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Objectives Many women with early-stage, hormone receptor-positive breast cancer may not benefit from adjuvant chemotherapy. Gene expression tests can reduce chemotherapy over- and undertreatment by providing prognostic information on the likelihood of recurrence and, with Onco type DX, predictive information on chemotherapy benefit. These tests are currently not reimbursed by German healthcare payers. An analysis was conducted to evaluate the budget impact of gene expression tests in Germany. Materials and methods Costs of gene expression tests and medical and non-medical costs associated with treatment were assessed from healthcare payer and societal perspectives. Costs were estimated from data collected at a university hospital and were combined with decision impact data for Onco type DX, MammaPrint, Prosigna and EndoPredict (EPclin). Changes in chemotherapy use and budget impact were evaluated over 1 year for 20,000 women. Results Chemotherapy was associated with substantial annual costs of EUR 19,003 and EUR 84,412 per therapy from the healthcare payer and societal perspective, respectively. Compared with standard care, only Onco type DX was associated with cost savings to healthcare payers and society (EUR 5.9 million and EUR 253 million, respectively). Scenario analysis showed that both women at high clinical but low genomic risk and low clinical but high genomic risk were important contributors to costs. Conclusions Onco type DX was the only gene expression test that was estimated to reduce costs versus standard care in Germany. The reimbursement of Onco type DX testing in standard clinical practice in Germany should be considered. [ABSTRACT FROM AUTHOR]

Purpose: Despite patients' widespread use and acceptance of complementary and integrative medicine (IM), few data are available regarding health-care professionals' current implementation of it in clinical routine. A national survey was conducted to assess gynecologists' attitudes to and implementation of complementary and integrative treatment approaches., Methods: The Working Group on Integrative Medicine of the German Society of Gynecological Oncology conducted an online survey in collaboration with the German Society of Gynecology and Obstetrics (DGGG) in July 2019. A 29-item survey was sent to all DGGG members by email., Results: Questionnaires from 180 gynecologists were analyzed, of whom 61 were working office-based in private practice and 95 were employed in hospitals. Seventy percent stated that IM concepts are implemented in their routine clinical work. Most physicians reported using IM methods in gynecological oncology. The main indications for IM therapies were fatigue (n = 98), nausea and vomiting (n = 89), climacteric symptoms (n = 87), and sleep disturbances (n = 86). The most commonly recommended methods were exercise therapy (n = 86), mistletoe therapy (n = 78), and phytotherapy (n = 74). Gynecologists offering IM were more often female (P = 0.001), more often had qualifications in anthroposophic medicine (P = 0.005) or naturopathy (P = 0.019), and were more often based in large cities (P = 0.016)., Conclusions: There is strong interest in IM among gynecologists. The availability of evidence-based training in IM is increasing. Integrative therapy approaches are being implemented in clinical routine more and more, and integrative counseling services are present all over Germany. Efforts should focus on extending evidence-based knowledge of IM in both gynecology and gynecological oncology.

Background/aim: Subcutaneous Herceptin (HER SC) has been shown to be equally effective and safe compared to intravenous Herceptin (HER i.v.) application in early HER2-positive breast cancer (HER2+ BC). However, real-world data from the subcutaneous application are currently limited., Patients and Methods: Based on a non-interventional study (NIS), data from routine clinical use of HER SC have been gathered between 2013 and 2018 in 135 hospitals and open-care practices throughout Germany., Results: A total of 265 patients were recruited in the neo-adjuvant and 605 patients in the adjuvant setting. Primary effectiveness endpoint in the neoadjuvant treatment setting was pathological complete response rate, which was achieved in 41.5%. Primary endpoint in the adjuvant setting was disease free survival rate after 2 years (94.9%). Safety results from the study were comparable to the well-known safety profile of HER i.v. including preferred terms, incidence, severity, including cardiac events. No new safety signals were detected., Conclusion: Effectiveness and safety of HER SC were comparable to data from HER i.v. in early HER2+ BC., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hexachlorocyclohexanes (HCHs) are widespread and persistent environmental pollutants, which cause heavy contamination in soil, sediment and groundwater. An anaerobic consortium, which was enriched on β-HCH using a soil sample from a contaminated area of a former pesticide factory, was capable to transform α, β, γ, and δ-HCH via tetrachlorocyclohexene isomers stoichiometrically to benzene and chlorobenzene. The carbon and chlorine isotope enrichment factors (ε C and ε Cl ) of the dehalogenation of the four isomers ranged from -1.9 ± 0.3 to -6.4 ± 0.7‰ and from -1.6 ± 0.2 to -3.2 ± 0.6‰, respectively, and the correlation of δ 37 Cl and δ 13 C (Λ values) of the four isomers ranged from 1.1 ± 0.1 to 2.4 ± 0.2. The evaluation of Λ and the apparent kinetic isotope effects (AKIE) for carbon and chlorine may lead to the hypothesis that the two eliminated chlorine atoms of α- and γ-HCH were in axial positions, the same as for the β-HCH conformer which has six chlorine atoms in axial positions after ring flip. The dichloroelimination of δ-HCH resulted in distinct AKIE and Λ values as one chlorine atom is in axial whereas the other chlorine atoms are in the equatorial positions. Significant chlorine and carbon isotope fractionations of HCH isomers were observed in the samples from a contaminated aquifer (Bitterfeld, Germany). The 37 Cl/ 35 Cl and 13 C/ 12 C isotope fractionation patterns of HCH isomers from laboratory experiments were used diagnostically in a model to characterize microbial dichloroelimination in the field study. The comparison of isotope fractionation patterns indicates that the transformation of HCH isomers at the field was mainly governed by microbial dichloroelimination transformation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The impact of locoregional radiotherapy (RT) after neoadjuvant chemotherapy (NACT) and mastectomy in breast cancer patients is currently unclear. Several publications have suggested that patients with a favorable response to NACT might not benefit from RT after mastectomy., Methods: A retrospective analysis of three prospective randomized NACT trials was performed. Information on the use of RT was available for 817 breast cancer patients with non-inflammatory breast cancer who underwent mastectomy after NACT within the GeparTrio, GeparQuattro, and GeparQuinto-trials. RT was administered to 676 of these patients (82.7%)., Results: The 5-year cumulative incidence of locoregional recurrence (LRR) was 15.2% (95% confidence interval [CI] 9.0-22.8%) in patients treated without RT and 11.3% in patients treated with RT (95% CI 8.7-14.3%). In the multivariate analysis, RT was associated with a lower risk of LRR (hazard ratio 0.51, 95% CI 0.27-1.0; p = 0.05). This effect was shown especially in patients with cT3/4 tumors, as well as in patients who were cN+ before neoadjuvant therapy, including those who converted to ypN0 after neoadjuvant therapy. In the bivariate analysis, disease-free survival was significantly worse in patients who received RT, however this was not confirmed in the multivariate analysis., Conclusions: Our results suggest that RT reduces the LRR rates in breast cancer patients who receive a mastectomy after NACT without an improvement in DFS. Prospective randomized controlled trials such as the National Surgical Adjuvant Breast and Bowel Project B-51/RTOG 1304 trial will analyze whether RT has any benefit in patients who have a favorable response after NACT.

