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Introduction To date, the optimal axillary staging procedure for initially node-positive breast carcinoma patients after neoadjuvant chemotherapy (NACT) has been unclear. The aim of the AXSANA study is to prospectively compare different surgical staging techniques with respect to the oncological outcome and quality of life for the patients. Little is known about current clinical practice in Germany. Material and Methods In this paper we analyzed data from patients enrolled in the AXSANA study at German study sites from June 2020 to March 2022. Results During the period under investigation, 1135 patients were recruited at 143 study sites. More than three suspicious lymph nodes were initially found in 22% of patients. The target lymph node (TLN) was marked in 64% of cases. This was done with clips/coils in 83% of patients, with magnetic seeds or carbon suspension in 8% each, and with a radar marker in 1% of patients. After NACT, targeted axillary dissection (TAD) or axillary lymphadenectomy (ALND) were each planned in 48% of patients, and sentinel lymph node biopsy alone (SLNB) in 2%. Clinically, the nodal status after NACT was found to be unremarkable in 65% of cases. Histological lymph node status was correctly assessed by palpation in 65% of patients and by sonography in 69% of patients. Conclusion At the German AXSANA study sites, TAD and ALND are currently used as the most common surgical staging procedures after NACT in initially node-positive breast cancer patients. The TLN is marked with various markers prior to NACT. Given the inadequate accuracy of clinical assessment of axillary lymph node status after NACT, it should be questioned whether axillary dissection after NACT should be performed based on clinical assessment of nodal status alone., Competing Interests: Conflict of Interest/Interessenkonflikt T. D. W. has received fees for lectures and activities from Pfizer, Roche, and NeoDynamics. M. T. has acted in an advisory capacity for Amgen, AstraZeneca, Aurikamed, Becton & Dickinson, BiomʼUp, Celgene, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Lilly, MSD, Norgine, Neodynamics, Novartis, Onkowissen, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, and Sysmex. He received manuscript support from Amgen, Celgene, ClearCut, pfm medical, Roche, and Servier, travel expenses from Amgen, Art Tempi, AstraZeneca, Celgene, Cleracut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Norgine, Novartis, Omniamed, Pfizer, pfm Medical, Roche, and RTI Surgical, conference costs from Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Hexal, Novartis, Pfizer, and Roche, lecturing fees from Amgen, Art Tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Eisai, Genomic Health, Gilead Science, Hexal, I-Med-Institute, Jörg Eickeler, Lilly, MCI, Medtronic, MSD, Novartis, Omniamed, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, Sysmex, and Vifor, and study support from Endomag and Exact Sciences. M. P. L. has acted in an advisory capacity for Lilly, AstraZeneca, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Daiichi Sankyo, Grünenthal, Pierre Fabre, PharmaMar, Samantree, Sysmex, and Roche. He has given lectures for Lilly, Roche, MSD, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Gilead, Grünenthal, AstraZeneca, pfm, Samantree, and Eisai, received travel expenses from Roche and Pfizer, and is on the Editorial Board at medac. S. L. has received fees or research support from Abbvie, AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Roche, and Samsung. In addition, she has acted in an advisory capacity for Abbvie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Daiichi Sankyo, Eirgenix, GlaxoSmithKline, Gilead, Lilly, Merck, Novaris, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, and Seagen, and is a member of GBG Forschungs GmbH. H.-C. K. has received fees and travel expenses support from Carl Zeiss meditec, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Roche, Daiichi Sankyo, Tesaro, MSD, Onkowissen, Eli Lilly, SurgVision, Exact Sciences, and Genomic Health, and holds shares in Theraclion and Phaon Scientific. M. W. has received fees for lectures and consulting activities from Pfizer, Roche, Novartis, Lilly, GlaxoSmithKline, and AstraZeneca. S. P. has received fees for advisory activities from Becton & Dickinson, Grünenthal, Sysmex Deutschland, Sysmex Europe, Endomag, pfm medical AG, NeoNavia, NeoDynamics, and Triconmed, as well as support for training courses from Roche and for travel activities from Motiva. D. W. has received fees for lectures and activities from Roche and Pfizer. M. H. has received lecture fees from Roche and Novartis. M. U. has received fees for lectures and advisory activities from Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiji Sankyo, Eisai, Gilead, GlaxoSmithKline, Lilly, Molecular Health, MSD Merck, Mundipharma, Mylan, Myriad Genetics, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi Aventis, and Saegen. M. B.