Publications by authors named "Wolfgang Janni"

310 Publications

Novel and flexible ultrasound simulation with smartphones and tablets in fetal echocardiography.

Arch Gynecol Obstet 2021 Jun 4. Epub 2021 Jun 4.

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

Purpose: Evaluation of a novel ultrasound-simulation-app for training fetal echocardiography as a possible useful addition for students, residents and specialist doctors. Furthermore, comparison to a conventional learning-method with special attention on orientation and recognition of physiological structures.

Methods: Prospective two-arm study with the participation of 226 clinical students. 108 students were given an extract from a textbook on fetal echocardiography (PDF-group, n = 108) for 30 min to study. 118 students were able to use the new ultrasound-simulator-app (Simulator-group, n = 118) to learn for 30 min. The knowledge of the students was examined both before and after the learning-period by having them identify sonographic structures in videos using single-choice selection.

Results: There were no significant differences between the two groups regarding age (p = 0.87), gender (p = 0.28), and the number of previously performed ultrasound-examinations (p = 0.45). In the Simulator-group, there was a significantly higher learning effect regarding the proportion of students with an increase of correct answers in the video test examination (p = 0.005). At the end of learning, the students in the Simulator-group needed significantly less time to display the structures in the app's simulation (median initially 10.9 s vs. 6.8 s at the end; p < 0.001).

Conclusions: The novel ultrasound-simulation-app seems to be a useful addition and improvement to ultrasound training. Previous difficulties such as simultaneously having patients, ultrasound-machines, and professors at disposal can thus be avoided. This means that another important step towards remote learning can be taken, which has been proven increasingly essential lately, due to the COVID-19 pandemic.
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http://dx.doi.org/10.1007/s00404-021-06102-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175929PMC
June 2021

Update Breast Cancer 2021 Part 2 - Advanced Stages, Long-Term Consequences and Biomarkers.

Geburtshilfe Frauenheilkd 2021 May 3;81(5):539-548. Epub 2021 May 3.

Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Leipzig, Leipzig, Germany.

This review summarises and discusses significant aspects of recently published studies on patient treatment in advanced breast cancer and on biomarkers in breast cancer. In recent years, a large number of drugs for all molecular subtypes have been developed up to phase III trials. With regard to immune checkpoint inhibitors in metastasised breast cancer, the recent discussion has centred on the best candidate for combined chemotherapy. The oral taxanes could become a new type of oral chemotherapies. There is a growing body of data on biomarkers for the use of CDK4/6 inhibitors, which could also signify further development for other molecular subtypes. New substances have been developed for metastatic HER2+ breast cancer that still result in good remission even after massive prior treatment and/or cerebral metastasis. Similarly, knowledge is growing about targeted therapies with antibody-drug conjugates (ADC) against Trop-2, which could bolster our therapeutic armoury in triple-negative breast cancer (TNBC). In addition, the clinical focus is on understanding how to maintain fertility after breast cancer treatment. Here, pooled analyses provide new insights.
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http://dx.doi.org/10.1055/a-1464-1221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137275PMC
May 2021

Update Breast Cancer 2021 Part 1 - Prevention and Early Stages.

Geburtshilfe Frauenheilkd 2021 May 3;81(5):526-538. Epub 2021 May 3.

Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt, Germany.

This review summarises not only the latest evidence on prevention, but also the current research on the treatment of early-stage breast cancer patients. Recent years have seen a growing body of evidence on the risk of high- and moderate-penetrance breast cancer susceptibility genes. A large international consortium has now been able to further refine the answer to the question of the significance of the so-called panel genes. Moreover, the data on treatment selection regarding endocrine efficacy and the decision for or against chemotherapy have also been advanced markedly. There is also new data on adjuvant CDK4/6 (cyclin-dependent kinase 4/6) inhibitors, which are standard in first-line treatment in patients with metastatic HER2-negative, hormone receptor-positive (HR+) breast cancer. For other therapies such as immune checkpoint inhibitors, which have successfully improved the rate of pathologic complete response (pCR) in neoadjuvant treatment settings for patients with triple-negative breast cancer (TNBC), there is a growing understanding of the quality of life and side effects. This is especially important in situations where patients could possibly be cured without such a regimen.
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http://dx.doi.org/10.1055/a-1464-0953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137274PMC
May 2021

Challenges and Opportunities for Real-World Evidence in Metastatic Luminal Breast Cancer.

