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HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy.The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining.258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC.This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.

Background: Liquid Biopsy (LB) in the form of e.g., circulating tumor cells (CTCs) is a promising non-invasive approach to support current therapeutic cancer management. However, the proof of clinical utility of CTCs in informing therapeutic decision-making for e.g., breast cancer in clinical trials and associated translational research projects is facing the issues of low CTC positivity rates and low CTC numbers – even in the metastasized situation. To compensate for this dilemma, clinical CTC trials are designed as large multicenter endeavors with decentralized sample collection, processing and storage of products, making data management highly important to enable high-quality translational CTC research. Aim: In the DETECT clinical CTC trials we aimed at developing a custom-made, browser-based virtual database to harmonize and organize both decentralized processing and storage of LB specimens and to enable the collection of clinically meaningful LB sample. Methods: ViBiBa processes data from various sources, harmonizes the data and creates an easily searchable multilayered database. Results: An open-source virtual bio-banking web-application termed ViBiBa was created, which automatically processes data from multiple non-standardized sources. These data are automatically checked and merged into one centralized databank and are providing the opportunity to extract clinically relevant patient cohorts and CTC sample collections. Summary: ViBiBa, which is a highly flexible tool that allows for decentralized sample storage of liquid biopsy specimens, facilitates a solution which promotes collaboration in a user-friendly, federalist and highly structured way. The source code is available under the MIT license from https://vibiba.com or https://github.com/asperciesl/ViBiBa

Introduction: The aim of this study was to describe the epidemiology of primary advanced or recurrent endometrial cancer and the outcomes from real-world treatment patterns of patients affected in Germany between 2015 to 2021., Methods: In this retrospective cohort study covering the period from 1 January 2015 to 31 December 2021, data from patients with primary advanced or recurrent endometrial cancer who initiated systemic treatment for their disease were extracted from an anonymized claims dataset. Epidemiologic outcomes were cumulative incidence of endometrial cancer and point prevalence. Overall survival after the index date was assessed, with all-cause death used as an event. Endometrial cancer-related real-world treatment patterns were described for the post-index period., Results: The incidence of primary advanced or recurrent endometrial cancer in 2021 was 4.77 cases/100 000 persons, with no substantial change over time (4.63 in 2018; 4.93 in 2019; 4.45 in 2020). The point prevalence on 1 January 2022 was 0.023%, with a slight increase in prevalence observed from 1 January 2019 onwards. Among 466 patients with confirmed endometrial cancer, the mean (standard deviation) age was 68.0 (11.6) years; the tumor material from 86 patients (18.5%) underwent immunohistochemistry or polymerase chain reaction testing. Median overall survival was estimated to be 47.5 months (95% CI 35.1 to 70.4) and the 5-year survival probability was 46.2%. The most frequent first-line systemic therapies were carboplatin (45.7%) and paclitaxel (43.1%). Second-line therapy was received by 153 patients (32.8%)., Conclusion: The analysis of the German claims data produced contemporary epidemiologic estimates for advanced or recurrent endometrial cancer. Treatments were aligned with guideline recommendations during the study period, with tumor testing yet to enter mainstream practice., (The Author(s). Published by S. Karger AG, Basel.)