-P. receives fees for lectures and advisory activities from Roche, Novartis, Pfizer, Eli Lilly, Eisai, GlaxoSmithKline, Seagen, Daiichi Sankyo, pfm medical AG, and AstraZeneca, and study support from Exact Sciences. The AXSANA study is financially supported by the AGO-B, the Claudia von Schilling Foundation for Breast Cancer Research, the Ehmann Foundation Savognin, AWOgyn, EndoMag, Merit Medical GmbH, and Mammotome. The sponsors of the study had no influence on the study protocol or conduct./ T. K. erhielt Honorare für Vorträge und beratende Tätigkeiten von Pfizer, Roche und NeoDynamics. M. T. war beratend tätig für Amgen, AstraZeneca, Aurikamed, Becton & Dickinson, BiomʼUp, Celgene, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Lilly, MSD, Norgine, Neodynamics, Novartis, Onkowissen, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen und Sysmex. Er erhielt Manuskriptunterstützung von Amgen, Celgene, ClearCut, pfm medical, Roche, und Servier, Reisekosten von Amgen, Art Tempi, AstraZeneca, Celgene, Cleracut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Norgine, Novartis, Omniamed, Pfizer, pfm Medical, Roche und RTI Surgical, Kongresskostenübernahmen von Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Hexal, Novartis, Pfizer und Roche, Vortragshonorare von Amgen, Art Tempi, AstraZeneca, Celgene, Clovis, Connect Medica, Eisai, Genomic Health, Gilead Science, Hexal, I-Med-Institute, Jörg Eickeler, Lilly, MCI, Medtronic, MSD, Novartis, Omniamed, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, Sysmex und Vifor und Studienunterstützung von Endomag und Exact Sciences. M. P. L. war beratend für Lilly, AstraZeneca, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Daiichi Sankyo, Grünenthal, Pierre Fabre, PharmaMar, Samantree, Sysmex und Roche tätig. Er hielt Vorträge für Lilly, Roche, MSD, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Gilead, Grünenthal, AstraZeneca, pfm, Samantree und Eisai, erhielt Reisekosten von Roche und Pfizer und ist im Editorial Board bei medac. S. L. erhielt Honorare bzw. Forschungsunterstützung von Abbvie, AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Roche und Samsung. Weiterhin ist sie beratend tätig für Abbvie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Daiichi Sankyo, Eirgenix, GlaxoSmithKline, Gilead, Lilly, Merck, Novaris, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche und Seagen und ist Mitglied der GBG Forschungs GmbH. H.-C. K. hat Honorare und Reisekostenunterstützung erhalten von Carl Zeiss meditec, Theraclion, Novartis, Amgen, AstraZeneca, Pfizer, Roche, Daiichi Sankyo, Tesaro, MSD, Onkowissen, Eli Lilly, SurgVision, Exact Sciences und Genomic Health und hält Anteile von Theraclion und Phaon Scientific. M. W. hat Honorare erhalten für Vorträge und beratende Tätigkeiten von Pfizer, Roche, Novartis, Lilly, GlaxoSmithKline und AstraZeneca. S. P. erhielt Honorare für beratende Tätigkeiten von Becton & Dickinson, Grünenthal, Sysmex Deutschland, Sysmex Europe, Endomag, pfm medical AG, NeoNavia, NeoDynamics und Triconmed sowie Unterstützungen für Fortbildungen von Roche und für Reisetätigkeiten von Motiva. D. W. hat Honorare für Vorträge und beratende Tätigkeiten von Roche und Pfizer erhalten. M. H. hat Vortragshonorare von Roche und Novartis erhalten. M. U. erhielt Honorare für Vorträge und beratende Tätigkeiten von Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiji Sankyo, Eisai, Gilead, GlaxoSmithKline, Lilly, Molecular Health, MSD Merck, Mundipharma, Mylan, Myriad Genetics, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi Aventis und Saegen. M. B.-P. erhielt Honorare für Vorträge und beratende Tätigkeiten von Roche, Novartis, Pfizer, Eli Lilly, Eisai, GlaxoSmithKline, Seagen, Daiichi Sankyo, pfm medical AG und AstraZeneca, und Studienunterstützung von Exact Sciences. Die AXSANA-Studie wird finanziell von der AGO-B, der Claudia von Schilling Foundation for Breast Cancer Research, der Ehmann-Stiftung Savognin, der AWOgyn, EndoMag, der Merit Medical GmbH und Mammotome unterstützt. Die Sponsoren der Studie hatten weder auf das Protokoll noch auf die Studiendurchführung Einfluss., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Purpose Detection of SARS-CoV-2-infected pregnant women admitted to maternity units during a pandemic is crucial. In addition to the fact that pregnancy is a risk factor for severe COVID-19 and that medical surveillance has to be adjusted in infected women and their offspring, knowledge about infection status can provide the opportunity to protect other patients and healthcare workers against virus transmission. The aim of this prospective observational study was to determine the prevalence of SARS-CoV-2 infection among pregnant women in the hospital setting. Material and Methods All eligible pregnant women admitted to the nine participating hospitals in Franconia, Germany, from 2 June 2020 to 24 January 2021 were included. COVID-19-related symptoms, secondary diseases and pregnancy abnormalities were documented. SARS-CoV-2 RNA was detected by RT-PCR from nasopharyngeal swabs. The prevalence of acute SARS-CoV-2 infection was estimated