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Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of an acute inflammatory versus a chronic inflammatory interleukin signature using microarray-based gene expression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, and CD20) and immune checkpoints (PD-1) were also evaluated. This study investigated the prognostic significance of an acute inflammatory IL signature (IL-12, IL-21, and IFN-γ) and a chronic inflammatory IL signature (IL-4, IL-5, IL-10, IL-13, IL-17, and CXCL1) for metastasis-free survival (MFS) using Kaplan–Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman–Rho correlation coefficient. Kaplan–Meier curves revealed that the prognostic significance of the acute inflammatory IL signature was specifically pronounced in the basal-like subtype (p = 0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290–0.741; p = 0.001). A higher expression of the acute inflammatory IL signature was associated with longer MFS. The chronic inflammatory IL signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p = 0.034). Strong correlations were found between the acute inflammatory IL signature and CD8 expression (ρ = 0.391; p < 0.001) and between the chronic inflammatory IL signature and PD-1 expression (ρ = 0.627; p < 0.001). This study highlights the complex interaction between acute and chronic inflammatory interleukins in breast cancer progression and prognosis. These findings provide insight into the prognostic relevance of interleukin expression patterns in breast cancer and may inform future therapeutic strategies targeting the immune–inflammatory axis. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) poses a challenge in establishing new treatment strategies and identifying new prognostic and predictive markers due to the extensive genetic heterogeneity of BC. Very few studies have investigated the impact of mRNA expression of these genes on the survival of BC patients. Methods: We examined the impact of the mRNA expression of breast cancer gene type 1 (BRCA1), breast cancer gene type 2 (BRCA2), and partner and localizer of BRCA2 (PALB2) on the metastasis-free survival (MFS) of patients with early BC using microarray gene expression analysis. Results: The study was performed in a cohort of 461 patients with a median age of 62 years at initial diagnosis. The median follow-up time was 147 months. We could show that the lower expression of BRCA1 and BRCA2 is significantly associated with longer MFS (p < 0.050). On the contrary, the lower expression of PALB2 was correlated with a shorter MFS (p = 0.049). Subgroup survival analysis identified the prognostic influence of mRNA expression for BRCA1 among patients with luminal-B-like BC and for BRCA2 and PALB2 in the subset of patients with luminal-A-like BC (p < 0.050). Conclusions: According to our observations, BRCA1, BRCA2, and PALB2 expression might become valuable biomarkers of disease progression. [ABSTRACT FROM AUTHOR]

Simple Summary: The implementation of immune checkpoint inhibitors into the therapeutic armamentarium for many solid tumors has transformed the treatment landscape of gynecological malignancies. The mechanism of action of immune checkpoint inhibitors is to increase the body's own tumor-directed T-cell response, which can, however, lead to a new spectrum of immunotherapy-associated adverse events (irAEs). In the present study, we retrospectively analyzed the incidence, diagnosis, and management of irAEs in patients with gynecologic malignancies who received immune checkpoint inhibitors and discussed our findings in the context of the recent literature. Our results emphasize the need for proactive monitoring and tailored management strategies to optimize the safety and efficacy of immunotherapy in cancer patients. Background: Immune checkpoint inhibitors (ICIs) have emerged as an essential therapeutic approach in treating many solid tumors. ICIs enhance the body's anti-tumor T-cell activity, resulting in a novel spectrum of immunotherapy-related side effects. This novel spectrum of adverse events differs significantly from the side effects of conventional chemotherapy. It, therefore, requires special attention in the diagnosis and management of immunotherapy-related adverse events (irAEs). The present study aimed to retrospectively analyze the incidence, diagnosis, and management of irAEs in patients with gynecologic malignancies who received ICIs and to discuss these findings in the context of the recent literature. Methods: In the present retrospective overview, we evaluated patients with gynecologic malignancies (breast, endometrial, cervical, ovarian) who received ICIs with regard to the incidence, type, and time to onset of irAEs. A total of 61 patients treated at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany, between 2018 and 2023 were included in the analysis. Results: A total of 32.8% of patients developed an irAE of any grade or type. The median time to irAE was 24 weeks. The most frequently observed irAEs were grade 1 (20%) or 2 (35%). Immunotherapy-related grade 3 or 4 adverse events occurred in 45% of patients (40% grade 3, 5% grade 4). The most common type of irAE in our cohort was hypothyroidism, followed by hepatitis and colitis. Cox regression analysis identified the duration of ICI therapy as the only significant factor influencing the incidence of irAEs (p = 0.004). Conclusion: The broad spectrum of irAEs and the onset time of irAEs are important challenges of therapy with ICIs, requiring proactive monitoring and tailored management strategies to optimize the safety and efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar cancer carries a favourable prognosis in early stages. However, therapeutic options for advanced or recurrent cases are limited despite a variety of therapeutic modalities, such as extensive surgical resection, chemotherapy, and radiotherapy. The most important emerging treatment modalities are immune checkpoint inhibitors. This systematic review and meta-analysis aims to assess the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, in women with advanced vulvar cancer. Materials and methods: Following a comprehensive search, review, and appraisal, two relevant single-arm studies were included. Meta-analysis was conducted using R4.3.0 software and RStudio 2023.03.0, presenting the overall effect size with a 95% confidence interval. Heterogeneity was assessed using I² and the Cochrane Q Χ² statistics. Results: Out of 154 studies screened for eligibility, two single-arm studies involving 119 patients receiving pembrolizumab for advanced vulvar cancer were included. The pooled objective response rate (ORR) was overall 10% (95% CI: 0.00-0.84) and 9% (95% CI: 0.00-0.89) in the PD-L1 positive subgroup. In the intention-to-treat (ITT) population, 31% (95% CI: 0.04-0.85) exhibited any clinical benefit (complete response, partial response, or stable disease). In the ITT population at six months, progression-free survival (PFS) was 19% (95% CI: 0.01-0.82), and overall survival (OS) was 48% (95% CI: 0.08-0.90). At 12 months, PFS decreased to 9% (95% CI: 0.00-0.85), and OS was 33% (95% CI: 0.04-0.85). No statistically significant heterogeneity was observed in PFS and OS analyses. Discussion and conclusion: This study suggests that one-third of women with advanced or recurrent vulvar cancer may, without the influence of PD-L1 status, benefit from pembrolizumab treatment despite a decline in both PFS and OS at 12 months. These findings provide support for considering pembrolizumab in the treatment paradigm for this specific subset of cancer patients. [ABSTRACT FROM AUTHOR]

Background: Pelvic organ prolapse constitutes a prevalent condition associated with a considerable impact on the quality of life. The utilization of transvaginal mesh surgery for managing POP has been a subject of extensive debate. Globally, trends in TVM surgery experienced significant shifts subsequent to warnings issued by the FDA. Methods: This study aims to explore temporal patterns in transvaginal mesh surgery in the German healthcare system. A comprehensive analysis was conducted on in-patient data from the German Federal Statistical Office spanning 2006 to 2021. A total of 1,150,811 operations, each associated with specific codes, were incorporated into the study. Linear regression analysis was employed to delineate discernible trends. Results: The trends in transvaginal mesh surgery within the anterior compartment exhibited relative stability (p = 0.147); however, a significant decline was noted in all other compartments (posterior: p < 0.001, enterocele surgery: p < 0.001). A subtle increasing trend was observed for uterine-preserving transvaginal mesh surgery (p = 0.045). Conclusion: Surgical trends over the specified timeframe demonstrate how POP management has evolved globally. Notably, despite observed fluctuations, transvaginal mesh surgery remains a viable option, particularly for specific cases with a high risk of relapse and contraindications to alternative surgical approaches. [ABSTRACT FROM AUTHOR]

Due to a higher mutational load, triple-negative breast cancer (TNBC) is characterized by a higher immunogenicity compared to other subtypes. In this context, we analyzed the prognostic significance of tumor-infiltrating plasma cells in a cohort of 107 triple-negative breast cancer patients. Tumor-infiltrating plasma cells were analyzed via immunohistochemistry using the plasma cell markers CD38 and IgκC. The prognostic impact of the CD38 and IgκC expression was evaluated using the Kaplan–Meier plots and Cox regression analyses. A Spearman-Rho correlation coefficient was used to evaluate a possible association between plasma cell infiltration and the BRCA mutation status. The study cohort consisted of 107 patients with early-stage TNBC, who were treated between 2009 and 2016 at the Department of Gynecology and Obstetrics, University Medical Center Mainz, Germany. The median follow-up was five years. The Kaplan–Meier survival analysis showed that higher tumor infiltration with CD38-positive plasma cells was associated with significantly