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Abstract Breast cancer (BC) is a heterogeneous disease, traditionally classified by hormone receptor and HER2 (human epidermal growth factor receptor 2) status. HER2-low, characterized by low HER2 expression without gene amplification, recently gained attention. While new therapies are promising, its clinical significance remains unclear. We analysed 241,510 BC patients diagnosed between 2000 and 2020 in Germany using data from the German Cancer Registry Group. HER2 status was determined using immunohistochemistry and fluorescence in situ hybridization results, and patients were classified as HER2-positive, HER2-low or HER2-zero. Clinical features, chemosensitivity and long-term outcomes - metastasis-free survival (MFS), recurrence-free survival (RFS), and overall survival (OS) - were analysed using Cox models. HER2-low comprised 42% of female and 47% of male patients, predominantly hormone receptor positive. Metastatic patterns in HER2-low and HER2-zero were similar but differed from HER2-positive, which showed more liver metastasis and multiple metastatic sites. HER2-positive showed worse MFS, RFS, and OS than HER2-zero and HER2-low subtypes. Pathological complete response (pCR) rates after neoadjuvant chemotherapy were highest in HER2-positive. HER2-low has higher hormone receptor positivity, distinguishing it from HER2-zero. While metastatic behaviour, treatment and long-term response in HER2-low were comparable to HER2-zero, the hormone receptor status seems to play a critical role in these outcomes.

Abstract Background The medical field is in the midst of a massive expansion in telemedical services. However, it is not possible to say to what extent telemedical offerings can be designed to meet needs in the German healthcare system. This study provides insights into demand-oriented care using telemedical services for gynecological patients. Methods A total of 262 patients who received systemic therapy for gynecological oncology were surveyed anonymously using a questionnaire regarding their acceptance of telemedicine from February 2021 to April 2021. Results Insufficient computer skills were associated with less acceptance of telemedicine treatment by gynecological oncology patients and presented a barrier. However, the patient’s level of education was not related to the level of acceptance. Long travel distances from medical facilities and some types of patient occupations significantly increased the acceptance of telemedicine services. A high level of education, on the other hand, was not associated with the approval of telemedical approaches. Long journeys and work commitments increased the acceptance of telemedical visits. Conclusions The results of this study show that the factors investigated have an influence on the acceptance of telemedical offerings by patients. Barriers such as insufficient computer skills must be taken into account when implementing telemedicine services. Telemedicine can provide physical and economic relief for patients if telemedical planning is tailored to their needs.

There is a lack of evidence regarding the clinical impact of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT, hereinafter referred to as PET/CT), especially regarding management changes and their link to overall survival. We analyzed 52 PET/CTs in 47 stage I-IV breast cancer patients, selected from a prospective oncological PET/CT registry. Indications for PET/CT were primary staging (n = 15), restaging (n = 17), and suspected recurrence (n = 20). PET/CT-induced management changes were categorized as major or minor. PET/CT-induced management changes in 41 of 52 scans (78.8%; 38 of 47 patients (80.9%)), of which major changes were suggested in 18 of 52 scans (34.6%, 17 of 47 patients, 36.2%). PET/CT downstaged 6 of 15 primary staging patients, excluding distant metastases. Major management changes were documented in 3 of 17 restaging exams. PET/CT ruled out clinically suspected recurrence in 6 of 20 cases and confirmed it in 11 of 20. In three cases, locoregional recurrence had already been diagnosed via biopsy. In 30 of 52 exams, additional diagnostic tests were avoided, of which 13 were invasive. PET/CT-based management changes resulted in a 5-year survival rate of 72.3% for the whole study group, 93.3% for the staging group, 53.8% for the restaging group, and 68.4% for the recurrence group. This study shows that PET/CT significantly impacts clinical management decisions in breast cancer patients in different clinical scenarios, potentially determining the patient’s tumor stage as the basis for further therapy more reliably and by avoiding unnecessary diagnostic tests.

BackgroundOne in eight women is diagnosed with breast cancer in the course of their life. As systematic palliative treatment has only a limited effect on survival rates, the concept of health-related quality of life (HRQoL) was developed for measurement of patient-centered outcomes. Various studies have already demonstrated the reliability of paper-based patient-reported outcome (pPRO) and electronic patient-reported outcome (ePRO) surveys and that the 2 means of assessment are equally valid. ObjectiveThe aim of this study was to analyze the acceptance and evaluation of a tablet-based ePRO app for breast cancer patients and to examine its suitability, effort, and difficulty in the context of HRQoL and sociodemographic factors. MethodsOverall, 106 women with adjuvant or advanced breast cancer were included in a 2-center study at 2 major university hospitals in Germany. Patients were asked to answer HRQoL and PRO questionnaires both on a tablet on-site using a specific eHealth assessment website and on paper. The suitability, effort, and difficulty of the app and self-reported technical skills were also assessed. Only the results of the electronically acquired data are presented here. The results of the reliability of the pPRO data have already been published elsewhere. ResultsPatients regarded the ePRO assessment as more suitable (80/106, 75.5%), less stressful (73/106, 68.9%), and less difficult (69/106, 65.1%) than pPRO. The majority of patients stated that ePRO assessment improves health care in hospitals (87/106, 82.1%). However, evaluation of ePROs depended on the level of education (P=.003) in the dimensions of effort and difficulty (regression analysis). The app was rated highly in all categories. HRQoL data and therapy setting did not show significant correlations with the app’s evaluation parameters. ConclusionsThe results indicate that ePRO surveys are feasible for measuring HRQoL in breast cancer patients and that those patients prefer ePRO assessment to pPRO assessment. It can also be seen that patients consider ePRO assessment to improve hospital health care. However, studies with larger numbers of patients are needed to develop apps that address the needs of patients with lower levels of education and technical skills.