Fertility-preserving surgery (FPS) in advanced ovarian cancer (AOC) is extremely rare and consequently, information about the pregnancies of these patients is anecdotal. Therefore, management of the pregnancy after AOC is challenging, especially if an unexpected situation arises. A 31-year-old nulliparous woman was admitted to our tertiary hospital in the 18th week of twin pregnancy with sudden severe abdominal pain. Her medical history included a low-grade AOC stage IIIc diagnosed 2 years before pregnancy and treated by debulking FPS and systemic therapy with carboplatin/paclitaxel and bevacizumab. Clinical examination described normal vital signs and peritoneal irritation without any vaginal discharge. Sonography revealed free fluid in the pouch of Douglas and intact twin pregnancy. Laboratory work showed elevated leukocytes with neutrophilia. To evaluate appendicitis magnetic resonance imaging of the abdomen was indicated. This revealed a uterine rupture with the now extra-cavitary position of the twins. Simultaneously, the patient's symptoms deteriorated, and emergency surgery was necessary where hemoperitoneum with avital fetuses were present. Despite excessive blood loss the uterus could be repaired and preserved. Previous resection of the uterine serosa during her debulking FPS, administration of bevacizumab affecting smooth muscles, and overstretching the uterus in the twin pregnancy were considered as possible risk factors for the presenting uterine rupture. Pregnancy after AOC is possible but should be monitored closely, especially due to the hidden long-term consequences of its therapy. In the differential diagnosis of sudden abdominal pain during pregnancy uterine rupture should be considered even in patients with an unscared uterus., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Introduction: The third-generation antibody-drug conjugates (ADC), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), recently obtained approval for metastatic breast cancer treatment across various subtypes and therapeutic contexts., Materials and Methods: This retrospective, multicentric study evaluated real-world tolerability, feasibility and efficacy in a pre-treated, real-world cohort at three major German breast cancer centers., Results: 125 patients treated with T-DXd or SG from November 2020 to June 2023 were included (T-DXd: 77 patients; SG: 48 patients). The median treatment duration was 6.0 months for T-DXd and 3.5 months for SG therapy, with a median follow-up duration of 10.4 months for T-DXd (95% CI: 8.4-11.6) and 11.8 months for SG (95% CI: 8.0-14.4). Severe neutropenia (CTC ≥ III°) occurred in 33.3% during SG therapy, with a numerical reduction observed following primary, prophylactic use of G-CSF. T-DXd-associated pneumonitis occurred in 8 out of 77 patients (10.4 %). Median progression-free survival (mPFS) was 8.6 months (95% CI: 5.8-12.4) with T-DXd (HER2+: 10.8; HER2-low: 4.7) and 4.9 months (95% CI: 2.8-6.3) with SG (TNBC 4.9; HR+/HER2-: not reached). Median overall survival (OS) was 23.8 months (95% CI: 16.1-not estimable) with T-DXd (HER2+: 27.1; HER2-low: not reached), and 12.4 months (95% CI: 8.7-not estimable) with SG therapy (TNBC: 12.4, HR+/HER2-: not reached). 95.7% of the protocol-specified, therapeutic dose was administered for T-DXd and 89.6% for SG., Conclusion: Overall, this indicates good feasibility, tolerability, and effectiveness of ADC therapies in the real-world setting., Competing Interests: Conflict of Interest H. Schäffler: Travel Support by Daiichi Sankyo and Gilead, Honoraria by Novartis; D. Jakob: none; S. Huesmann: none; K. Pfister: Honoraria by Pfizer Novartis and Gilead; K. Veselinovic: Honoraria by Roche, Pfizer, AstraZeneca; F. Schochter: Travel Support, Honoraria and Consulting Fees by AstraZeneca, Roche, Karyopharm, Merck, GlaxoSmithKline, Eisai, Clovis; E. Leinert: none; V. Fink: none; B. Rack: Honoraria and research funding by AstraZeneca and Novartis; A. Englisch: none; L. Volmer: none; T. Engler: Travel Support, Honoraria and Consulting Fees by AstraZeneca, GSK, Gilead, Novartis, Lilly, Pfizer, MSD, Pierre Fabre, Stemline, Roche, Daiichi Sankyo; ML. Frevert: Honoraria by Novartis; I. Juhasz-Böss: none; S. Brucker: Travel Support and Consulting Fees by Hologic, Sanofi, AstraZeneca, Lilly, MSD, Medtronic, Pfizer; S. Heublein: research funding and honoraria from Clovis Oncology, Inc., GlaxoSmithKline, Novartis, Roche, AstraZeneca and Pfizer. Participation in advisory boards for Novartis, GlaxoSmithKline, and Merck Sharp & Dohme Corporation; W. Janni: Travel Support, Honoraria and Consulting Fees by Daiichi Sankyo, AstraZeneca, Gilead; FA. Taran: Travel Support by Gilead, Consulting Fees by AstraZeneca, Gilead, MSD, ImmunoGen, Onkowissen, Roche, GSK; A. Hartkopf: Travel Support by Daiichi Sankyo, Gilead, Roche, AstraZeneca, Pfizer, Honoraria by Daiichi Sankyo, Gilead, Seagen, Roche, AstraZeneca, Pfizer, Lilly, MSD, Novartis; D. Dannehl: Travel Support by Gilead and Daiichi Sankyo, Honoraria by Gilead., (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 commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background The preparation of multidisciplinary team (MDT) meetings can be time-consuming. In addition to the clinical data being available digitally in subsystems, the preparation of more complex cases requires literature research. Several expert systems have been developed to support this process. However, the interaction with these systems has to be trained. Current development enables linguistic interaction with such artificial intelligence (AI) systems. To the best of our knowledge, these have not been tested as premedical screening tools for MDT. Methods This is a retrospective consecutive case series of 10 cervical cancer cases comparing the medical recommendations of the MDT and artificial intelligence (AI) on a low level (i.e., surgery, systemic treatment, and radiotherapy). Results The clinical cases ranged from primary diagnosis via suspected recurrence to palliative settings. The AI repeatedly stated that medical professionals need to be consulted before treatment decisions. The AI answers ranged from no agreement to overachievement by mentioning treatment options for preexisting risk factors (such as obesity). In standard cases, the AI answer matched well with the expert recommendations. In some cases, the AI answers were contrary to our treatment recommendation. Conclusion The interaction with current language AIs is temptingly easy, and the replies are very understandable. Despite the AI warning regarding medical recommendations in the majority of our cases, there was a good match with the MDT recommendations. However, in some cases, the medical evidence behind the answers was missing or in the worst case fictional. In our case series, the AI did not meet the requirements to support a clinical MDT meeting by prescreening the therapeutic options. However, it did exceed the expectations regarding the risk factors of the patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ebner et al.)

Objective: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy., Methods: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints. Safety and tolerability were also assessed., Results: Of the 263 patients enrolled in the SIENDO trial, 113 patients had TP53wt EC; 70/113 (61.9%) had TP53wt/proficient mismatch repair (pMMR) EC, and 29/113 (25.7%) had TP53wt/deficient mismatch repair (dMMR) EC. As of April 1, 2024, the median PFS (mPFS) for TP53wt patients who received selinexor compared with placebo was 28.4 versus 5.2 months (36.8-month follow-up, HR 0.44; 95% CI 0.27-0.73). A benefit in mPFS was seen with selinexor versus placebo regardless of MMR status (patients with TP53wt/pMMR EC: 39.5 vs 4.9 months, HR 0.36; 95% CI 0.19-0.71; patients with TP53wt/dMMR EC: 13.1 vs 3.7 months, HR 0.49; 95% CI 0.18-1.34). Selinexor treatment was generally manageable, with no new safety signals identified., Conclusion: In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