Breast Care (Basel) 2021 Apr 16;16(2):108-114. Epub 2021 Mar 16.

Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany.

Background: The therapeutic armamentarium for patients with metastatic breast cancer is becoming more and more specific. Recommendations from clinical trials are not available for all treatment situations and patient subgroups, and it is therefore important to collect real-world data.

Summary: To develop recommendations for up-to-date treatments and participation in clinical trials for patients with metastatic breast cancer, the Prospective Academic Translational Research PRAEGNANT Network was established to optimize the quality of oncological care in the advanced therapeutic setting. The main aim of PRAEGNANT is to systematically record medical care for patients with metastatic breast cancer in the real-life setting, including the outcome and side effects of different treatment strategies, to monitor quality-of-life changes during therapy, to identify patients eligible for participation in clinical studies, and to allow targeted therapies based on the molecular structures of breast carcinomas.

Key Messages: This article describes the PRAEGNANT network and sheds light on the question of whether the various end points from clinical trials can be transferred to the real-world treatment situation.
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http://dx.doi.org/10.1159/000515701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114055PMC
April 2021

A Scary Complication: Single-center Study on Management and Outcome of Cesarean Scar Pregnancy.

Rev Bras Ginecol Obstet 2021 Apr 12;43(4):311-316. Epub 2021 May 12.

Department of Obstetrics and Gynecology, Ulm University, Ulm, Germany.

A cesarean scar pregnancy (CSP) is a scary and life-threatening complication of cesarean section (CS). Nevertheless, the incidence of CS is constantly growing. The CSP incidence is 0,15% of pregnancies after CS which represents 6,1% of all ectopic pregnancies in women with condition after CS. Therefore, it should be more present in the clinical daily routine. From mild nonspecific symptoms to hypovolemic shock, diagnosis and therapy must be performed quickly. With the progressive growth of the scar pregnancy, a uterine rupture involves the risk of severe bleeding, and an emergency hysterectomy could be necessary. Prolongation of pregnancy has been successful only in a few cases. We report 11 cases from our hospital in the past 10 years. In the discussion, treatment options of this complication with an increasing incidence, which is associated with serious morbidity and mortality, are presented based on the current literature. Treatment options include drug therapy, but also surgical or combined procedures with radiological intervention.
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http://dx.doi.org/10.1055/s-0041-1728781DOI Listing
April 2021

[Focus on breast cancer].

Gynakologe 2021 6;54(5):307-308. Epub 2021 May 6.

Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Prittwitzstr. 43, 89075 Ulm, Deutschland.

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http://dx.doi.org/10.1007/s00129-021-04797-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101343PMC
May 2021

Two-year follow-up after a six-week high-intensity training intervention study with breast cancer patients: physiological, psychological and immunological differences.

Disabil Rehabil 2021 May 11:1-8. Epub 2021 May 11.

Division of Sports and Rehabilitation Medicine, Ulm University Hospital, Ulm, Germany.

Purpose: Previously we demonstrated the feasibility of a six-week-long combination of high-intensity interval endurance and strength training (HIT/HIRT) for women with nonmetastatic breast cancer leading to improvements in psychological well-being and performance. Now we report results of a 24-month follow-up.

Methods: Previous intervention (IG,  = 10; 58.7 ± 8.4yrs) and control group (CG,  = 9; 58.8 ± 6.6yrs) were asked for follow-up examinations 12 (T12) and 24 months (T24) after cessation of the supervised training (POST). Medical history, mental well-being, performance and immunological variables were analyzed with respect to intervention start (PRE).

Results: IG maximum oxygen consumption (⩒O) 12%-improved POST ( = 0.05) and declined to baseline values T24, while CG ⩒O increased 12% T24 ( = 0.01). IG strength (1RM) increased 31% POST ( < 0.001) and remained above baseline level T24 ( = 0.003), whereas CG 1RM slightly improved T24 (+19%,  = 0.034). IG Anxiety and Depression decreased POST and did not change until T24. IG C-reactive protein decreased POST and increased to pre-exercise levels T24. CG immunological/inflammatory/life quality markers did not change.