longer metastasis-free survival (MFS) (p = 0.039 Log Rank). In the multivariate Cox regression analysis for metastasis-free survival, in which additional clinicopathological factors (age, tumor size, nodal status, and grading) were considered, CD38 was identified as an independent prognostic factor within the analyzed cohort (HR 0.438, 95% CI 0.195–0.983; p = 0.045). In addition to the CD38 expression, the nodal status was also identified as an independent prognostic factor in multivariate Cox regression. Regarding the IgκC expression, a higher IgκC expression was shown to be associated with a better outcome, although this effect was not statistically significant. Furthermore, we were able to show a significant correlation between plasma cell infiltration and the BRCA mutation status. A favorable prognostic significance of tumor-infiltrating plasma cells could be demonstrated in triple-negative breast cancer immunohistochemically analyzed for the CD38 and IgκC expression. CD38 was identified as an independent prognostic factor via multivariate Cox regression. [ABSTRACT FROM AUTHOR]

Background: Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel node (SN) procedure can be offered in well-selected patients with early vulvar cancer. This study aimed to assess current management practices with respect to the sentinel node procedure in women with early vulvar cancer in Germany. Methods: A Web-based survey was conducted. Questionnaires were e-mailed to 612 gynecology departments. Data were summarized as frequencies and analyzed using the chi-square test. Results: A total of 222 hospitals (36.27%) responded to the invitation to participate. Among the responders, 9.5% did not offer the SN procedure. However, 79.5% evaluated SNs by ultrastaging. In vulvar cancer of the midline with unilateral localized positive SN, 49.1% and 48.6% of respondents, respectively, would perform ipsilateral or bilateral inguinal lymph node dissection. Repeat SN procedure was performed by 16.2% of respondents. For isolated tumor cells (ITCs) or micrometastases, 28.1% and 60.5% of respondents, respectively, would perform inguinal lymph node dissection, whereas 19.3% and 23.8%, respectively, would opt for radiation without further surgical intervention. Notably, 50.9% of respondents would not initiate any further therapy and 15.1% would opt for expectant management. Conclusions: The majority of German hospitals implement the SN procedure. However, only 79.5% of respondents performed ultrastaging and only 28.1% were aware that ITC may affect survival in vulvar cancer. There is a need to ensure that the management of vulvar cancer follows the latest recommendations and clinical evidence. Deviations from state-of-the-art management should only be after a detailed discussion with the concerned patient. [ABSTRACT FROM AUTHOR]

Simple Summary: Novel antibody-drug conjugates (ADCs) show efficacy in advanced breast cancer with low HER2 levels. Little is known about the discordance of low HER2 levels between the primary tumor and distant metastases. The clinical relevance of discordance between the primary tumor and metastases prompted us to investigate the differences in HER2 expression between primary tumors and distant metastases, particularly in the HER2-negative (HER2-low and HER2-zero) primary breast cancer cohort. Our results show a relevant discordance of HER2-low status between primary tumors and their corresponding distant metastases. We examined differences in HER2 expression between primary tumors and distant metastases, particularly within the HER2-negative primary breast cancer cohort (HER2-low and HER2-zero). The retrospective study included 191 consecutive paired samples of primary breast cancer and distant metastases diagnosed between 1995 and 2019. HER2-negative samples were divided into HER2-zero (immunohistochemistry [IHC] score 0) and HER2-low (IHC score 1+ or 2+/in situ hybridization [ISH]-negative). The main objective was to analyze the discordance rate between matched primary and metastatic samples, focusing on the site of distant metastasis, molecular subtype, and de novo metastatic breast cancer. The relationship was determined by cross-tabulation and calculation of Cohen′s Kappa coefficient. The final study cohort included 148 paired samples. The largest proportion in the HER2-negative cohort was HER2-low [primary tumor 61.4% (n = 78), metastatic samples 73.5% (n = 86)]. The discordance rate between the HER2 status of primary tumors and corresponding distant metastases was 49.6% (n = 63) (Kappa −0.003, 95%CI −0.15–0.15). Development of a HER2-low phenotype occurred most frequently (n = 52, 40.9%), mostly with a switch from HER2-zero to HER2-low (n = 34, 26.8%). Relevant HER2 discordance rates were observed between different metastatic sites and molecular subtypes. Primary metastatic breast cancer had a significantly lower HER2 discordance rate than secondary metastatic breast cancer [30.2% (Kappa 0.48, 95%CI 0.27–0.69) versus 50.5% (Kappa 0.14, 95% CI −0.03–0.32)]. This highlights the importance of evaluating potentially therapy-relevant discordance rates between a primary tumor and corresponding distant metastases. [ABSTRACT FROM AUTHOR]

