

Conclusions: This pooled analysis demonstrated that young age, node-positive and G3 tumours, as well as TNBC, and non-pCR significantly increased the risk of LRR after NACT. Hence, there is a clear need to investigate better multimodality therapies in the post-neoadjuvant setting for high-risk patients.
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http://dx.doi.org/10.1016/j.ejca.2020.02.015DOI Listing
May 2020

Theoretical and practical knowledge curriculum for European Breast Surgeons.

Eur J Surg Oncol 2020 04 8;46(4 Pt B):717-736. Epub 2020 Feb 8.

Chair of the BRESO Theoretical Knowledge Working Group & Co-Chair of the BRESO Examination Working Group, United Kingdom. Electronic address:

The Breast Surgery theoretical and practical knowledge curriculum comprehensively describes the knowledge and skills expected of a fully trained breast surgeon practicing in the European Union and European Economic Area (EEA). It forms part of a range of factors that contribute to the delivery of high quality cancer care. It has been developed by a panel of experts from across Europe and has been validated by professional breast surgery societies in Europe. The curriculum maps closely to the syllabus of the Union of European Medical Specialists (UEMS) Breast Surgery Exam, the UK FRCS (breast specialist interest) curriculum and other professional standards across Europe and globally (USA Society of Surgical Oncology, SSO). It is envisioned that this will serve as the basis for breast surgery training, examination and accreditation across Europe to harmonise and raise standards as breast surgery develops as a separate discipline from its parent specialties (general surgery, gynaecology, surgical oncology and plastic surgery). The curriculum is not static but will be revised and updated by the curriculum development group of the European Breast Surgical Oncology Certification group (BRESO) every 2 years.
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http://dx.doi.org/10.1016/j.ejso.2020.01.027DOI Listing
April 2020

Survivors of primary breast cancer 5 years after surgery: follow-up care, long-term problems, and treatment regrets. Results of the prospective BRENDA II-study.

Arch Gynecol Obstet 2020 03 27;301(3):761-767. Epub 2020 Jan 27.

Department of Gynaecology and Obstetrics, University of Ulm, Prittwitzstr 43, 89075, Ulm, Germany.

Purpose: This study aims to answer the questions where breast cancer patients in Germany receive follow-up care (with what types of doctors) and what are the long-term problems and treatment regrets of breast cancer patients.

Methods: In the prospective multicenter cohort study BRENDA II ("Breast Cancer under Evidence-Based Guidelines"), 456 patients with primary breast cancer were sampled consecutively over a period of 4 years (2009-2012) and contacted again 5 years after surgery. Long-term problems were elicited on a 4-point Likert scale ranging from 0 ('not at all') to 3 ('very much').

Results: 82% of the patients receive follow-up (FU) at the private practice gynecologist. In 22%, the initial treating hospital is involved in the FU, and in 20% the general practitioner does this (multiple answers possible). Long-term problems attributed to the treatment were most often related to endocrine therapy (mean 1.29) and to chemotherapy (mean 0.94). Most of the patients were happy to have had radiotherapy (95%). For chemotherapy, endocrine therapy, and antibody therapy, the satisfaction for the treatment decision was 87%, 87%, and 84% respectively. Among patients who reported they regretted having undergone a recommended treatment, it was most often for endocrine therapy (5%) and chemotherapy (4%).

Conclusion: In Germany, different specialists are involved in the patients' FU care for BC. The detection of long-term problems due to BC treatment is an essential part of FU care.
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http://dx.doi.org/10.1007/s00404-020-05437-1DOI Listing
March 2020

Post-Neoadjuvant Therapy.

Breast Care (Basel) 2019 Dec 27;14(6):409-413. Epub 2019 Nov 27.

GBG Forschungs GmbH, Neu-Isenburg, Germany.

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http://dx.doi.org/10.1159/000504661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940439PMC
December 2019

Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019).

Breast Care (Basel) 2019 Oct 17;14(5):315-324. Epub 2019 Sep 17.

Department of Gynecology and Obstetrics, Interdisciplinary Breast Center, Agaplesion Markus Hospital, Frankfurt/M., Germany.

A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynäkologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was "Estimating the magnitude of clinical benefit." The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient.
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http://dx.doi.org/10.1159/000502603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883436PMC
October 2019

Feasibility of a large multi-center translational research project for newly diagnosed breast and ovarian cancer patients with affiliated biobank: the BRandO biology and outcome (BiO)-project.

Arch Gynecol Obstet 2020 01 28;301(1):273-281. Epub 2019 Nov 28.

Department of Gynecology and Obstetrics, University Hospital Ulm, University of Ulm, Prittwitzstr. 43, 89075, Ulm, Germany.

Introduction: Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected.

Methods: The target population includes the German "Alb-Allgäu-Bodensee Region" which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets.