by correcting the positive rate using the Rogan-Gladen method. The risk of infection for healthcare workers during delivery was estimated using a risk calculator. Results Of 2414 recruited pregnant women, six were newly diagnosed RT-PCR positive for SARS-CoV-2, which yielded a prevalence of SARS-CoV-2 infection of 0.26% (95% CI, 0.10 - 0.57%). Combining active room ventilation and wearing FFP2 masks showed an estimated reduction of risk of infection for healthcare workers in the delivery room to < 1%. Conclusions The prevalence of newly diagnosed SARS-CoV-2 infection during pregnancy in this study is low. Nevertheless, a systematic screening in maternity units during pandemic situations is important to adjust hygienic and medical management. An adequate hygienic setting can minimise the calculated infection risk for medical healthcare workers during patients' labour., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: Patients with metastatic breast cancer (MBC) are treated with a palliative approach with focus on controlling for disease symptoms and maintaining high quality of life. Information on individual needs of patients and their relatives as well as on treatment patterns in clinical routine care for this specific patient group are lacking or are not routinely documented in established Cancer Registries. Thus, we developed a registry concept specifically adapted for these incurable patients comprising primary and secondary data as well as mobile-health (m-health) data., Methods: The concept for patient-centered "Breast cancer care for patients with metastatic disease" (BRE-4-MED) registry was developed and piloted exemplarily in the region of Main-Franconia, a mainly rural region in Germany comprising about 1.3 M inhabitants. The registry concept includes data on diagnosis, therapy, progression, patient-reported outcome measures (PROMs), and needs of family members from several sources of information including routine data from established Cancer Registries in different federal states, treating physicians in hospital as well as in outpatient settings, patients with metastatic breast cancer and their family members. Linkage with routine cancer registry data was performed to collect secondary data on diagnosis, therapy, and progression. Paper and online-based questionnaires were used to assess PROMs. A dedicated mobile application software (APP) was developed to monitor needs, progression, and therapy change of individual patients. Patient's acceptance and feasibility of data collection in clinical routine was assessed within a proof-of-concept study., Results: The concept for the BRE-4-MED registry was developed and piloted between September 2017 and May 2018. In total n = 31 patients were included in the pilot study, n = 22 patients were followed up after 1 month. Record linkage with the Cancer Registries of Bavaria and Baden-Württemberg demonstrated to be feasible. The voluntary APP/online questionnaire was used by n = 7 participants. The feasibility of the registry concept in clinical routine was positively evaluated by the participating hospitals., Conclusion: The concept of the BRE-4-MED registry provides evidence that combinatorial evaluation of PROMs, needs of family members, and raising clinical parameters from primary and secondary data sources as well as m-health applications are feasible and accepted in an incurable cancer collective., Competing Interests: Competing interestsStephanie Stangl reports no disclosures. Kirsten Haas reports no disclosures. Felizitas Eichner reports no disclosures. Anna Grau reports no disclosures. Udo Selig reports no disclosures. Timo Ludwig reports no disclosures. Tanja Fehm reports no disclosures. Tanja Stüber reports no disclosure Asarnusch Rashid reports no disclosures. Alexander Kerscher reports no disclosures. Ralf Bargou reports no disclosures. Silke Hermann reports no disclosures. Volker Arndt reports no disclosures. Martin Meyer reports no disclosures. Manfred Wildner reports no disclosures. Hermann Faller reports no disclosures. Michael G. Schrauder reports no disclosures. Michael Weigel reports no disclosures. Ulrich Schlembach reports no disclosures. Peter U. Heuschmann reports research grants from German Ministry of Research and Education, German Research Foundation, European Union, Charité–Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, University Göttingen (within FIND-AF randomized, supported by an unrestricted research grant to the University Göttingen from Boehringer-Ingelheim), University Hospital Heidelberg (within RASUNOA-prime, supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), grants from Charité–Universitätsmedizin Berlin (within Mondafis, supported by an unrestricted research grant to the Charité from Bayer), outside the submitted work. Achim Wöckel reports grant from German Ministry of Research and Education, received honoraria for consultancy and presentation from Amgen, Novartis, Eisai, Celgene, Pfizer, Tesaro, Aurikamed, TEVA, Lilly, and Roche within the last 5 years., (© The Author(s). 2020.)

