OBJECTIVES:Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age and is associated with significant metabolic, reproductive, and psychological morbidity. Although international evidence-based guidelines exist, patient reports continue to indicate unmet needs, particularly in areas that most affect quality of life. The primary objective of this study was to assess PCOS-related knowledge, as well as general practitioners' (GPs) perceptions and interdisciplinary communication practices. A secondary objective was to examine whether identified knowledge gaps among GPs align with symptom domains reported by patients as most bothersome. DESIGN:This study employed a cross-sectional survey design targeting practicing GPs. Quantitative findings were descriptively analyzed and contextualized using published data from an independent, large-scale patient survey. Participants/Materials: A total of 918 GPs practicing in the federal state of Hesse, Germany, were invited to participate. The final analytical sample comprised 118 GPs who completed the survey. The GP questionnaire included demographic and professional characteristics as well as a 21-item knowledge assessment derived from the 2018 International PCOS Guideline. To contextualize GP findings, data from a published patient survey including 1,926 individuals with PCOS were used to identify patient-prioritized symptom domains. SETTING:The study was conducted in primary care settings across Hesse, Germany. METHODS:The GP survey assessed awareness of PCOS prevalence, familiarity with guideline recommendations, perceived relevance of guidelines to daily practice, and interdisciplinary collaboration, particularly with gynecologists. Knowledge accuracy scores were calculated as the percentage of correct responses across the 21 items. Subgroup analyses explored associations between GP characteristics and knowledge levels. Published patient survey data were used to determine symptom burden and domains perceived as most distressing, allowing comparison with GP knowledge gaps. RESULTS:A total of 93.2% of GPs estimated PCOS prevalence in their practice below 5% and 69.5% considered the International PCOS Guideline irrelevant to routine practice. PCOS-related knowledge among participants showed a mean accuracy of 54.6% (95% CI: 50.4-58.8) across all domains, with the lowest scores in reproductive aspects (45.5%, 95% CI: 40.6-50.4) and hyperandrogenism (43.7%, 95% CI: 38.7-48.7). Notably, cosmetic manifestations of hyperandrogenism were identified by patients as among the most burdensome symptoms. Furthermore, 45.8% of GPs reported suboptimal communication with gynecologists, highlighting deficiencies in interdisciplinary care pathways. LIMITATIONS:Limitations include a low response rate with potential nonresponse bias, the newly developed questionnaire without formal psychometric validation, and reliance on self-reported data. In addition, variation in patient populations across practices and the lack of linkage between physician responses and patient outcomes may limit generalizability. CONCLUSIONS:PCOS-related knowledge gaps among GPs are most pronounced in clinical domains that patients perceive as most distressing, highlighting a critical mismatch between care provision and patient needs. These findings underscore the necessity for targeted educational interventions, improved dissemination and implementation of PCOS guidelines in primary care, and strengthened interdisciplinary collaboration to enhance patient-centered PCOS management.