(1) Background: Endometriosis is a frequent chronic pain condition in women of fertile age. Pain management with analgesics is frequently used by women with endometriosis. During the COVID-19 pandemic, access to health services was temporarily restricted in various countries for persons without serious conditions, resulting in increased physical and mental health issues. The present study was conducted in order to assess the risk factors predicting increased analgesic intake by women with endometriosis during the COVID-19 pandemic. (2) Methods: The increased intake of over-the-counter (OTC) and prescription-only (PO) analgesics was assessed with an anonymous online questionnaire, along with demographic, pandemic-specific, disease-specific, and mental health characteristics. Anxiety and depression were assessed with the Generalized Anxiety Disorder Scale (GAD-2) and the Patient Health Questionnaire for Depression (PHQ-2), respectively. Pain-induced disability was assessed with the pain-induced disability index (PDI). (3) Results: A high educational level (OR 2.719; 95% CI 1.137–6.501; p = 0.025) and being at higher risk for depressive disorders, as measured by PHQ-2 ≥ 3 (OR 2.398; 95% CI 1.055–5.450; p = 0.037), were independent risk factors for an increased intake of OTC analgesics. Current global pain-induced disability (OR 1.030; 95% CI 1.007–1.054; p = 0.010) was identified as a risk factor for an increased intake of PO pain medication. The degree of reduction in social support and in social networks were independent predictors of an increased intake of PO analgesics in a univariate logistic regression analysis, but lost significance when adjusted for additional possible influencing factors. (4) Conclusions: In this population, an increased intake of OTC analgesics was related to a higher educational level and having a depressive disorder, while a higher pain-induced disability was an independent risk factor for an increased intake of PO analgesics. Pandemic-specific factors did not significantly and independently influence an increased intake of analgesics in women with endometriosis during the first wave of the COVID-19 pandemic in Germany. Healthcare providers should be aware of the possible factors related to increased analgesic use in women with endometriosis in order to identify persons at risk for the misuse of pain medication and to prevent potential adverse effects. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibodies against PD-1 or PD-L1 have been established in clinical practice for the treatment of both early and advanced/metastatic triple-negative breast cancer. Beyond the established immune checkpoints (ICPs) (PD-1 and CTLA-4), additional ICPs, such as lymphocyte activation gene-3 (LAG-3), are subject of current research. In the present retrospective gene-expression analysis, we evaluated the prognostic significance of LAG-3 in 461 patients with early breast cancer. In addition, we examined whether there was a correlation between the different ICP and CD8 expressions. Methods: Using microarray-based gene-expression analysis, we examined the prognostic significance of LAG-3 mRNA expression for metastasis-free survival (MFS) in the whole cohort of 461 breast cancer patients and among different molecular subtypes. Correlations were analyzed using Spearman's rho correlation coefficient. Results: In the whole cohort, LAG-3 expression had no significant impact on MFS (p = 0.712, log-rank). In the subgroup analyses, there was a trend that a higher LAG-3 expression was associated with a favorable outcome in the luminal B (p = 0.217), basal-like (p = 0.370) and HER2 (p = 0.089) subtypes, although significance was not reached. In contrast, in a multivariate Cox regression analysis, adjusted for age, tumor size, axillary nodal status, histological grade of differentiation and proliferation marker Ki-67, LAG-3 showed a significant influence on MFS (HR 0.574; 95% CI 0.369–0.894; p = 0.014). High LAG-3 significantly correlated with CD8 (ρ = 0.571; p < 0.001). Conclusions: LAG-3 expression had an independent impact on MFS. In addition to PD-1 and PD-L1, further immune checkpoints, such as LAG-3, could serve as therapeutic targets in breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic has affected individuals' and society's physical and psychological well-being. The study was conducted in order to assess the predictors for health-related worries during the COVID-19 pandemic in vulnerable populations. Patients and Methods: A cross-sectional web-based survey of women who had a higher risk of developing breast cancer (BC) or ovarian cancer (OC) was conducted, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire was designed for this study to assess health-related worries. The PHQ-4 questionnaire was used to evaluate mental health, and the Brief Resilience Scale (BRS) questionnaire was employed to investigate resilience. Results: History of BC or