With more novel drugs being approved for the treatment of ovarian carcinoma, the question remains to what extent patients benefit from antiangiogenic treatment with bevacizumab, either in combination with poly-(ADP-ribose) polymerase inhibitors or as single-agent maintenance. As fibroblast growth factor receptors and their ligands (FGFRs/FGFs) are key players in angiogenic signaling and have been linked to resistance to several drugs, we investigated the prognostic or predictive potential of FGFs/FGFRs signaling in the context of bevacizumab treatment within the prospective phase III AGO-OVAR11/ICON-7 study. FGFR1, FGFR2, FGFR3, FGFR4, FGF1, and FGF19 gene expressions were determined in 380 ovarian carcinoma tumor samples collected from German centers in the multicenter phase III AGO-OVAR11 trial/ICON-7 trial. All patients received carboplatin and paclitaxel, administered every 3 weeks for 6 cycles, and were randomized to bevacizumab. Expressions of FGFR1, FGFR2, FGF1, and FGF19 were associated with progression-free survival in both uni- and multivariate (FGFR1: HR, 1.6, P < .001; FGFR2: HR, 1.6, P = .002; FGF1: HR, 2.3, P < .001; and FGF19: HR, 0.7; P = .007) analysis. A signature built by FGFR1, FGFR4, and FGF19 defined a subgroup (n = 62) of patients that derived the greatest bevacizumab-associated improvement of progression-free survival (HR, 0.3; P = .004). In this exploratory analysis of a prospective randomized phase III trial, we provide evidence that the expression of FGFRs/FGFs might have independent prognostic values. An FGFR/FGF-based gene signature identified in our study appears to predict long-term benefit from bevacizumab. This observation is hypothesis-generating and requires validation on independent cohorts., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC., Patients and Methods: ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries. Patients 18 years or older with histologically confirmed EC were enrolled. All had completed a single line of at least 12 weeks of taxane-platinum combination chemotherapy and achieved partial or complete response. Patients were assigned to receive 80 mg oral selinexor once weekly or placebo with 2:1 random assignment (ClinicalTrials.gov identifier: NCT03555422)., Results: Between January 2018 and December 2021, 263 patients were randomly assigned, with 174 allocated to selinexor and 89 to placebo. The median PFS was 5.7 months (95% CI, 3.81 to 9.20) with selinexor versus 3.8 months (95% CI, 3.68 to 7.39) with placebo (hazard ratio [HR], 0.76 [95% CI, 0.54 to 1.08]; two-sided P = .126), which did not meet the criteria for statistical significance in the intent-to-treat population. Incorrect chemotherapy response stratification data for 7 (2.7%) patients were identified. In a prespecified exploratory analysis of PFS in audited stratification data, PFS for selinexor met the threshold for statistical significance (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Furthermore, patients with the TP53 wild-type (wt) EC had a median PFS of 13.7 and 3.7 months with selinexor and placebo. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%)., Conclusion: The significance level for PFS was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53 wt EC showed promising results with selinexor maintenance therapy.

Adnexal masses affect 2-10% of all pregnancies. The highest incidence of 1-6% can be seen in the first trimester, with a high rate of spontaneous remission. Two percent of these masses are malignant neoplasms or borderline tumors. A rare benign mass of the adnexa in pregnancy is hyperreactio luteinalis characterised by bilateral, multicystic ovaries with a frequent occurrence in the 3 rd trimester. Clinical signs include maternal hyperandrogenaemia with virilisation, hyperemesis, nonspecific abdominal pain or laboratory findings of hyperthyroidism and elevated ß-HCG. Hyperreactio luteinalis does not require therapy due to complete spontaneous remission postpartum, but is often treated surgically in graviditate. In our case we report a first-time gravida in the 31 st week of pregnancy with a symptomatic 25-cm multicystic, partly solid mass. After antenatal corticosteroid therapy, an exploratory laparotomy with right adnexectomy was performed on suspicion of malignancy. Histology revealed a hyperreactio luteinalis with an incidental finding of a serous borderline tumor of the ovary (FIGO IIIB). At 33 weeks of gestation, a pathological CTG was observed, and an urgent secondary caesarean section by re-longitudinal laparotomy was performed. Postpartum completion surgery revealed no further neoplastic cells., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Obesity and the presence of circulating tumor cells (CTCs) before and/or after chemotherapy are associated with poor outcome in breast cancer (BC) patients. The activation of oncogenic pathways in fatty tissue leads to cell proliferation, suggesting a possible link between obesity and CTCs., Materials and Methods: In the phase III SUCCESS A trial, 3754 patients with early BC were randomized to 3 cycles of fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel with or without gemcitabine. Data of 1088 patients with CTC assessments (CellSearch-System; Menarini Silicon Biosystems, Italy) and body mass index (BMI) measurements both before and after chemotherapy were available. Patients were classified according to the WHO's international definitions as underweight, normal weight, overweight, or obese, and according to their weight-change during chemotherapy into a weight-loss group (> 5% decrease), stable-weight group (≤ 5% weight-change) or weight-gain group (>5% increase). Associations between CTC positivity and, BMI or weight-change group were analyzed using frequency-table methods., Results: At study entry, 47.4% patients were underweight or normal weight, 33.6% were overweight and 18.9% were obese. Before and after chemotherapy, CTCs were detected in 20.1% and 22.6% of patients, respectively. There was no association between CTC positivity and BMI before (P = 0.104) or after (P = 0.051) chemotherapy. Furthermore, there was no association between weight-change group and CTC status before/after chemotherapy (P = 0.332)., Conclusions: According to our analysis, the risk factors obesity and prevalence of CTCs are not associated and may represent independent prognostic factors., Competing Interests: Disclosure TWP: Personal fees from Lilly and Novartis. FS: Grants from AstraZeneca, Roche and Karyopharm. Personal fees from Roche, Pfizer, Novartis, AstraZeneca, GSK, MSD, Clovis and Eisai. TF: Personal fees from Medconcept, Onkowissen. KP: Grants from: EU/IMI CANCER-ID EFPIA, Personal fees from: BMS, Agena, Menarini, Novartis, Sanofi, Illumina, Abcam, MSD, Boehringer Ingelheim, Eppendorf and Hummingbird. AS: Grants from Celgene, Roche and AbbVie. Personal fees from Celgene, Roche, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen and Pierre Fabre. HT: Personal fees from Novartis, Roche, GSK, Seagan, Pfizer, Lilly, Astra Zeneca, Daiichi, Exact Science, Vifor and Seagan. Shares/stocks from CHOP GmbH, VISION MED GmbH, Care and Coach GmbH, Onco Medical Consult GmbH. VA-F: Honoraria from Novartis. PF: Grants from Pfizer, Cepheid and Biontech. Personal fees from Novartis Daiichi-Sankyo, Pfizer Astra Zeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, SeaGen, Roche, Agendia, Sanofi Aventis, Gilead, Mylan and Menarini., WJ: honoraria from Sanofi-Aventis, Novartis and Pfizer. BR: honoraria from AstraZeneca, Chugai, Lilly, Novartis, Sanofi-Aventis, and Jannssen-Cilag. All other authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Approximately 6% of women with breast cancer carry pathogenic germline variants in predisposition genes such as BRCA1 and BRCA2. Depending on personal and family cancer history, it is therefore recommended to test for hereditary breast cancer. Moreover, as shown by the phase III OlympiA trial, olaparib significantly improves overall survival in patients with HER2 negative (HER2-) early breast cancer who (1) carry a BRCA1 or BRCA2 germline mutation (gBRCA1/2-positive), (2) have received (neo)adjuvant chemotherapy and (3) are at high clinical risk. The objective of the current analysis was to determine the number of patients with early HER2- breast cancer who are at high clinical risk, according to the inclusion criteria of OlympiA, and to estimate how many of these patients would meet the criteria for hereditary cancer testing in a real-world analysis., Methods: All patients included in this retrospective analysis were treated for early breast cancer (eBC) at the Department of Gynecology and Obstetrics, Ulm University Hospital, Germany, and the Department of Women's Health at Tuebingen University Hospital, Germany, between January 2018 and December 2020. Patients were identified as high risk, in line with the clinicopathological determiners used in the OlympiA trial. The criteria of the German Consortium for Hereditary Breast and Ovarian Cancer were used to identify patients who qualify for hereditary cancer testing., Results: Of 2384 eligible patients, 1738 patients (72.9%) showed a hormone receptor positive (HR+)/HER2- tumor biology, 345 patients (14.5%) displayed HER2+ breast cancer and 301 patients (12.6%) suffered from HR-/HER2- breast cancer (TNBC). Of 2039 HER2- breast cancer patients, 271 patients (13.3%) were at high clinical risk. This cohort encompassed 130 of the 1738 patients with HR+/HER2- breast cancer (7.5%) and 141 of 301 patients with TNBC (46.8%). A total of 121 of 271 patients (44.6%) with high clinical risk met the criteria for hereditary cancer testing (34 of 130 (26.2%) HR+/HER2- patients and 87 of 141 (61.7%) patients with TNBC)., Conclusion: Approximately one in ten patients with HR+/HER2-, and half of the patients with TNBC, meet the high-risk criteria according to OlympiA. Half of these patients do not meet the criteria for hereditary cancer testing and should therefore be tested for the presence of gBRCA1/2 mutations, irrespective of their own or family cancer history. The overall number of patients with early breast cancer benefiting from olaparib needs to be investigated in future studies.