Conclusions: Six weeks of HIT/HIRT by breast cancer patients can induce similar beneficial effects like two years of convalescence, but outcomes were unstable and showed a fast backslide in aerobic capacity, activity level and in pro-inflammatory state within 12 months.IMPLICATIONS FOR REHABILITATIONHigh-intensity interval endurance and strength training (HIT/HIRT) for female breast cancer patients was shown to improve psychological well-being and performance, but long-term effects/adherence are unknown.Significant backslides in aerobic capacity, activity level as well as in the pro-inflammatory response after one and two years are observed and should be monitored.Continuous supervision and/or support of breast cancer patients before, during, and after medical care due to poor training adherence when voluntarily executed is recommended.
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http://dx.doi.org/10.1080/09638288.2021.1921861DOI Listing
May 2021

Age-related activity of Poly (ADP-Ribose) Polymerase (PARP) in men with localized prostate cancer.

Mech Ageing Dev 2021 Jun 19;196:111494. Epub 2021 Apr 19.

Department of Obstetrics and Gynecology, Ulm University, Prittwitzstrasse 43, 89075, Ulm, Germany. Electronic address:

Mutations in DNA repair genes have been connected with familial prostate cancer and sensitivity to targeted drugs like PARP-inhibitors. Clinical use of this information is limited by the small fraction of prostate cancer risk gene carriers, variants of unknown pathogenicity and the focus on monogenic disease mechanisms. Functional assays capturing mono- and polygenic defects were shown to detect breast and ovarian cancer risk in blood-derived cells. Here, we comparatively analyzed lymphocytes from prostate cancer patients and controls applying a sensitive DNA double-strand break (DSB) repair assay and a flow cytometrybased assay measuring the activity of Poly(ADP-Ribose)-Polymerase, a target in treatment of metastatic prostate cancer. Contrary to breast and ovarian cancer patients, error-prone DNA double-strand break repair was not activated in prostate cancer patients. Yet, the activity of PARP discriminated between prostate cancer cases and controls. PARylation also correlated with the age of male probands, suggesting male-specific links between mutation-based and aging-associated DNA damage accumulation and PARP. Our work identifies prostate cancer-specific DNA repair phenotypes characterized by increased PARP activities and carboplatin-sensitivities, detected by functional testing of lymphocytes. This provides new insights for further investigation of PARP and carboplatin sensitivity as biomarkers in peripheral cells of men and prostate cancer patients.
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http://dx.doi.org/10.1016/j.mad.2021.111494DOI Listing
June 2021

Update Breast Cancer 2020 Part 5 - Moving Therapies From Advanced to Early Breast Cancer Patients.

Geburtshilfe Frauenheilkd 2021 Apr 14;81(4):469-480. Epub 2021 Apr 14.

Frauenklinik, Universitätsklinikum Augsburg, Augsburg, Germany.

In recent years, significant progress has been made in new therapeutic approaches to breast cancer, particularly in patients with HER2-positive and HER2-negative/hormone receptor-positive (HR+) breast cancer. In the case of HER2-positive tumours, these approaches have included, in particular, treatment with pertuzumab, T-DM1, neratinib and, soon, also tucatinib and trastuzumab deruxtecan (neither of which has yet been authorised in Europe). In patients with HER2-/HR+ breast cancer, CDK4/6 inhibitors and the PIK3CA inhibitor alpelisib are of particular importance. Further novel therapies, such as Akt kinase inhibitors and oral SERDs (selective estrogen receptor down regulators), are already being investigated in ongoing clinical trials. These therapeutic agents are not only being introduced into curative, (neo-)adjuvant therapeutic settings for HER2-positive tumours; a first favourable study on abemaciclib as an adjuvant therapy has now also been published. In patients with triple-negative breast cancer, after many years of negative study results with the Trop-2 antibody drug conjugate (ADC) sacituzumab govitecan, a randomised study has been published that may represent a significant therapeutic advance. This review describes the latest developments in breast cancer subsequent to the ESMO Congress 2020.
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http://dx.doi.org/10.1055/a-1397-7170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046519PMC
April 2021

Mutations in and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis.