Abstract Background A structured risk assessment of patients with validated and evidence-based tools can help to identify modifiable factors before major surgeries. The Protego Maxima trial investigated the value of a new digitized risk assessment tool that combines tools which can be easily used and implemented in the clinical workflow by doctors and qualified medical staff. The hypothesis was that the structured assessment and risk-grouping is predictive of short-term surgical quality reflected by complications and overall survival. Methods The Protego Maxima Trial was a prospective cohort analysis of patients undergoing major surgery (visceral, thoracic, urology, vascular and gynecologic surgeries) as key inclusion criterion and the absence of an acute or acute on chronically decompensated pulmo-cardiovascular decompensation. Patients were risk-scored with the software (The Prehab App) that includes a battery of evidence-based risk assessment tools that allow a structured risk assessment. The data were grouped to predefined high and low risk groups and aggregate and individual scores. The primary outcome was to validate the predictive value of the RAI score and the TUG for overall survival in the high and low risk groups. Secondary outcomes were surgical outcomes at 90-days after surgery (overall survival, Clavien-Dindo (CD) 1–5 (all complications), and CD 3–5 (major complications)). The study was carried out in accordance with the DIN ISO 14,155, and the medical device regulation (MDR) at Frankfurt University Hospital between March 2022 and January 2023. Results In total 267 patients were included in the intention to treat analysis. The mean age was 62.1 ± 12.4 years. Patients with a RAI score > 25 and/or a timed up and go (TUG) > 8 s had a higher risk for mortality at 90 days after surgery. The low-risk group predicted beneficial outcome and the high-risk group predicted adverse outcome in the ROC analysis (Area Under the Curve Receiver Operator Characteristics: AUROC > 0.800; p = 0.01). Risk groups (high vs. low) showed significant differences for 90-day survival (99.4% vs. 95.5%; p = 0.04) and major complications (16.4% vs. 32.4%; p < 0.001). Conclusion The proof-of-concept trial showed that a risk assessment with ‘The Prehab App’ may be viable to estimate the preoperative risk for mortality and major complications before major surgeries. The overall performance in this initial set of data indicated a certain reliability of the scoring and risk grouping, especially of the RAI score and the TUG. A larger data set will be required to proof the generalizability of the risk scoring to every subgroup and may be fostered by artificial intelligence approaches. Trial registration Ethics number: 2021-483-MDR/MPDG-zuständig monocentric; The Federal Institute for Pharmaceuticals and Medical Devices/BfArM, reference number: 94.1.04-5660-13655; Eudamed: CIV-21-07-0307311; German Clinical Trial Registry: DRKS 00026985.

Abstract Introduction: Surgery puts patients at relevant risk for complications. Knowing a patient's risk helps to identify modifiable and unmodifiable factors to weigh the benefit of surgery against the risk of harm. A structured data analysis with validated tools will increase the reliability of risk assessment. Digitized solutions may add additional value. The Protego Maxima trial evaluated a health app for structured risk assessment before major surgeries and utilizing. The hypothesis was that the structured assessment is predictive of short-term surgical quality. Methods: Patients undergoing major surgery were risk-scored with the software (The Prehab App), and the scores were correlated with 90-day outcomes (survival, Clavien-Dindo (CD) 1-5 (all complications), and CD 3-5 (major complications)). Results: The study included 267 patients. Mean age was 62.1 ± 12.4 years, the risk analysis index (RAI)-score was 21.5 ± 9.7, the timed up and go (TUG) was 7.7 ± 2.3 seconds, 89 patients (33%) were anemic, and 238 patients had an Eastern Cooperative Oncology Group (ECOG) score of 0 (89.1%), 23 of 1 (8.6%), 6 of 2 or 3 (2.3%) which defined the risk groups (low risk: 156 (58.4%), high risk: 111 (41.6%). Receiver operator characteristics (ROC) showed a highly significant potential of the risk score in its prediction of mortality for the high-risk group (Area Under the Curve Receiver Operator Characteristics: AUROC = 0.842) and for the low-risk group (AUROC = 0,990) with difference in AUROCs of -0.149 (95% CI: -0.263; -0.034; p=0.01). The 90-day mortality was 2.2%. Complication rates were 59.9%; major complication rates were 22.5%. Risk groups (high vs. low) showed significant differences for 90-day survival (99.4% vs. 95.5%; p=0.04) and major complications (16.4% vs. 32.4%; p<0.001). Conclusion: The risk assessment with The Prehab App is a viable method to identify risk factors for mortality before major surgeries. The specific validated scoring tools deliver robust and reliable data.

Adhesions are recognised as one of the most common complications of abdominal surgery; their diagnosis and prevention remains a significant unmet need in surgical therapy, affecting negatively a patient’s quality of life and healthcare budgets. In addition, postoperative pelvic adhesions pose a high risk of reduced fertility in women of childbearing age. These 2023 Global Recommendations on Adhesion Prevention in Gynaecological Laparoscopic Surgery provide agreed-upon statements to guide clinical practice, with the ultimate goal of improving patient outcomes.