Purpose: Perioperative cognitive dysfunction can be observed in all age groups of patients. Sometimes, this is more stressful to the patient than the actual surgical wound. Enhanced recovery after surgery pathways screen for patients at risk and lead to early post-surgical intervention. To prevent cognitive dysfunction, a prehabilitation approach might be useful., Methods: This systematic literature review provides an overview on the current knowledge on prehabilitation for cognitive dysfunction for gynaecological patients by searching the National Library of Medicine (PubMed) in February 2020 to identify publications regarding presurgical cognitive training with three different search terms., Results: 501 articles were identified and after screening for eligibility five were left for further analysis. Generally, cognitive function is split into several cognitive aspects like anxiety or memory, speed, attention, flexibility or problem-solving functions. Each of these aspects can/need to be trained to show an improvement after general anaesthesia. Training possibilities range from relaxation methods via music, one-on-one personal training sessions to electronically supported training units., Conclusion: Prehabilitation of the cognitive function can be split in different cognitive domains. Each of these domains seem to be influenced by training. The training itself can be based on applications or known relaxation methods or even old-fashioned board games. The evidence is, however, still low and there is a need for further studies., (© 2021. The Author(s).)

Background: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2)., Method: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance., Results: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10 -6 ) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted., Conclusion: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The prognostic relevance of circulating tumor cells (CTCs) in breast cancer is well established. However, little is known about the association of CTCs and site of first metastasis. In the SUCCESS A trial, 373 out of 3754 randomized high-risk breast cancer patients developed metastatic disease. CTC status was assessed by the FDA-approved CellSearch ® -System (Menarini Silicon Biosystems, Bologna, Italy) in 206 of these patients before chemotherapy and additionally in 159 patients after chemotherapy. CTCs were detected in 70 (34.0%) of 206 patients before (median 2 CTCs, 1-827) and in 44 (27.7%) of 159 patients after chemotherapy (median 1 CTC, 1-124); 16 (10.1%) of 159 patients were CTC-positive at both timepoints. The site of first distant disease was bone-only, visceral-only, and other-site-only in 44 (21.4%), 60 (29.1%), and 74 (35.9%) patients, respectively, while 28 (13.6%) patients had multiple sites of first metastatic disease. Patients with CTCs at both timepoints more often showed bone-only first distant disease (37.5% vs. 21.0%) and first distant disease at multiple sites (31.3% vs. 12.6%) than patients without CTCs before and/or after chemotherapy ( p = 0.027). In conclusion, the presence of CTCs before and after chemotherapy is associated with multiple-site or bone-only first-distant disease and may trigger intensified follow-up and perhaps further treatment.