Results: Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients.

Conclusions: The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.
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http://dx.doi.org/10.1007/s00404-019-05395-3DOI Listing
January 2020

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

Breast Care (Basel) 2019 Aug 30;14(4):247-255. Epub 2019 Jul 30.

Brustzentrum, Klinik für Gynäkologie und Geburtshilfe, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany.

Every year the Breast Committee of the , a group of gynecological oncologists specialized in breast cancer and interdisciplinary members specialized in pathology, radiologic diagnostics, medical oncology, and radiation oncology, prepares and updates evidence-based recommendations for the diagnosis and treatment of patients with early and metastatic breast cancer. Every update is performed according to a documented rule-fixed algorithm, by thoroughly reviewing and scoring the recent publications for their scientific validity and clinical relevance. This current publication presents the 2019 update on the recommendations for metastatic breast cancer.
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http://dx.doi.org/10.1159/000500999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751428PMC
August 2019

Post-Mastectomy Radiotherapy After Neoadjuvant Chemotherapy in Breast Cancer: A Pooled Retrospective Analysis of Three Prospective Randomized Trials.

Ann Surg Oncol 2019 Nov 26;26(12):3892-3901. Epub 2019 Jul 26.

German Breast Group, Neu-Isenburg, Germany.

Background: The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that patients with a favorable response to NACT might not benefit from RT after mastectomy.

Methods: A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%).

Results: The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval [CI] 9.0-22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7-14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27-1.0; p = 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis.

Conclusions: Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.
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http://dx.doi.org/10.1245/s10434-019-07635-xDOI Listing
November 2019

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study.

BMC Cancer 2019 Jun 21;19(1):611. Epub 2019 Jun 21.

Department of Gynecology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Universitätsstrasse 21-23, 91054, Erlangen, Germany.

Background: Treatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients.

Methods: EvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12 months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT.

Results: Out of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12 months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30 days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment.

Conclusions: Despite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process.

Trial Registration: Clinical Trials Number: CFEM345DDE19.
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http://dx.doi.org/10.1186/s12885-019-5806-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588890PMC
June 2019

Primary Therapy of Early Breast Cancer: Evidence, Controversies, Consensus: Spectrum of Opinion of German Specialists on the 16th St. Gallen International Breast Cancer Conference (Vienna 2019).

Geburtshilfe Frauenheilkd 2019 Jun 14;79(6):591-604. Epub 2019 Jun 14.

Brustzentrum, Frauenklinik der Universität München (LMU), München, Germany.

The results of the international St. Gallen Consensus Conference for the treatment of patients with primary breast cancer were discussed this year by a working group of leading breast cancer experts in view of the therapy recommendations for everyday clinical practice in Germany. Three of the breast cancer experts are also members of this year's St. Gallen panel. The comparison of the St. Gallen recommendations with the annually updated treatment recommendations of the AGO 2019 as well as the S3 guideline is useful, since the recommendations of the St. Gallen panel represent the opinions of experts from various countries and disciplines. The recommendations of the S3 guideline and AGO are based on evidence-based research of the literature. This year's 16th St. Gallen conference featured the motto "Magnitude of clinical benefit". In addition to the evidence-based data, each therapeutic decision must also undergo a benefit/risk assessment of the patient's individual situation and be discussed with the patient.
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http://dx.doi.org/10.1055/a-0897-6457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570611PMC
June 2019

Association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer: Results from the prospective multicenter BRENDA II study.

Breast J 2019 05 3;25(3):386-392. Epub 2019 Apr 3.

Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

Background: This study examined the association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer.

Patients And Methods: In the prospective multicenter cohort study BRENDA II, patients aged ≥65 years with primary breast cancer were sampled over a period of 4 years (2009-2012). A multiprofessional team (tumor board) discussed recommendation for adjuvant chemotherapy according to the German S3 guideline. Cognitive impairment was screened by the clock-drawing test (CDT) prior to adjuvant treatment.

Results: Two hundred and sixty-three patients were included in the study and CDT data were available for 193 patients. Thirty-one percent of the patients had cognitive impairment with different degree of severity. In high-risk patients (n = 61) tumor board recommendation in favor of chemotherapy was 90% and in intermediate-risk patients (n = 170) 27%. Not receiving recommendation for chemotherapy in spite of guideline recommendation was more frequent in patients with cognitive impairment (67%) vs patients without cognitive impairment (46%) with P = 0.02 (OR 2.4, 95% confidence interval (CI) 1.2-4.9). Age, education, migration background and comorbidities were not associated with chemotherapy recommendation by the tumor board among cognitively impaired patients. Once the tumor board had recommended chemotherapy, application of chemotherapy was similar in both groups of patients with or without cognitive impairment.