Background. Before the era of immunotherapies and antibody-drug conjugates, there were limited chemotherapeutic options for patients with recurrent and metastatic cervical cancer. Combination therapies with cisplatin have shown some superiority over monotherapy. This study examined platinum -free treatment regimens, comparing a combination of topotecan and paclitaxel (TP) with topotecan and cisplatin (TC) in patients with recurrent or metastatic cervical cancer, with or without prior platinum -based treatment. Methods. The AGO-Zervix-1 Study (NCT01405235) is a prospective, randomized phase III study in which patients were randomly assigned at a 1:1 ratio to treatment within the control arm with topotecan (0.75 mg/m 2 ) on days 1-3 and cisplatin (50 mg/m 2 ) on day 1 every 3 weeks and in the study arm topotecan (1.75 mg/m 2 ) and paclitaxel (70 mg/m 2 ) on days 1, 8, and 15 every 4 weeks or treatment. The primary study aim was overall survival; progression -free survival, toxicity, and quality of life were secondary aims. The interim and final analysis is here reported after recruitment of 173 of 312 planned patients. Results. Median overall survival in the TP arm was 9.6 months, compared with 12.0 months in the TC arm (log -rank test, P = 0.33). Median progression -free survival rates were 4.4 months with TP and 4.2 months with TC (log -rank test, P = 0.47). Leukopenia and nausea/vomiting were more frequent in the cisplatincontaining arm. Otherwise, toxicity pro files were comparable. There were no differences in FACT-G -assessed quality of life. Conclusion. Platinum -based combination chemotherapy remains the standard of care chemotherapy regimen for patients with recurrent or metastatic cervical cancer. (c) 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

The purpose of the study is to retrospectively evaluate the development and technological progress in local oncological treatments of patients with breast cancer liver metastasis (BCLM) using LITT (laser interstitial thermotherapy), MWA (microwave ablation) and TACE (transarterial chemoembolization) ablation techniques in a multimodal application. The study uses data generated between 1993 and 2020. Therapy results were evaluated using the Kaplan-Meier survival estimate, Cox proportional hazard regression and log-rank test. Cox regression analysis showed that the different treatment methods are statistically significant predictors of survival of patients. Median survival times for groups treated with LITT (212 patients) and LITT + TACE (215 patients) were 2.2 years and 2.1 years respectively; median survival times for groups treated with MWA (17 patients) and MWA + TACE (143 patients) were 5.6 and 2.4 years respectively. For LITT only treatments, the 1-, 3- and 5-year survival probability scored 80%, 37%, 22%. Results for combined LITT + TACE treatments were 76%, 34% and 15%. In group MWA, the 1-/3-/5-year survival probability rates were calculated as 89%, 89%, 89% (however, they should be interpreted carefully due to a relatively small sample size of n = 17 patients). Group MWA + TACE offered values of 77%, 38% and 22%. A separate group of 549 patients was analyzed with TACE monotherapy treatment. The estimated median survival time in this group was 0.8 years. The 1-/3-/5-year survival probability rates were 37%, 8% and 4%. Treatments with combined MWA and MWA + TACE resulted in the best median survival time estimations in this study.

AIM: To evaluate the prognostic value of background parenchymal enhancement (BPE) in breast magnetic resonance imaging (MRI) in women referred to radiological department as a high risk for breast cancer.MATERIALS AND METHODS: A retrospective, cross-sectional study included 327 consecutive patients (mean age: 60 years, age range: 30-90 years) who underwent breast MRI and tissue biopsy between 2007 and 2016. All MRI images (T1, T2, and subtraction images) were evalu-ated visually. The relationship of BPE with patient age, fibroglandular tissue (FGT), Breast Imaging Reporting and Data System (BIRADS) categories, presence of breast cancer, and expression of human epidermal growth factor receptor 2 (HER2), progesterone receptor (PR), oestrogen receptor (ER), and Ki67 were analysed. Furthermore, all variables were correlated with pre-and postmenopausal status.RESULTS: BPE of bilateral breast showed a weak correlation with FGT (right BPE: r=-0.14, p=0.004; left BPE: r=0.16, p=0.0 03), a weak negative correlation with patient age (right BPE: r=-0.14, p=0.0 07; left BPE: r=-0.15, p=0.006), and significant correlation with HER2 (right BPE, p=0.02), left BPE with HER2 was not significant. Among the correlations between BPE and BIRADS, only between right BPE and right BIRADS was significant (p=0.031). No clear evidence of an association between breast MRI BPE and breast cancer in premenopausal and post-menopausal status was observed, and no difference was found between the right and left breasts.CONCLUSIONS: The results of the present study showed no significant correlations between BPE and breast cancer. In addition, there was no significant difference between the right and left breast. Hence, BPE of MRI may not be a reliable biomarker of breast cancer development.& COPY; 2023 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.