OC was recognized as an independent significant risk factor for worries regarding being more susceptible to a more severe course of COVID-19 disease (OR 3.593; 95% CI 1.030– 12.536; p = 0.045). High scores in the BRS questionnaire were negatively correlated with health-related worries, such as an increased risk for occurrence of BC or OC (OR 0.332; 95% CI 0.118– 0.933; p = 0.37) or worsening of oncological outcome as a result of an infection with the SARS-CoV-2 virus (OR 0.330; 95% I 0.114– 0.956; p = 0.041). Conclusion: The obtained findings determined resilience as an independent and potent protective parameter in terms of health-related concerns in women at high risk for BC and OC. The results may assist in identifying women at risk for health-related concerns during adverse life events, allowing healthcare providers to respond fast and according to the patients´ needs. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a multifaceted chronic pain disorder that can have an impact on both physical and mental health. Women suffering from chronic pain may be more susceptible to various health disorders, especially during adversity, such as the COVID-19 pandemic. Previous research has identified resilience as a mediator between internal or external stressors and well-being. Methods: An online survey was conducted during the first wave of the COVID-19 pandemic in Germany through patient support groups of women with endometriosis. The Brief Resilience Score (BRS) was employed to evaluate resilience, while the PHQ-4 questionnaire was used to assess self-reported mental health. Univariate and multivariate logistic regression analyses were applied to determine resilience's independent risk and protective parameters. Results: High educational level was found to be an independent supportive moderator of high resilience in women with a resilience score greater than the study population's median (BRS > 2.66; OR 2.715; 95% CI 1.472–5.007; p = 0.001) but not in women in the highest resilience score quartile (BRS > 3.33). A decrease in perceived social support was detected to be the most powerful independent risk factor for low resilience: OR 0.541, 95% CI 0.307–0.952, p = 0.033 for predicting BRS > 2.66, and OR 0.397, 95% CI 0.189–0.832, p = 0.014 for predicting scores > 3.33 on the BRS scale. A high burden of mental health symptoms, as measured by the PHQ-4 scale, was negatively associated with resilience. Conclusions: Satisfying social support and good mental health were shown to be key resources for resilience. The results of this study may assist in the identification of women at risk for low resilience and the development of resilience-building strategies in patients with endometriosis. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic pain condition in premenopausal women. Pain is mainly characterized by pain intensity and may induce disability in all areas of daily life. Nevertheless, pain is influenced by emotional and social factors as well. Social distancing measures or quarantine, as reaction to rapidly rising infections with the COVID-19 virus due to the SARS-CoV-2 pandemic, were implemented across Europe to prevent the spread of the virus and social distancing measures were imposed by the German government by beginning of March 2020 with initiation of the lockdown by the end of March 2020. The objective of this study was to assess, how social distancing measures during the lockdown impacted the various aspects of pain perception in a group of chronic pain patients, such as women suffering from endometriosis. Methods: Between 6th to 27th April 2020, an online questionnaire was activated at internet platforms of endometriosis patients support groups. Participants were asked retrospectively at one time point about their visual pain intensity measured by the visual analogue scale (VAS) and pain disability via pain disability index (PDI) prior to initiation of social distancing measures in Germany (VASP, PDIP), as well as the pain intensity and pain disability since implementation of social distancing measures (VASI, PDII). Differences of VAS and PDI previous and after implementation of social distancing measures were displayed as ΔVAS and ΔPDI. Pain experience and social support were assessed by a 5-point Likert scale. Results: 285 participants completed at least one question regarding pain intensity, disability, pain experience or social support. Dysmenorrhea, the symptom with the highest level of pain assessed by VAS, decreased significantly during the SARS-CoV-2 pandemic compared to the time period prior to social isolation (45.30% respondents experienced improvemenet vs 40.50% who experienced worsening; p = 0.025). The global physical impairment improved significantly (improvement of pain induced disability in 48.20% vs 40.90% with worsening of pain symptoms; p = 0.032) after the implementation of social distancing measures. Pain experience was negatively affected by social distancing measures, since frequency of pain awareness increased in 43.6% (p<0.001) of participants and 30.0% (p<0.001) more participants experienced pain as a threat. Verbalization of pain experience was reduced in 36.6% (p = 0.001) of participants and 14.6% (p = 0.91), 21.9% (p<0.001) and 31.5% (p<0.001) of participants reported less social support from their partner, family and friends. Conclusions: Physical pain and disability on one hand and emotional and social pain experience on the other were differentially affected by the emerged emotional, social and health care constraints related to the SARS-CoV-2 pandemic. [ABSTRACT FROM AUTHOR]