Soluble MUC1 has been discussed as a biomarker for predicting prognosis, treatment efficacy, and monitoring disease activity in breast cancer (BC) patients. Most studies in adjuvant settings have used preoperative assessment. This study, part of the SUCCESS-A trial (NCT02181101), assessed the prognostic value of soluble MUC1 before and after standard adjuvant chemotherapy. Patients with high-risk BC were treated within the SUCCESS-A trial with either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel or three cycles of FEC followed by three cycles of docetaxel and gemcitabine. Cox regression analyses were performed to investigate the prognostic value of CA27.29 before and after chemotherapy relative to disease-free survival (DFS), along with established BC prognostic factors such as age, body mass index, tumor size, nodal status, estrogen receptor, progesterone receptor, HER2 status, and grading. Pre-chemotherapy and post-chemotherapy CA27.29 assessments were available for 2687 patients of 3754 randomized patients. Pre-chemotherapy CA27.29 assessment was associated with DFS in addition to established prognostic factors. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy CA27.29 assessment.

Circulating tumor cells (CTCs) traverse vessels to travel from the primary tumor to distant organs where they adhere, transmigrate, and seed metastases. To cope with these challenges, CTCs have reached maximal flexibility to change their differentiation status, morphology, migratory capacity, and their responses to genotoxic stress caused by metabolic changes, hormones, the inflammatory environment, or cytostatic treatment. A significant percentage of breast cancer cells are defective in homologous recombination repair and other mechanisms that protect the integrity of the replication fork. To prevent cell death caused by broken forks, alternative, mutagenic repair, and bypass pathways are engaged but these increase genomic instability. CTCs, arising from such breast tumors, are endowed with an even larger toolbox of escape mechanisms that can be switched on and off at different stages during their journey according to the stress stimulus. Accumulating evidence suggests that DNA damage responses, DNA repair, and replication are integral parts of a regulatory network orchestrating the plasticity of stemness features and transitions between epithelial and mesenchymal states in CTCs. This review summarizes the published information on these regulatory circuits of relevance for the design of biomarkers reflecting CTC functions in real-time to monitor therapeutic responses and detect evolving chemoresistance mechanisms.

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

Background: Liquid Biopsy (LB) in the form of e.g., circulating tumor cells (CTCs) is a promising non-invasive approach to support current therapeutic cancer management. However, the proof of clinical utility of CTCs in informing therapeutic decision-making for e.g., breast cancer in clinical trials and associated translational research projects is facing the issues of low CTC positivity rates and low CTC numbers - even in the metastasized situation. To compensate for this dilemma, clinical CTC trials are designed as large multicenter endeavors with decentralized sample collection, processing and storage of products, making data management highly important to enable high-quality translational CTC research., Aim: In the DETECT clinical CTC trials we aimed at developing a custom-made, browser-based virtual database to harmonize and organize both decentralized processing and storage of LB specimens and to enable the collection of clinically meaningful LB sample., Methods: ViBiBa processes data from various sources, harmonizes the data and creates an easily searchable multilayered database., Results: An open-source virtual bio-banking web-application termed ViBiBa was created, which automatically processes data from multiple non-standardized sources. These data are automatically checked and merged into one centralized databank and are providing the opportunity to extract clinically relevant patient cohorts and CTC sample collections., Summary: ViBiBa, which is a highly flexible tool that allows for decentralized sample storage of liquid biopsy specimens, facilitates a solution which promotes collaboration in a user-friendly, federalist and highly structured way. The source code is available under the MIT license from https://vibiba.com or https://github.com/asperciesl/ViBiBa., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment., Methods: In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models., Results: There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (β 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (β - 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (β -0.34, p 0.03) and by immigrants (β -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (β 0.19/0.19/0.20/0.25; each p < 0.01)., Conclusion: Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.

Evidence suggests that the DNA end-binding protein p53-binding protein 1 (53BP1) is down-regulated in subsets of breast cancer. Circulating tumor cells (CTCs) provide accessible "biopsy material" to track cell traits and functions and their alterations during treatment. Here, we prospectively monitored the 53BP1 status in CTCs from 67 metastatic breast cancer (MBC) patients with HER2- CTCs and known hormone receptor (HR) status of the primary tumor and/or metastases before, during, and at the end of chemotherapeutic treatment with Eribulin. Nuclear 53BP1 staining and genomic integrity were evaluated by immunocytochemical and whole-genome-amplification-based polymerase chain reaction (PCR) analysis, respectively. Comparative analysis of CTCs from patients with triple-negative and HR+ tumors revealed elevated 53BP1 levels in CTCs from patients with HR+ metastases, particularly following chemotherapeutic treatment. Differences in nuclear 53BP1 signals did not correlate with genomic integrity in CTCs at baseline or with nuclear γH2AX signals in MBC cell lines, indicating that 53BP1 detected features beyond DNA damage. Kaplan-Meier analysis revealed an increasing association between nuclear 53BP1-positivity and progression-free survival (PFS) during chemotherapy until the final visit. Our data suggest that 53BP1 detection in CTCs could be a useful marker to capture dynamic changes of chemotherapeutic responsiveness in triple-negative and HR+ MBC.

Mutations in the ligand-binding domain (LBD) of the ESR1 gene result in resistance to estrogen deprivation therapy (EDT) in breast cancer. Their detection might enable optimization of therapy strategies. However, the predictive utility of the primary tumor (PT) is limited, and obtaining serial biopsies of metastatic lesions is challenging. To underline their application as a liquid biopsy, single circulating tumor cells (CTCs) were analyzed with a next-generation sequencing approach for the ESR1 coding region. CTCs from 46 metastatic luminal breast cancer patients were enriched using CellSearch system and isolated by micromanipulation. Their genomic DNA was amplified and the ESR1 gene was sequenced. Furthermore, tissue samples from corresponding PTs and/or metastatic lesions were investigated. ESR1 mutations were detected in 12 patients-exclusively in patients treated with EDT (P = 0.048). In seven cases mutations were located in the hotspot regions in the LBD. Six novel mutations were identified. ESR1 mutations were absent in PT tissue samples and were detected only in metastases obtained after CTC characterization. Single-cell CTC analysis for ESR1 mutations could be of clinical value to identify patients who progress under EDT and therefore benefit from an early switch to an alternative endocrine therapy or other treatment regimens. Furthermore, our data indicate that mutations outside the LBD's hotspot regions might also contribute to resistance to EDT., (Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