Conclusion: Almost one third of older patients with breast cancer are affected by cognitive impairment prior to adjuvant treatment. In these patients, cognitive impairment was associated with tumor board decision against chemotherapy in spite of a positive guideline recommendation.
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http://dx.doi.org/10.1111/tbj.13231DOI Listing
May 2019

Validation of a Nomogram Predicting Non-Sentinel Lymph Node Metastases among Patients with Breast Cancer after Primary Systemic Therapy - a transSENTINA Substudy.

Breast Care (Basel) 2018 Dec 6;13(6):440-446. Epub 2018 Nov 6.

Interdisciplinary Breast Centre, Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany.

Background: Prediction of non-sentinel lymph node (SLN) status after primary systemic therapy (PST) may allow tailored axillary staging. The aim of this analysis was to compare established nomograms from i) the primary operative (n = 6) and ii) the neoadjuvant (n = 1) setting with an optimized nomogram to predict non-SLN status in patients after PST.

Methods: 181 patients converting from cN1 prior to PST to ycN0 but found to have a histologically positive SLN in the SENTINA trial were analyzed. Established models were applied. An optimized model was compiled using univariate and subsequent multivariable logistic regression (backward selection, likelihood ratio test).

Results: Area-under-the-curve (AUC) values from the primary operative models showed sufficient performance (0.82-0.71). For the neoadjuvant model, the AUC was found to be inferior to prior analyses (0.66) but within published confidence intervals. The SENTINA nomogram comprised the diameter of the largest lymph node (p = 0.006, odds ratio (OR) = 1.19), tumor size prior to PST (p = 0.085, OR = 1.31), and number of all positive SLN (p = 0.083, OR = 2.04). This model was validated using a separate cohort of arm C (n = 168, AUC 0.79, 95% confidence interval 0.74-0.85).

Conclusion: We validated 7 models of prediction of non-SLN among patients showing axillary conversion through PST. Our own 'SENTINA nomogram' yielded AUC values comparable to previous nomograms.
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http://dx.doi.org/10.1159/000489565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381911PMC
December 2018

Evaluation of soluble carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: A biomarker analysis from the geparquinto phase III neoadjuvant breast cancer trial.

Int J Cancer 2019 08 4;145(3):857-868. Epub 2019 Mar 4.

Department of Oncology, Hematology and Bone Marrow Transplantation with section Pneumology, Hubertus Wald Tumorzentrum, University Comprehensive Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We analyzed the predictive potential of pretreatment soluble carbonic anhydrase IX levels (sCAIX) for the efficacy of bevacizumab in the phase III neoadjuvant GeparQuinto trial. sCAIX was determined by enzyme-linked immunosorbent assay (ELISA). Correlations between sCAIX and pathological complete response (pCR), disease-free and overall survival (DFS, OS) were assessed with logistic and Cox proportional hazard regression models using bootstrapping for robust estimates and internal validation. 1,160 HER2-negative patient sera were analyzed, of whom 577 received bevacizumab. Patients with low pretreatment sCAIX had decreased pCR rates (12.1 vs. 20.1%, p = 0.012) and poorer DFS (adjusted 5-year DFS 71.4 vs. 80.5 months, p = 0.010) compared to patients with high sCAIX when treated with neoadjuvant chemotherapy (NCT). For patients with low sCAIX, pCR rates significantly improved upon addition of bevacizumab to NCT (12.1 vs. 20.4%; p = 0.017), which was not the case in patients with high sCAIX (20.1% for NCT vs. 17.0% for NCT-B, p = 0.913). When analyzing DFS we found that bevacizumab improved 5-year DFS for patients with low sCAIX numerically but not significantly (71.4 vs. 78.5 months; log rank 0.234). In contrast, addition of bevacizumab worsened 5-year DFS for patients with high sCAIX (81 vs. 73.6 months, log-rank 0.025). By assessing sCAIX levels we identified a patient cohort in breast cancer that is potentially undertreated with NCT alone. Bevacizumab improved pCR rates in this group, suggesting sCAIX is a predictive biomarker for bevacizumab with regards to treatment response. Our data also show that bevacizumab is not beneficial in patients with high sCAIX.
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http://dx.doi.org/10.1002/ijc.32163DOI Listing
August 2019

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer.