Background: Distortion of taste sensations is a common chemotherapy-induced side effect; however, treatment evidence is limited. Pilot data indicated that acupuncture might be able to improve symptoms of dysgeusia. Thus, the aim of this study is to investigate the effects and side effects of hypoglossal acupuncture in the treatment of dysgeusia in patients with breast cancer undergoing chemotherapy., Methods/design: The study is a randomized controlled trial comparing a single verum acupuncture treatment with two active comparators: sham acupuncture and dietary recommendations. Sample size calculation revealed a total of 75 patients pending an alpha of 0.05, a power of 0.8, and an estimated effect size of 0.80. Patients with breast cancer undergoing platinum- or taxane-based chemotherapy will be included if they present with phantogeusia (abnormal taste sensations without an external oral stimulus) with an intensity of 4 points or above on an 11-point numeric rating scale (NRS). The primary outcome is phantogeusia; secondary outcomes include parageusia (abnormal taste of food), hypogeusia (reduced taste sensations), hypergeusia (increased taste sensations), xerostomia (dry mouth), stomatitis, appetite, and functional impairment. All outcomes will be assessed at baseline and prior to the next chemotherapy administration using an 11-point NRS for each. All adverse events will be recorded., Discussion: The results of this study will demonstrate the extent to which hypoglossal acupuncture may influence the intensity of and functional impairment due to chemotherapy-induced dysgeusia., Trial Registration: Clinical Trials.gov, NCT02304913 . Registered on 19 November 2014.

Background: Hospitalisations are a critical event in the care process. Insufficient communication and uncoordinated follow-up care often impede the recovery process of the patient resulting in a high number of rehospitalisations and increased health care costs. The overall aim of this study is the development, implementation and evaluation of a structured programme (VESPEERA) to improve the admission and discharge process., Methods: We will conduct an open quasi-experimental multi-centre study with four intervention arms. A cohort selected from insurance claims data will serve as a control group reflecting usual care. The intervention will be implemented in 25 hospital departments and 115 general practices in 9 districts in Baden-Wurttemberg. Eligibility criteria for patients are: age > 18 years, hospital admission or hospitalisation, insurance at the sickness fund "AOK Baden-Wurttemberg", enrolment in general practice-centred care contract. Each study arm will receive different intervention components based on the point of study enrolment and the patient's medical need. The interventions comprise a) a structured assessment in the general practice prior to admission resulting in an admission letter b) a discharge conversation by phone between hospital and general practice, c) a structured assessment and care plan post-discharge and d) telephone monitoring for patients with a high risk of rehospitalisation. The assessments are supported by a software tool ("CareCockpit"), originally developed for structured case management programmes. The primary outcome (rehospitalisation due to the same indication within 90 days) and a range of secondary outcomes (rehospitalisation due to the same indication within 30 days; hospitalisations due to ambulatory care-sensitive conditions; delayed prescription of medication and medical products/ devices and referral to other health practitioner/s after discharge; utilisation of emergency or rescue services within 3 months; average care cost per year and patient participating in the VESPEERA programme) and quality indicators will be determined based on insurance claims data and CareCockpit data. Additionally, a patient survey on satisfaction with cross-sectoral care and health related quality of life will be conducted., Discussion: Based on the results, area-wide implementation in usual care is well sought. This study will contribute to an improvement of cross-sectoral care during the admission and discharge process., Trial Registration: DRKS00014294 on DRKS / Universal Trial Number (UTN): U1111-1210-9657, Date of registration 12/06/2018.

Background: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC)., Patients and Methods: Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m 2 ) followed by P (225 mg/m 2 ) followed by C (2000 mg/m 2 ), each q2w for 3 cycles or weekly P (80 mg/m 2 ) plus M (20 mg/m 2 ) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344., Results: 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77-1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died., Conclusions: In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment., Patients and Methods: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses., Results: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84)., Conclusions: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration., Clinical Trials Number: CFEM345DDE19., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany., Methods: A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually., Results: The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care., Limitations: Country-specific data on the risk of distant recurrence and quality-of-life were not available., Conclusions: Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current standard of care women with ER+, HER2- early-stage breast cancer.

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.