In recent years, breast cancer treatment has become increasingly individualized. Circulating tumor cells (CTCs) have the potential to move personalized medicine another step forward. The prognostic relevance of CTCs has already been proven both in early and metastatic breast cancer. In addition, there is evidence that changes in CTC numbers during the course of therapy can predict treatment response. Thus, CTCs are a suitable tool for repeated treatment monitoring through noninvasive liquid biopsy. The next step is to evaluate how this information can be used for clinical decision making with regard to the extension, modification, or abandonment of a treatment regimen. This review will summarize the completed and ongoing clinical trials using CTC number or phenotype for treatment decisions. Based on current knowledge, CTCs can be regarded as a useful prognostic and predictive marker that is well suited for both risk stratification and treatment monitoring in breast cancer patients. However, there is still the need to provide sufficient and unequivocal evidence for whether CTCs may indeed be used to guide treatment decisions in everyday clinical practice. The results of the ongoing trials described in this review are eagerly awaited to answer these important questions., Competing Interests: Dr. Schochter: honoraria by Roche, Novartis and Pfizer; Dr. Friedl: honoraria by Novartis; Dr. deGregorio: honoraria from Roche, Pfizer, Novartis, Celgene, Tesaro, Daiichi; Dr. Krause: no relevant financial relationsships; Prof. Huober: research grants from Celgene, Novartis; Speaker fees by Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene, Eisai; consultant by Lilly, Novartis, Roche, Pfizer, Hexal, AstraZeneca, MSD, Celgene; Travel expenses by Roche, Pfizer, Novartis, Celgene, Daiichi; Prof Rack: research grants and honoraria Aventis, Pharmacia, Amgen, Novartis, AstraZenica, Roche, Pfizer, Chugai; Prof. Janni has received research grants and honoraria from Menarini Silicon Biosystems, Johnson&Johnson. Institutional founding by the Deutsche Krebshilfe (German Cancer Aid), Menarini Silicon Biosystems, Roche, Novartis, GlaxoSmithKline, Amgen, Celgene, Eisai, and TEVA.

Background: Medical education is evolving from "learning by doing" to simulation-based hands-on tutorials., Objective: The aim of this prospective 2-armed study was to evaluate a newly developed augmented reality ultrasound app and its effect on educational training and diagnostic accuracy., Methods: We recruited 66 medical students and, using imaging and measuring a kidney as quality indicators, tested them on the time they needed for these tasks. Both groups used textbooks as preparation; in addition, the study group had access to a virtual ultrasound simulation app for mobile devices., Results: There was no significant difference between the study arms regarding age (P=.97), sex (P=.14), and previous ultrasound experience (P=.66). The time needed to complete the kidney measurements also did not differ significantly (P=.26). However, the results of the longitudinal kidney measurements differed significantly between the study and control groups, with larger, more realistic values in the study group (right kidney: study group median 105.3 mm, range 86.1-127.1 mm, control group median 92 mm, range 50.4-112.2 mm; P<.001; left kidney: study group median 100.3 mm, range 81.7-118.6 mm, control group median 85.3 mm, range 48.3-113.4 mm; P<.001). Furthermore, whereas all students of the study group obtained valid measurements, students of the control group did not obtain valid measurements of 1 or both kidneys in 7 cases., Conclusions: The newly developed augmented reality ultrasound simulator mobile app provides a useful add-on for ultrasound education and training. Our results indicate that medical students' use of the mobile app for training purposes improved the quality of kidney measurements., (©Florian Ebner, Amelie De Gregorio, Fabienne Schochter, Inga Bekes, Wolfgang Janni, Krisztian Lato. Originally published in JMIR Serious Games (http://games.jmir.org), 01.05.2019.)

Objectives: In breast cancer, large tumor size, positive nodal stage and a triple-negative tumor subtype are associated with reduced survival, but the interactions between these prognostic factors are not well understood., Material and Methods: Here we re-evaluated the impact of tumor size, nodal stage and tumor subtype on disease-free survival (DFS), overall survival (OS), distant disease-free survival (DDFS) and breast cancer specific survival (BCSS) in a retrospective analysis using data from the adjuvant SUCCESS A trial. Subgroup analyses were conducted to assess whether the effect of tumor size and nodal stage on survival depended on tumor subtype., Results: Increasing tumor size, higher nodal stage and triple negative breast cancer (TNBC) were associated with unfavorable prognosis (all p < 0.001). There was no significant interaction between tumor subtype and tumor size (p > 0.5 for all four survival endpoints), but we found significant interactions between tumor subtype and nodal stage (p < 0.05 for all four survival endpoints), with no differences in survival among tumor subtypes for patients with pN0 tumors (all p > 0.05) and pronounced differences in survival among tumor subtypes for patients with positive nodal stage (all p < 0.001)., Conclusions: This analysis confirms tumor size, nodal stage and tumor subtype as independent prognostic factors in high-risk early breast cancer. Nodal-positive patients with TNBC had a considerably worse outcome compared to nodal-positive patients with another tumor subtype. This underlines the importance for early detection particularly for patients with TNBC., Trial Registration: EudraCT 2005-000490-21; ClinicalTrials.gov Identifier: NCT02181101., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Several studies have provided evidence on the prognostic relevance of circulating tumor cells (CTCs) detected before and after chemotherapy regarding overall survival (OS) and progression-free survival (PFS) in early breast cancer (EBC). We provide data on the prevalence of CTCs 2 and 5 years after primary diagnosis in a cohort of patients with EBC., Methods: The SUCCESS study is a multicenter, prospective, randomized trial comparing PFS in primary breast cancer patients undergoing one of two adjuvant chemotherapy regimens followed by 2 versus 5 years of treatment with zoledronate. CTCs from patients without signs of breast cancer recurrence were analyzed in peripheral blood using the FDA cleared CellSearch® System (Veridex, USA) 2 and 5 years after primary diagnosis., Results: CTCs were detected at 2 and 5 years after primary diagnosis in 96 (16.7%) and 47 (8.2%) of the 574 patients, respectively. There were no associations between CTC status and patient and tumor characteristics or treatment regimens. In 442 (77.0%) patients, no CTCs were detected at either of the two time points, and in 11 patients (1.9%), CTCs were found at both 2 and 5 years after primary diagnosis. In 85 (14.8%) patients, CTCs were present 2 years after primary diagnosis but not after 5 years, while 36 (6.3%) patients had CTCs in their blood only at the 5-year follow-up., Conclusions: In patients with EBC, CTCs can be detected even 5 years after primary diagnosis without clinical signs of disease recurrence.