J Clin Oncol 2021 May 29;39(15):1619-1630. Epub 2021 Mar 29.

Department of Gynecology and Obstetrics, Carl Gustav Carus Faculty of Medicine and University Hospital, Technical University of Dresden, Dresden, Germany.

Purpose: Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome.

Patients And Methods: Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed.

Results: Germline mutations in 12 established BC predisposition genes (including and ) were detected in 271 (10.4%) patients. A mutation in or was seen in 129 patients (5.0%). mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% 6.6%, < .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC.

Conclusion: Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.
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http://dx.doi.org/10.1200/JCO.20.01200DOI Listing
May 2021

Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial.

JAMA Oncol 2021 Apr;7(4):565-572

German Breast Group, GBG Forschungs GmbH Neu-Isenburg, Germany.

Importance: The extent of changes in estradiol levels in male patients with hormone receptor-positive breast cancer receiving standard endocrine therapies is unknown. The sexual function and quality of life related to those changes have not been adequately evaluated.

Objective: To assess the changes in estradiol levels in male patients with breast cancer after 3 months of therapy.

Design, Setting, And Participants: This multicenter, phase 2 randomized clinical trial assessed 56 male patients with hormone receptor-positive breast cancer. Patients were recruited from 24 breast units across Germany between October 2012 and May 2017. The last patient completed 6 months of treatment in December 2017. The analysis data set was locked on August 24, 2018, and analysis was completed on December 19, 2018.

Interventions: Patients were randomized to 1 of 3 arms: tamoxifen alone or tamoxifen plus gonadotropin-releasing hormone analogue (GnRHa) or aromatase inhibitor (AI) plus GnRHa for 6 months.

Main Outcomes And Measures: The primary end point was the change in estradiol levels from baseline to 3 months. Secondary end points were changes of estradiol levels after 6 months, changes of additional hormonal parameters, adverse effects, sexual function, and quality of life after 3 and 6 months.

Results: In this phase 2 randomized clinical trial, a total of 52 of 56 male patients with a median (range) age of 61.5 (37-83) years started treatment. A total of 3 patients discontinued study treatment prematurely, 1 in each arm. A total of 50 patients were evaluable for the primary end point. After 3 months the patients' median estradiol levels increased by 67% (a change of +17.0 ng/L) with tamoxifen, decreased by 85% (-23.0 ng/L) with tamoxifen plus GnRHa, and decreased by 72% (-18.5 ng/L) with AI plus GnRHa (P < .001). After 6 months, median estradiol levels increased by 41% (a change of +12 ng/L) with tamoxifen, decreased by 61% (-19.5 ng/L) with tamoxifen plus GnRHa, and decreased by 64% (-17.0 ng/L) with AI plus GnRHa (P < .001). Sexual function and quality of life decreased when GnRHa was added but were unchanged with tamoxifen alone.

Conclusions And Relevance: This phase 2 randomized clinical trial found that AI or tamoxifen plus GnRHa vs tamoxifen alone led to a sustained decrease of estradiol levels. The decreased hormonal parameters were associated with impaired sexual function and quality of life.

Trial Registration: ClinicalTrials.gov Identifier: NCT01638247.
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http://dx.doi.org/10.1001/jamaoncol.2020.7442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863014PMC
April 2021

Rationale and description of a lifestyle intervention programme to achieve moderate weight loss in women with non-metastatic breast cancer: the lifestyle intervention part of the SUCCESS C Study.

BMJ Nutr Prev Health 2020 Dec 21;3(2):213-219. Epub 2020 Sep 21.

Else Kroener-Fresenius-Centre for Nutritional Medicine, Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.

Objective: There is growing evidence from observational studies that lifestyle factors such as obesity, an unhealthy diet and lack of physical activity are associated with poor long-term outcome in women with breast cancer. The primary objective of the lifestyle modification part of the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS C) Trial is to investigate the effect of an individualised lifestyle intervention programme aiming at moderate weight loss on disease-free survival in women with HER2/neu-negative breast cancer. Secondary objectives include the effect of the intervention on body weight, cardiovascular risk and quality of life.