Background: Only little is known about the psychosocial aspects of breast cancer patients after mastectomy with immediate versus delayed breast reconstruction. Methods: We systematically screened PubMed using the following key words: mastectomy, immediate vs. delayed reconstruction, psychosocial aspects and quality of life. To highlight different psychological outcomes, studies were categorized into those describing: anxiety, depression, body image and satisfaction with the surgical outcome. We also compared patients after mastectomy alone with those undergoing immediate or delayed reconstruction. Results: Methodologies and psychological outcomes varied among the identified studies, making it difficult to compare results. There are contradictory outcomes concerning the psychosocial aspects of breast cancer patients after mastectomy alone compared with those who underwent an immediate or delayed reconstruction following mastectomy. Some studies show that immediate reconstruction after mastectomy had a positive impact on patients' psychological well-being. In contrast, other studies indicated that in the long-term view the compared patient groups were very similar concerning psychosocial aspects. Conclusion: Analyzing different aspects of psychosocial well-being after breast cancer surgery, there might be an advantage in choosing immediate reconstruction, if oncological safety allows it. [ABSTRACT FROM AUTHOR]

Objectives: To identify patient-approved contingency measures for protection of patients and healthcare workers (HCWs) from COVID-19 infection and to use these findings to improve staff's preparedness to cope with the course of this pandemic or similar situations., Methods Design, Setting, Participants, Interventions: We conducted a cross-sectional, web-based survey of women with an increased risk of breast or ovarian cancer, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire, developed for this study, was used to assess expectations and opinions about preventive measures within medical institutions., Results: Sixty-four (71.9%) of the 89 potential participants responded to at least one question regarding contingency measures within medical institutions. Approximately 37% of the respondents preferred having information about their facility's hygiene protocols before appointment; 57.8% of the respondents endorsed regular SARS-CoV-2 testing of patients prior to medical appointments and 95.3% endorsed regular testing of HCWs. Additionally, 84.4% of the respondents supported HCWs' use of surgical masks and 68.8% supported HCWs' use of masks with greater protection. Notably, 75.0% of the respondents advocated for the presence of a significant other during medical consultations; 71.9% approved the use of telemedicine and 93.8% endorsed changes in appointment practices to enable social distancing. No significant associations were found between respondents' sociodemographic, disease-specific or pandemic-specific factors and their opinions on hygiene precautions., Conclusions: Patients at high risk of infection or severe course of COVID-19 approve strict contingency measures designed to lower the transmission of COVID-19 in medical facilities. Moreover, vulnerable groups may profit from contingency plans in healthcare facilities in order to follow preventive measures, avoid diagnostic delay or avoid worsening of pre-existing conditions. However, they also value the presence of a significant other during medical consultations and procedures., Competing Interests: Competing interests: RS: honoraria: Roche Pharma, AstraZeneca, streamedup!. MS: received personal fees from AstraZeneca, BioNTech, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Roche and Seagen; institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre and Roche; and travel reimbursement from Pfizer and Roche. In addition, MS is named an inventor on patent EP 2390370 B1 and granted patent EP 2951317 B1. AH: honoraria: AstraZeneca, Celegene, MedConcept, med update, medicultus, Pfizer, ProMedicis, Softconsult, Roche Pharma, streamedup!, Tesaro Bio Germany and LEO Pharma; Ad Board: PharmaMar, ProMedicis, Roche Pharma, Tesaro Bio Germany, AstraZeneca, LEO Pharma, MSD and Sharp & Dohme., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT., Patients and Methods: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts ( n = 619)., Results: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer., Conclusions: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts., (©2021 American Association for Cancer Research.)