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

Introduction/Background The need for contralateral full groin dissection after bilateral sentinelnode biopsy (SNB) with only unilateral detection of a macrometastasis is unclear. Bilateral inguino-femoral lymphadenectomy (if- LAE) is recommended by German guidelines to avoid groin recurrences which are associated with high morbidity. Few unicenter, retrospective analyses have looked at the risk of contralateral non-sentinel (SNL) metastases with conflicting results. Methodology The AGO VOP.2 QS vulva study is a retrospective,multicenter study. Within the study, therapeutic data from n=306 patients, diagnosed with primary groin node positive vulvar squamous cell carcinoma (VSCC) between 2017–2019 at 33 gynecologic cancer centers in Germany were collected. In the current subgroup analysis, only patients with bilateral SNB and unilateral positive SNL were included. Results Of 306 documented groin node positive patients, 137 received bilateral SNB. Of these, 98 had unilateral positive SNL.58/98 (59.18%) received a consecutive bilateral if- LAE. 30/98 (30.61%) underwent unilateral if- LAE and 10/98 (10.2%) had none. Of 98 patients with unilateral positive SNL, two patients (2.04%) showed positive contralateral non-SNL. In the first patient with a midline VSCC a contralateral non-SNL metastasis was detected, despite two negative SNLs in this groin. Bilateral LAE and adjuvant chemoradiation of groins and pelvis were performed and there is no sign of recurrence 18 months after first diagnosis (FD). In the second patient one non-SNL metastasis of 2 mm was detected during LAE after a negative SNL node in the same groin. This patient received radiation to vulva and groins. She suffered from isolated groin recurrence in the groin were the SNL metastasis was initially detected, 11 months after FD. Conclusion In this large multicentre retrospective trial the risk of contralateral non-SNL metastasis is low. Therefore, morbidity should be carefully balanced against oncologic safety and omission of contralateral LAE should be considered, especially in multimorbid or obese patients.