Methods: The SUCCESS C Trial is an open-label, multicentre, randomised controlled phase III study using a 2×2 factorial design in women with newly diagnosed HER2/neu-negative intermediate-risk to high-risk breast cancer. The first randomisation served to compare disease-free survival in patients treated with two different chemotherapy regimens (3642 participants). The second randomisation served to compare disease-free survival in patients with a body mass index of 24-40 kg/m² (2292 participants) receiving either a telephone-based individualised lifestyle intervention programme for moderate weight loss or general recommendations for a healthy lifestyle for 2 years. Outcome analyses will be conducted after 5 years of follow-up.

Perspective: This study will provide information on the efficacy and safety of a comprehensive lifestyle intervention programme on disease-free survival in a large cohort of women with breast cancer. EU Clinical Trials Identifier: 2008-005453-38.
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http://dx.doi.org/10.1136/bmjnph-2020-000119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841841PMC
December 2020

Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium.

Cancer Epidemiol Biomarkers Prev 2021 Apr 26;30(4):623-642. Epub 2021 Jan 26.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype ( > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026532PMC
April 2021

Therapy Algorithms for the Diagnosis and Treatment of Patients with Early and Advanced Breast Cancer.

Breast Care (Basel) 2020 Dec 2;15(6):608-618. Epub 2020 Nov 2.

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Background: In order to offer optimal treatment approaches based on available evidence, the Commission Breast of the Working Group Gynecologic Oncology (AGO) of the German Cancer Society developed therapy algorithms for eight complex treatment situations in primary and advanced breast cancer.

Summary: Therapy algorithms for the following complex treatment situations are outlined in this paper: (neo)adjuvant therapy of human epidermal growth factor receptor 2 (HER2)-positive breast cancer; axillary surgery and neoadjuvant chemotherapy; adjuvant endocrine therapy in premenopausal patients; adjuvant endocrine therapy in postmenopausal patients; hormone receptor (HR)-positive/HER2-negative metastatic breast cancer: strategies; HR-positive/HER2-negative metastatic breast cancer: endocrine-based first-line treatment; HER2-positive metastatic breast cancer: first to third-line; metastatic triple-negative breast cancer.

Key Messages: The therapy options shown in these algorithms are based on the current AGO recommendations updated in January 2020 but cannot represent all evidence-based treatment options. Prior therapies, performance status, comorbidities, patient preference, etc. must be taken into account for the actual treatment choice. Therefore, in individual cases, other evidence-based treatment options not listed here may also be appropriate and justified.
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http://dx.doi.org/10.1159/000511925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768141PMC
December 2020

Choosing a Surgical Access Point for Hysterectomy: A Paradigm Shift Over a 10-Year Span.

Front Med (Lausanne) 2020 25;7:569895. Epub 2020 Nov 25.

Medical Psychology Division, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Hospital, Ulm, Germany.

When choosing a surgical procedure for a hysterectomy, doctors and patients have various options in terms of the multiple surgical access points available. The aim of this study was to descriptively analyze developments concerning the surgical access point selected over the past 10 years at Ulm University Hospital, (south) Germany, assess the variables associated with the surgical method and explore any potential significant correlations that influence these surgical access routes. Explicitly, we wished to investigate whether the approval of ulipristal acetate and the warning issued by the Food and Drug Administration (FDA) in connection with its use changed existing trends. This monocentric study retrospectively assessed data from all patients who underwent a hysterectomy due to a benign disease or endometrial cancer from January 2007 until December 2016. Of the benign indications considered, myomas and descensus genitalis occurred most frequently (49.5 and 30.6%, respectively). The percentage of abdominal procedures declined from 61.4 to 13.4% between 2007 and 2016 for all hysterectomies, whilst it increased from 4.1 to 69.7% for laparoscopic hysterectomies. The rate of vaginal hysterectomies increased to 45.5% until 2013 and declined in the years afterwards. Laparoscopic assisted vaginal hysterectomies were comparatively rare. The trends in terms of surgical routes were similar for endometrial cancer. During the observation period, the share of abdominal hysterectomies fell from 100 to 11.3%, whilst the share of laparoscopic hysterectomies increased from 0 to 86.6%. The other two procedures were less frequently used. Use of the laparoscopic hysterectomy procedure also increased significantly after the FDA's 2014 warning. Ulipristal acetate may have tended to influence the process. Contrary to the national decrease in hysterectomy numbers, the annual number of hysterectomies at Ulm University Hospital remained stable during the observation period. Nevertheless, there was a clear shift in the preferred surgical routes for hysterectomy.
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http://dx.doi.org/10.3389/fmed.2020.569895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724105PMC
November 2020

Fishing for (in)continence: long-term follow-up of women with OASIS-still a taboo.