Background: Growing demand for risk-reducing surgery in individuals with inherited susceptibility to cancer leads to the question whether these procedures are cost effective for the executing hospitals. This study compared the clinical costs for bilateral risk-reducing mastectomy (BRRM) with and without different types of reconstruction, risk-reducing salpingo-oophorectomy (RRSO), and their combinations with corresponding reimbursements in the statutory health-care system in Germany., Patients and Methods: Real total costs of care for BRRM with and without reconstruction, RRSO, and their combinations were calculated as the sum of all personnel and technical costs. These costs calculated in a German University hospital were compared with the sum of all reimbursements in the German DRG-based health-care system., Results: While sole RRSO, BRRM without reconstruction, and BRRM with secondary DIEP (deep inferior epigastric perforator)-reconstruction still result in a small benefit, we even found shortfalls for the hospital with all other prophylactic operations under consideration. The calculated deficits were especially high for BRRM with implant-based breast reconstruction and for combined operations when the risk reduction is achieved with a minimum of separate operations., Conclusions: Risk-reducing surgery in BRCA-mutation carriers is frequently not cost-covering for the executing hospitals in the German health-care system. Thus, appropriate concepts are required to ensure a nationwide care.

Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10 -5 ). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10 -23 ). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.

Introduction: The care of patients with breast cancer is extremely complex and requires interdisciplinary care in certified facilities. These specialized facilities provide numerous services without being correspondingly remunerated. The question whether breast cancer surgery should be performed in an outpatient setting to reduce costs is increasingly being debated. This study compares inpatient surgical treatment with a model of the same surgery performed on an outpatient basis to examine the potential financial impact., Material and Methods: A theoretical model was developed and the DRG fees for surgical interventions to treat primary breast cancer were calculated. A theoretical 1-day DRG was then calculated to permit comparisons with outpatient procedures. The costs of outpatient surgery were calculated based on the remuneration rates of the AOP (Outpatient Surgery) Contract and the EBM (Uniform Assessment Scale) and compared to the costs of the 1-day DRG., Results: The DRG fee for both breast-conserving surgery and mastectomy is higher than the fee paid in the context of the EBM system, although the same procedures were carried out in both systems. If a hospital were to carry out breast-conserving surgery as an outpatient procedure, the fee would be € 1313.81; depending on the type of surgery, the hospital would therefore only receive between 39.20% and 52.82% of the DRG fee. This was the case even for a 1-day treatment. Compared to the real DRG fees the difference would be even more striking., Conclusion: Carrying out breast cancer surgery as an outpatient procedure would result in a significant shortfall of revenues. Additional services from certified centers, such as the interdisciplinary planning of treatment, psycho-oncological and social-medical care with the involvement of relatives, detailed documentation, etc., which are currently provided without surcharge or adequate remuneration, could no longer be maintained. The quality of processes and excellent results which have been achieved and ultimately the care given by certified facilities would be significantly at risk.

Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.

Purpose: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome., Methods: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated., Results: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival., Conclusions: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.

Background/aim: The aim of this single-arm, prospective, multicenter phase II trial (MiX) was to increase treatment options for women with metastatic breast cancer pretreated with anthracycline and taxane by evaluation of the efficacy and toxicity of the combination of mitomycin C and capecitabine., Patients and Methods: From 03/2004 to 06/2007, a total of 39 patients were recruited and received mitomycin C in combination with capecitabine. The primary end-point was to determinate the tumor response according to Response Evaluation Criteria in Solid Tumors and the rate of toxicities (safety). The secondary study objective was the evaluation of the time to progression (i.e. efficacy)., Results: The median time to progression was 9.3 months (95% confidence interval=6.6-12.0 months) and the median survival was 12.8 months (95% confidence interval=6.8-18.8 months). Most treatment-related adverse events were mild to moderate., Conclusion: Mitomycin C and capecitabine is a good taxane-free option in patients with metastatic breast cancer previously treated with anthracycline., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: No screening programs are available for ovarian or endometrial cancer. One reason for this is the low incidence of the conditions, resulting in low positive predictive values for tests, which are not very specific. One way of addressing this problem might be to use risk factors to define subpopulations with a higher incidence. The aim of this study was to investigate the extent to which a medical history of endometriosis can serve as a risk factor for ovarian or endometrial cancer., Methods: In a hospital-based case-control analysis, the cases represented patients with endometrial or ovarian cancer who were participating in studies aimed at assessing the risk for these diseases. The controls were women between the age of 40 and 85 who were invited to take part via a newspaper advertisement. A total of 289 cases and 1016 controls were included. Using logistic regression models, it was tested whether self-reported endometriosis is a predictor of case-control status in addition to age, body mass index (BMI), number of pregnancies and previous oral contraceptive (OC) use., Results: Endometriosis was reported in 2.1 % of the controls (n = 21) and 4.8 % of the cases (n = 14). Endometriosis was a relevant predictor for case-control status in addition to other predictive factors (OR 2.63; 95 % CI, 1.28 to 5.41)., Conclusion: This case-control study found that self-reported endometriosis may be a risk factor for endometrial or ovarian cancer in women between 40 and 85 years. There have been very few studies addressing this issue, and incorporating it into a clinical prediction model would require a more precise characterization of the risk factor of endometriosis.

Background: Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients' point of view., Methods: The study included 2546 patients (breast cancer 21.6%, gynecological cancer 8.3%, obstetrics 32.7%, endometriosis 7.8%, fertility treatment 3.2%, other benign gynecological illnesses 19.2%, no information for 7.2%) in the outpatient clinic (45.2%) and in the in-patient sector (54.8%) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital's quality management system., Results: As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6%), but only a few were also willing to take part in them (58.4%). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians., Conclusions: The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them.

Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer.

Background: miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists., Methods: We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR., Results: We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 (95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait., Conclusions: Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

Purpose: As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments., Methods: A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation., Results: A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia., Conclusions: Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.