BackgroundHealth-related quality of life (HRQoL) is used to evaluate the treatment of metastatic breast cancer. In a long-term therapy setting, HRQoL can be used as an important benchmark for treatment success. With the help of digital apps, HRQoL monitoring can be extended to more remote areas and be administered on a more frequent basis. ObjectiveThis study aims to evaluate 3 common HRQoL questionnaires in metastasized breast cancer in terms of TTD in a digital, web-based setting. We further aim to examine the development of the HRQoL in different systemic treatment groups in each of these evaluation instruments. MethodsA total of 192 patients with metastatic breast cancer were analyzed in this bicentric prospective online cohort study at two German university hospitals. Patients completed questionnaires on HRQoL (EuroQol Visual Analog Scale [EQ-VAS], EuroQol 5 Dimension 5 Level [EQ-5D-5L], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 item [EORTC QLQ-C30]) via an online platform over a 6-month period. Treatment schedules and medical history were retrieved from medical records. Unadjusted Cox regression analysis on treatment-related factors was performed. We conducted subgroup analyses in regard to TTD events between different treatments. ResultsThe EQ-VAS showed a higher rate of deterioration after 8 weeks (84/179, 46.9%) than the EQ-5D-5L (47/163, 28.8%) and EORTC QLQ-C30 (65/176, 36.9%). Unadjusted Cox regression revealed significant connections between known metastases in the liver (P=.03, HR 1.64, 95% CI 1.06-2.52) and pleura (P=.04, HR 0.42, 95% CI 0.18-0.96) in the EQ-VAS. Significant relations between EQ-VAS events and single EQ-5D-5L items and the EQ-5D-5L summary score were demonstrated. All treatment groups significantly differed from the CDK4/6 inhibition subgroup in the EQ-VAS. ConclusionsCompared to the EQ-5D-5L and QLQ-C30, the EQ-VAS showed a higher rate of deterioration after 8 weeks. Significant connections to certain metastatic locations were only detected in the EQ-VAS. The EQ-VAS is capable of reflecting the distinctive HRQoL profiles of different systemic treatments as well as the different aspects of HRQoL presented in the EQ-5D-5L. TTD with the EQ-VAS is an adequate mean of examining longitudinal development of HRQoL among breast cancer patients.

Background The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level.Methods Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing.Results The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference.Conclusion Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org.

Previous publications suggest a reduction in the ovarian reserve following ovarian surgery. The influence of the underlying disease, histology, size of the ovarian cyst and type of procedure remains unclear. The aim of this study was to investigate the influence of an ovarian operation on the ovarian reserve, based on the anti-Müllerian hormone levels. The anti-Müllerian hormone values were determined by means of a standardized enzyme-linked immunosorbent assay. In total, 52 patients with one or more ovarian cysts of different histologic entities treated at the Department of Women’s Health at the Women’s University Hospital in Tübingen were included in the study. Anti-Müllerian hormone was determined before and after surgery. The patients were 28 (range = 18–40) years old on average. There was a statistically significant decrease in anti-Müllerian hormone from 3.94 ± 3.18 to 3.14 ± 2.57 ng/mL (p = 0.001). In 80.8%, the cysts were unilateral, and in over 90.4%, a complete cyst extirpation was performed. A statistically significant reduction was seen in follicular cysts (4.72 ± 3.84 to 3.76 ± 2.91 ng/mL; p = 0.039) and endometriosis cysts (2.55 ± 1.87 to 1.72 ± 1.39 ng/mL; p = 0.024). Also, the size of the cysts had an influence on the ovarian reserve, only larger ovarian cysts with a diameter of 5 cm or more showed a statistically significant reduction in anti-Müllerian hormone. Our data showed a significant decrease in anti-Müllerian hormone levels after surgery on the ovaries. If this results in a long-term reduced ovarian reserve or is merely a short-term reaction to the procedure needs to be clarified. However, concerning young women, the indication of surgery should be given cautiously as—at least temporarily—a reduction in the ovarian reserve can occur.