Arch Gynecol Obstet 2021 04 1;303(4):987-997. Epub 2020 Dec 1.

Department of Gynaecology and Obstetrics, Ulm University Hospital, Ulm, Germany.

Purpose: Obstetric anal sphincter injuries (OASIS) increase the risk for pelvic floor dysfunctions. The goal of this study was to examine the long-term outcomes after OASIS on pelvic floor functions and quality of life.

Material And Methods: Between 2005 and 2013, 424 women had an OASIS at the Women University Hospital Ulm. Out of these 71 women completed the German pelvic floor questionnaire, which includes questions regarding prolapse symptoms as well as bladder, bowel and sexual function. In addition, 64 women were physically examined, including a speculum examination to evaluate the degree of prolapse, a cough test to evaluate urinary stress incontinence (SI) and an evaluation of both pelvic floor sphincter (modified Oxford score) and anal sphincter contraction.

Results: A high rate of pelvic floor disorders after OASIS was found, as 74.6% of women reported SI, 64.8% flatus incontinence and 18.3% stool incontinence, respectively. However, only few women stated a substantial negative impact on quality of life. The clinical examination showed that a positive cough test, a weak anal sphincter tone and a diagnosed prolapse correlated with the results of the self-reported questionnaire.

Conclusion: On one hand, OASIS has an influence on pelvic floor function going along with lots of complaints, while on the other hand, it still seems to be a taboo topic, as none of the participants spoke about the complaints after OASIS with a doctor. Therefore, the gynecologist should actively address these issues and offer therapy options for the women with persisting problems.
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http://dx.doi.org/10.1007/s00404-020-05878-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985110PMC
April 2021

[Incarceration of the Gravid Uterus in the Second Trimester - Diagnostics, Successful Therapy and Review of Literature].

Z Geburtshilfe Neonatol 2021 Apr 12;225(2):176-179. Epub 2020 Nov 12.

Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Ulm, Ulm.

A rare complication in obstetrics is the incarceration of the gravid uterus. If the uterus remains retroverted, the fundus persists in the pelvic cavity. Due to growth, the familiar anatomy of the uterus changes and undetected incarceration can lead to a serious maternal morbidity. Early treatment can enable a normal prolongation of pregnancy. In our case, we report a first gravida with initial diagnosis of a posterior sacculation of the uterus in the 21st week of pregnancy. After confirmed diagnosis by MRI, the reduction of the uterus by vaginal digital lifting of the uterus and simultaneous rectoscopic CO2 filling was successful. A spontaneous delivery without complications after rupture of membranes followed in the 35th week of pregnancy.
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http://dx.doi.org/10.1055/a-1285-8338DOI Listing
April 2021

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

BMC Cancer 2020 Nov 11;20(1):1091. Epub 2020 Nov 11.

Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.

Methods: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.

Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.

Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.

Trial Registration: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.
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http://dx.doi.org/10.1186/s12885-020-07546-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656772PMC
November 2020

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine.

Geburtshilfe Frauenheilkd 2020 Nov 6;80(11):1134-1142. Epub 2020 Nov 6.

Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany.

Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment. The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with a focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the patient characteristics and descriptive prognostic data for HER2-positive patients who have completed a treatment with T-DM1. Therapy patterns after T-DM1 and progression-free survival are reported as well as overall survival. A total of 85 patients were identified for the study who were prospectively observed during therapy after the termination of T-DM1. The main reason for T-DM1 termination was progress. Following T-DM1, lapatinib, trastuzumab and chemotherapy were the main therapy choices. Median progression-free survival was 4.8 months (95% CI: 3.2 - 6.3) and median overall survival was 18.4 months (95% CI: 15.5 - 21.3). Therapy options after T-DM1 in a real-world setting seem to exhibit a relevant clinical efficacy, supporting the concept of continuous anti-HER2 treatments in the advanced therapy setting for breast cancer patients. Novel therapies are needed to improve the rather short median progression-free survival.
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http://dx.doi.org/10.1055/a-1286-2917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647719PMC
November 2020

Update Breast Cancer 2020 Part 4 - Advanced Breast Cancer.

Geburtshilfe Frauenheilkd 2020 Nov 6;80(11):1115-1122. Epub 2020 Nov 6.

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

Substances with good effectiveness that intervene in specific signalling pathways have been used increasingly in recent years in the treatment of patients with advanced breast cancer, and new therapies and approaches have now been added, which actually relate to quite specific changes, such as the treatment of patients with HR+/HER2 tumours with a mutation. The treatment of patients with a or mutation has also been improved by the introduction of PARP inhibitors. Attempts are now being made increasingly to extend treatment indications based on molecular patterns, to identify other patients who could benefit from a treatment and to integrate the newly established treatment methods in existing therapy sequences. This review articles summarises the latest information in this connection.
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http://dx.doi.org/10.1055/a-1270-7481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647717PMC
November 2020

Update Breast Cancer 2020 Part 3 - Early Breast Cancer.

Geburtshilfe Frauenheilkd 2020 Nov 6;80(11):1105-1114. Epub 2020 Nov 6.

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

The treatment of patients with early breast cancer has always been characterised by escalation by new therapies and de-escalation through identification of better treatment regimens or introduction of better tools to estimate prognosis. Efforts in some of these areas in the last few years have led to solid data. The results of the large studies of de-escalation through use of multi-gene tests are available, as are the results of some studies that investigated the new anti-HER2 substances T-DM1 and pertuzumab in the early treatment situation. Several large-scale studies examining the role of CDK4/6 inhibitors will soon be concluded so innovations can be anticipated in this area also. This review article will summarise and classify the results of the latest publications.
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http://dx.doi.org/10.1055/a-1270-7208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647721PMC
November 2020

Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial.

Breast Cancer Res 2020 10 23;22(1):111. Epub 2020 Oct 23.

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

Background: When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients.

Methods: A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety.

Results: No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively.

Conclusion: Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting.

Trial Registration: Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.
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http://dx.doi.org/10.1186/s13058-020-01348-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583247PMC
October 2020

Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

Cancers (Basel) 2020 Oct 17;12(10). Epub 2020 Oct 17.

Department of Gynecology and Obstetrics, Düsseldorf University Hospital, 40225 Düsseldorf, Germany.

The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment ( = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8-7.8); in second-line treatment, 7.7 months (95% CI: 2.8-11.0); in third-line, 3.4 months (95% CI: 2.3-not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2-NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.
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http://dx.doi.org/10.3390/cancers12103021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603111PMC
October 2020

Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk.

Am J Hum Genet 2020 11 5;107(5):837-848. Epub 2020 Oct 5.

Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong; Hong Kong Sanatorium and Hospital, Department of Pathology, Happy Valley, Hong Kong.

Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS was quantified using Cox regression analyses. We assessed PRS interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10 percentile and 20.5% at the 90 percentile of PRS. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
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http://dx.doi.org/10.1016/j.ajhg.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675034PMC
November 2020

Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer - Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany.

Breast 2020 Dec 29;54:88-95. Epub 2020 Aug 29.

Department of Gynecology and Obstetrics, Breast Center, and CCC Munich, Munich University Hospital, Germany.

Purpose: Treatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor-positive, HER2-negative (HR + HER2-) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported.

Methods: The PRAEGNANT registry was used to identify advanced HR + HER2- BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed.

Results: CDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy.

Conclusions: In clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET.
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http://dx.doi.org/10.1016/j.breast.2020.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509062PMC
December 2020

Interleukin 15 and Eotaxin correlate with the outcome of breast cancer patients vice versa independent of CTC status.

Arch Gynecol Obstet 2021 01 14;303(1):217-230. Epub 2020 Sep 14.