Background: Little is known about the effect of granulocyte colony-stimulating factor (G-CSF) treatment during adjuvant chemotherapy on prognostic markers. The present study explored the association between G-CSF and changes in cancer antigen (CA)27.29 and circulating tumor cell (CTC) levels during therapy., Patients and Methods: A total of 3754 node-positive or high-risk node-negative early-stage breast cancer patients were treated within the SUCCESS-A trial (simultaneous study of gemcitabine-docetaxel combination adjuvant treatment, as well as extended bisphosphonate and surveillance-trial). CA27.29 and CTCs were determined before the start and within 6 weeks after the end of chemotherapy., Results: Overall, 1324 of the 2646 patients (50.0%) available for analysis had ≥ 1 G-CSF applications during chemotherapy. G-CSF application was significantly associated with CA27.29 status before and after chemotherapy (χ 2  = 30.6, df = 3; P < .001), because 238 patients (18.0%) with G-CSF treatment but only 146 (11.0%) without G-CSF treatment switched from a negative CA27.29 status before to a positive CA27.29 status after chemotherapy. In addition, patients with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy compared with patients without any G-CSF application during chemotherapy (Mann-Whitney U test; Z = -7.81, P < .001). No significant association was found between G-CSF application and CTC status before or after chemotherapy (χ 2  = 1.2, df = 3; P = .75)., Conclusion: Cautious interpretation is needed regarding elevated levels of MUC-1-derived tumor markers such as CA27.29 shortly after adjuvant chemotherapy when G-CSF has been given, because G-CSF treatment was associated with increased CA27.29 levels after chemotherapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In addition to established prognostic factors, individual lifestyle-associated factors, such as obesity, physical activity, and diet, seem to modulate the course of breast cancer. The aim of this analysis was to evaluate the influence of weight changes during adjuvant chemotherapy on outcome in a large multicenter prospectively randomized trial., Patients and Methods: The ADEBAR trial compares a sequential chemotherapy consisting of epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5-fluorouracil/cyclophosphamide regimen in patients with lymph node-positive early breast cancer. Body weight was measured before each cycle of chemotherapy. According to the relative weight change (≥ 5%) between the first and the last cycle, patients were categorized into the weight gain, weight loss, or stable weight group. Overall survival (OS) and disease-free survival were assessed by univariate Kaplan-Meier and multivariate Cox regression analyses., Results: Concise data from 1080 of 1493 participants who completed all cycles of chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight changed by ≥ 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight. Multivariate analysis showed a significant independent effect of weight change on OS (P = .039), but not on disease-free survival (P = .111). Both weight change groups had a worse OS compared to patients with stable weight (weight gain: hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss: hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067)., Conclusion: Weight change of > 5% during adjuvant chemotherapy in patients with high-risk early breast cancer is associated with poor OS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Optimal choice and sequence of endocrine treatment following adjuvant chemotherapy in postmenopausal early breast cancer patients are still under discussion and treatment stratification factors are missing., Patients and Methods: Postmenopausal women with HER2-negative, hormone receptor-positive tumors and persisting circulating tumor cells (CTCs; assessed using the FDA-approved CellSearch® System, Janssen Diagnostics, LLC) after chemotherapy were randomized to 2 years of tamoxifen followed by 3 years of exemestane (tamoxifen-exemestane group, n = 54) or 5 years of exemestane (exemestane-only group, n = 54). CTCs were again assessed after the first 2 years of endocrine treatment. In addition, safety data were compared between the 2 groups., Results: The 2 groups were well-balanced with regard to baseline characteristics. The CTC clearance rate after 2 years was 89% in the exemestane-only group and 97% in the tamoxifen-exemestane group (exact Fisher test, p = 0.36). The safety profile showed good tolerability with few grade 3 or 4 adverse events in both groups., Conclusion: The similar CTC clearance rate after 2 years of endocrine therapy with exemestane or tamoxifen, and the safety profiles obtained may indicate comparable efficacy and tolerability of both endocrine treatment regimens. However, these results have to be confirmed by final survival and safety analysis., (© 2018 S. Karger GmbH, Freiburg.)

Dissemination of tumour cells and the development of solid metastases occurs via blood vessels and lymphatics. Circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) can be detected in venous blood in patients with early and metastatic breast cancer, and their prognostic relevance has been demonstrated on numerous occasions. Repeated testing for CTCs and ctDNA, or regular so-called "liquid biopsy", can be performed easily at any stage during the course of disease. Additional molecular analysis allows definition of tumour characteristics and heterogeneity that may be associated with treatment resistance. This in turn makes personalised, targeted treatments possible that may achieve both improved overall survival and quality of life.