Authors:
Achim Wöckel Jasmin Festl Tanja Stüber Katharina Brust Mathias Krockenberger Peter U Heuschmann Steffi Jírů-Hillmann Ute-Susann Albert Wilfried Budach Markus Follmann Wolfgang Janni Ina Kopp Rolf Kreienberg Thorsten Kühn Thomas Langer Monika Nothacker Anton Scharl Ingrid Schreer Hartmut Link Jutta Engel Tanja Fehm Joachim Weis Anja Welt Anke Steckelberg Petra Feyer Klaus König Andrea Hahne Traudl Baumgartner Hans H Kreipe Wolfram Trudo Knoefel Michael Denkinger Sara Brucker Diana Lüftner Christian Kubisch Christina Gerlach Annette Lebeau Friederike Siedentopf Cordula Petersen Hans Helge Bartsch Rüdiger Schulz-Wendtland Markus Hahn Volker Hanf Markus Müller-Schimpfle Ulla Henscher Renza Roncarati Alexander Katalinic Christoph Heitmann Christoph Honegger Kerstin Paradies Vesna Bjelic-Radisic Friedrich Degenhardt Frederik Wenz Oliver Rick Dieter Hölzel Matthias Zaiss Gudrun Kemper Volker Budach Carsten Denkert Bernd Gerber Hans Tesch Susanne Hirsmüller Hans-Peter Sinn Jürgen Dunst Karsten Münstedt Ulrich Bick Eva Fallenberg Reina Tholen Roswita Hung Freerk Baumann Matthias W Beckmann Jens Blohmer Peter Fasching Michael P Lux Nadia Harbeck Peyman Hadji Hans Hauner Sylvia Heywang-Köbrunner Jens Huober Jutta Hübner Christian Jackisch Sibylle Loibl Hans-Jürgen Lück Gunter von Minckwitz Volker Möbus Volkmar Müller Ute Nöthlings Marcus Schmidt Rita Schmutzler Andreas Schneeweiss Florian Schütz Elmar Stickeler Christoph Thomssen Michael Untch Simone Wesselmann Arno Bücker Andreas Buck Stephanie Stangl

Geburtshilfe Frauenheilkd 2018 Nov 26;78(11):1056-1088. Epub 2018 Nov 26.

Institut für Klinische Epidemiologie und Biometrie (IKE-B), Universität Würzburg, Würzburg, Germany.

The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.
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http://dx.doi.org/10.1055/a-0646-4630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261741PMC
November 2018

Lymph Nodes in Breast Cancer - What Can We Learn from Translational Research?

Breast Care (Basel) 2018 Oct 25;13(5):342-347. Epub 2018 Sep 25.

Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.

Clinical observations about lack of survival benefit after extensive axillary surgery and biological discordance between primary breast tumors and axillary lymph nodes raise the question of the actual metastatic potential of axillary nodal disease. The exploration of intratumoral heterogeneity and detection of genomic differences between the primary and lymph nodes indicate some similarity between the number of mutations in synchronous axillary node metastases and those in the primary lesion, suggesting a favorable prognosis. The hematogenous route of metastasis needs to be considered in findings of different subclones between nodal and distant metastases. Modern tools such as whole-genome sequencing applied in multiple tumor areas may guide more precisely the extent of axillary surgery.
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http://dx.doi.org/10.1159/000492435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257149PMC
October 2018

Current Status and Future Perspectives of Axillary Management in the Neoadjuvant Setting.

Breast Care (Basel) 2018 Oct 26;13(5):337-341. Epub 2018 Sep 26.

Department of Surgery, Capio St. Göran's Hospital, Stockholm, Sweden.

Axillary surgery has undergone considerable changes in recent years, especially in relation to patients who undergo neoadjuvant chemotherapy (NACT). Due to constantly decreasing rates of recurrence and death from breast cancer, modern surgical strategies aim at de-escalating the extent of local treatment and avoiding unnecessary procedures. This relates especially to lymph node surgery which is associated with considerable morbidity. In patients who initially present with clinically node-negative disease, sentinel lymph node biopsy (SLNB) is increasingly performed after NACT. The determination of the post-NACT nodal status does not only spare patients from additional surgery but also allows the assessment of pathologic complete response which is increasingly becoming an important tool for treatment planning. Since more than 70% of these patients have a ypN0 status after NACT, future trials will aim to identify patients who might be spared any axillary surgery after NACT. In patients who initially present with positive lymph nodes, the success rates of SLNB in terms of detection and accuracy are less favorable compared to those in patients who undergo primary surgery. The clinical significance of this is unclear. To reduce unnecessary axillary dissection in patients with cN1ycN0 status, prospective outcome data after SLNB without further lymph node removal are urgently needed. Improvements in surgical technique by localizing positive nodes at the time of diagnosis and removing them in a targeted surgical procedure (targeted axillary dissection) are under evaluation. Risk assessment and patient selection (including gene expression profiles) might be other ways of safely omitting axillary dissection.
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http://dx.doi.org/10.1159/000492437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257201PMC
October 2018

Lymph Node Management in Breast Cancer: A Highly Dynamic Evolution.

Authors:
Thorsten Kühn

Breast Care (Basel) 2018 Oct 12;13(5):320-322. Epub 2018 Oct 12.

Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany.

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http://dx.doi.org/10.1159/000494043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257206PMC
October 2018