Department of Urology, Ludwig Maximilian University, Marchioninistraße 15, 81377, Munich, Germany.

Background: Circulating tumor cells (CTC) in the peripheral blood in women with breast cancer has been found to be an indicator of prognosis before the start of systemic treatment. The aim of this study is the assessment of specific cytokine profiles as markers for CTC involvement that could act as independent prognostic markers in terms of survival outcome for breast cancer patients.

Methods: Patients selected for this study were defined as women with breast cancer of the SUCCESS study. A total of 200 patients' sera were included in this study, 100 patients being positive for circulating tumor cells (CTC) and 100 patients being CTC negative. The matching criteria were histo-pathological grading, lymph node metastasis, hormone receptor status, TNM classification, and patient survival. Commercial ELISA with a multi cytokine/chemokine array was used to screen the sera for Interleukin 15 (IL-15) and eotaxin.

Results: Statistically significant concentrations were exposed for IL-15 levels regardless of the CTC-Status, lymph node involvement, or hormone receptor status. Significantly enhanced serum IL-15 concentrations were observed in those patients with worse overall survival (OS) and disease-free survival (DFS). Elevated serum concentrations of IL-15 significantly correlate with patients diagnosed with Grade 3 tumor and worse OS. In contrast, patients with a Grade 3 tumor with a favourable OS and DFS demonstrated significantly decreased IL-15 values. The CTC negative patient subgroup with a favourable OS and DFS, showed statistically significant elevated eotaxin values.

Conclusion: These findings suggest a potential functional interaction of increased IL-15 concentrations in the peripheral blood of patients with a worse OS and DFS, regardless of prognostic factors at primary diagnosis. The increased levels of the chemokine eotaxin in CTC negative patients and a favourable OS and DFS, on the other hand, suggest that the overexpression inhibits CTCs entering the peripheral blood, thus emphasizing a significant inhibition of circulation specific metastasis. To sum up, IL-15 could be used as an independent prognostic marker in terms of survival outcome for breast cancer patients and used as an early indicator to highlight high-risk patients and consequently the adjustment of cancer therapy strategies.
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http://dx.doi.org/10.1007/s00404-020-05793-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854415PMC
January 2021

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) and Epoetin (EPO) on Hematologic Toxicities and Quality of Life in Patients During Adjuvant Chemotherapy in Early Breast Cancer: Results From the Multi-Center Randomized ADEBAR Trial.

Clin Breast Cancer 2020 12 6;20(6):439-447. Epub 2020 Apr 6.

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

Background: Hematologic toxicities are one of the greatest challenges in adjuvant chemotherapy for breast cancer. This analysis of the ADEBAR trial aims to evaluate application and effect of granulocyte colony-stimulating factor (G-CSF) and epoetin alfa (EPO) on hematologic parameters and fatigue in patients with breast cancer during chemotherapy.

Patients And Methods: In the ADEBAR trial, 1493 patients with node-positive primary breast cancer were randomized to either 6 × 5-fluorouracil, epirubicin, and cyclophosphamide (FEC120) or 4 × epirubicin and cyclophosphamide followed by 4 × docetaxel (EC-DOC). Co-medication with G-CSF or EPO was applied to treat chemotherapy-induced leukopenia or anemia. Fatigue was assessed at baseline and after one-half of the chemotherapy.

Results: In total, 899 patients could be included in the analysis. There was no evidence for an association between leucocyte or hemoglobin levels and application of G-CSF and EPO in the preceding cycle, respectively. Hemoglobin levels (B = -0.41; P < .001) were affected by treatment regimen. Fatigue during chemotherapy was mostly affected by the level of fatigue before the start of chemotherapy (B = 0.41; P < .001). Patients with G-CSF application in the preceding cycle showed an increased fatigue score (B = 5.43; P = .02).

Conclusion: We showed that fatigue during adjuvant chemotherapy was mostly affected by the level of fatigue present before the start of chemotherapy. This result suggests that the level of fatigue before the start of treatment should be included as an important factor when deciding on type and toxicity of chemotherapy in early breast cancer.
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http://dx.doi.org/10.1016/j.clbc.2020.03.008DOI Listing
December 2020