Background: Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment., Methods: The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics)., Results: Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18)., Conclusions: The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: HER2 is one of the predominant therapeutic targets in breast cancer. The metastatic selection process may lead to discrepancies between the HER2 status of the primary tumor and circulating tumor cells (CTCs). This study analyzed the HER2 status of CTCs in patients with HER2-positive primary breast cancer at the time of diagnosis. Aim of the study was to assess potential discordance of HER2 status between primary tumor and CTCs, as this may have important implications for the use of HER2-targeted therapy., Methods: The number and HER2 status of CTCs out of 30ml peripheral blood were assessed in 642 patients using the CellSearch System (Janssen Diagnostics, USA). The cutoff for CTC positivity was the presence of at least 1 CTC, and the cutoff for HER2 positivity of CTCs was the presence of at least 1 CTC with a strong HER2 staining., Results: 258 (40.2%) of the 642 patients were positive for CTCs (median 2; range 1-1,689). 149 (57.8%) of these 258 patients had at least 1 CTC with strong HER2 staining. The presence of HER2-positive CTCs was not associated with tumor size (p = 0.335), histopathological grading (p = 0.976), hormone receptor status (ER: p = 0.626, PR: p = 0.263) or axillary lymph node involvement (p = 0.430). Overall, 83 (32.2%) of the CTC-positive patients exclusively had CTCs with strong HER2 staining, whereas 31 (12.0%) had only CTCs with negative HER2 staining. Within-sample variation in the HER2 status of CTCs was found in 86 (57.8%) of the 149 patients with more than 1 CTC., Conclusion: This study demonstrated that discordance between the HER2 expression of CTCs and that of the primary tumor frequently occurs in early breast cancer. Future follow-up evaluation will assess whether this discrepancy may contribute to trastuzumab resistance.

Purpose: The aim of the ongoing DETECT study program is to evaluate therapeutic intervention based on phenotypes of circulating tumor cells (CTC) in patients with metastatic breast cancer (MBC). Currently (as of July 2015) more than half of the projected about 2000 patients with MBC have already been screened for CTC., Methods: Women with HER2-negative primary tumor and presence of CTC are recruited into different DETECT trials according to the HER2-phenotype of CTC. Patients with HER2-positive CTC are randomized to treatment with physicians' choice therapy (standard chemo- or endocrine therapy) with or without additional HER2-targeted therapy with lapatinib in the DETECT III trial. In DETECT IVa, postmenopausal patients with hormone-receptor positive primary cancer and HER2-negative CTC receive everolimus and standard endocrine therapy. For women with HER2-negative CTC and triple negative MBC or hormone-receptor positive tumor and indication for chemotherapy, a treatment with eribulin is offered (DETECT IVb). The clinical efficacy is investigated by CTC-Clearance and progression-free survival (PFS). The DETECT V/CHEVENDO trial extends the DETECT study program for women with HER2-positive and hormone-receptor positive MBC. The primary objective of this trial is to compare safety and quality of life (QoL) as assessed by the occurrence of adverse events in patients treated with dual (trastuzumab plus pertuzumab) HER2-targeted therapy plus either endocrine or chemotherapy. The translational research projects of the DETECT study program focus on further molecular characterization of CTC and evaluation of markers for their suitability to predict treatment response and to facilitate the development of more personalized treatment options.

Purpose: Today's surgical standard of care for uterine leiomyomas is laparoscopic and/or vaginal surgery with larger specimens requiring morcellation to avoid open surgery. This is often associated with intra-abdominal dissemination of cellular material which in case of a uterine sarcoma might result in iatrogenic seeding of malignant tumor cells. The aim of this systematic literature review is to evaluate the surgical techniques and the impact of accidental tumor morcellation on the outcome of patients postoperatively diagnosed with malignant uterine sarcomas., Methods: The National Library of Medicine database (pubmed) and Web of science were searched individually using three different search terms ('morcel* sarcoma', 'survival, sarcoma, treatment, Uter*', and 'disease free survival, sarcoma, treatment, uter*'). After excluding duplicates and screening for relevance, 16 articles were left for full-text review, resulting in seven case series with more than 5 patients., Results: The case numbers range from 14 to 123 patients with the majority of cases being leiomyosarcomas., Conclusion: There is no reliable diagnostic tool to differentiate a fibroid from a uterine sarcoma preoperatively. Tumor morcellation occurs in various open and closed surgical techniques and is not limited to laparoscopic surgery only. There is an urgent need for a presurgical diagnostic parameter.

Background: The diagnosis of extrauterine pregnancy is possible very early giving the patient and doctors treatment options. As the risks and success rate of medical and surgical treatment are similar, the decision is increasingly influenced by cost-effectiveness., Objective: The following article systematically reviews the known literature regarding cost, decision criteria and possible follow-up., Methods: Literature review of extrauterine gravity in combination with cost in the online National Library of Medicine since 1.1.1997 following the PRISMA recommendations., Results: Six articles were identified in which the cost of the laparoscopic versus medical treatment is reviewed. In five articles, the medical treatment was shown to be more cost effective and in the sixth article the costs were found to be equal. The cost saving varies between 18 and 88% depending on the consideration of direct and indirect costs. If indirect expenses are considered, the total sum increases with treatment failures. Failure rates are given as up to 27% depending on the type of failure (surgical or medical). These rates seem to be linked indirectly with the β-HCG levels. Predictive parameters for the successful medical treatment are missing., Conclusions: The treatment of small extrauterine gravidities in haemodynamically stable patients (defined by HCG levels <1,500 IU/l) is medically successful and cost-effective. With HCG levels between 1,500 IU/l and 3,000 IU/l, the treatment costs are similar. HCG levels >5,000 IU/l favour the surgical treatment as being more cost-effective. A similar cut-off for the sonographic imaging is missing.

Background: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare., Material and Methods: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC., Results: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001)., Conclusion: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.