“Historically, most things, most people ever believed to be true eventually turned out not to be true.“ We live in the age of science. At least, that is what we like to believe. With the science-driven industrial revolution starting in the 18th century, and the science-driven revolution of academic medicine starting in the second half of the 19th century, we have become accustomed to knowing more and more about this world in an objective and scientific way. And, curiously, every generation naturally believes, they know everything. Looking back, it is hard to understand, how our forefathers could have believed in bloodletting as the major medical intervention for centuries. It was seen as “the truth“ and people who might have doubted its rationale were marginalised. Today we know it was misguided at best and probably killed innumerably more patients than it saved. Then there was the world before we understood the true role of bacteria. It is curious to read about the treatment of tuberculosis before the invention of antibiotics. In Thomas Mann’s Zauberberg (The Magic Mountain), we encounter a world of scientifically based treatments, that today leave us bewildered. Reading Albert Camus’s “La Peste” leaves us wondering: why don’t they just take the antibiotics and get it over with. What was the best available “scientific” evidence in the past, is often a curiosity today. With this in mind, we should take a critical look at current scientific facts and controversies and we have good reason to do so. Truth, fake news and alternative facts have kept us busy in the world of politics; we all know that. It is a naive thought to believe that the world of science would be immune to these problems. In its review of the most read articles of 2020, JAMA, the Journal of the American Medical Associations, allows some insight into the politics of science and the power of scientific fashions. On January 15th 2020, Rita Rubin published a commentary entitled “Backlash Over Meat Dietary Recommendations Raises Questions About Corporate Ties to Nutrition Scientists“ (Rubin 2020). Ms. Rubin described the reaction from certain quarters to publications questioning the widely accepted dangers of red meat consumption. Apparently, red meat consumption is not as unhealthy as often portrayed or, more precisely, the scientific base for such claims is very small. She wrote “Annals Editor-in-Chief Christine Laine, MD, MPH, saw her inbox flooded with roughly 2000 emails—most bore the same message, apparently generated by a bot—in a half hour. Laine’s inbox had to be shut down, she said. Not only was the volume unprecedented in her decade at the helm of the respected journal, the tone of the emails was particularly caustic.“ These were emails criticising the planned publication. It is important to reflect on what is going on here. This was BEFORE the article was actually published, i.e. an effort to suppress its publication after it had gone through a peer review process with someone from that peer-review process leaking the information to interested (and apparently highly opinionated) circles. Of course, the criticism was not: “ I don’t like the article, because it goes against what I think“, it was attacking the scientific base suggesting “This article is not scientific and thus must not be published“. Reproductive endocrinology colleagues report similar behind-the-scenes interactions prior to the recent metanalysis about hormone replacement therapy (HRT) which put the breast cancer risk of HRT in an interesting perspective (Vinogradova Y et al., 2020). After the WHI-study from 2002 which widely discredited HRT was shown more than 10 years later to have been severely mispresented at the time, the ideological nature of a fight about very small risks has become obvious. Roger Lobo provides an interesting review and commentary in Nature Review Endocrinology in 2017. He particularly comments on how the data was presented by NIH officials without input from the original researchers. (Lobo, 2017). HRT, meat consumption are topics that are being discussed within a legal, economic and ideological context. Science does have a powerful objective aspect; however, it is subject to the same passions and manipulations as all political discourse. Inevitably, these controversies always surround what I call “Issues of small risk“, when small but discernible risks, that are statistically present, are unclear and thus disputed with regard to their clinical relevance. In our field of surgical gynaecology we should be careful to identify our own “ideological” disputes and review the data accordingly. Pretending to “let the science speak for itself“ is a typical phrase used by those who are already misrepresenting it. Science does not speak: scientists do. And scientists are human. They have agendas, biases and skeletons in the closet, too. The role of morcellation is such a topic, heavily influenced by the legal system in the United States. Scientific facts suggesting very small risks were surrounded and masked by an emotive issue and a devastating diagnosis. While the FDA placed the risk of the occult leiomyosarcoma at 1/400, a recent Cochrane review puts it at 1/2000 (Zullo et al 2020). It is always worthwhile to also recall the controversy surrounding silicone breast implants and their alleged effect on autoimmune disease in the 90’s. After 5 Billion US-Dollars had been dispersed in legal fees, the ultimate conclusion, 15 years after the allegation, was that there is no connection. The controversy surrounding minimally invasive surgery and cervical cancer is another subject. Here too, small risks are demonstrated once and then carried around as immutable facts, much like the monstrance during the catholic processions. And beyond our own specialty, the discussions surrounding the current coronavirus pandemic and the ongoing controversies about climate change are battles about who owns the truth. The answer must be: probably no-one does. Science is always a clash of opinions and opinions are held with passion. While science can offer glimpses of objectivity, we must never forget: it is a tool in the hands of passionate women and men who, much as they strife, can never be completely objective. As long as we remember that, science will continue to move ahead. Hesitantly, erringly on a path which, maybe, will lead us to the Truth one day.

After the advent and the subsequent gradual disuse of laser technology in gynaecological surgery, in recent years, thanks to technical improvements, this technology is progressively reaffirming itself in various areas of minimally invasive gynaecological surgery ranging from laparoscopy to robotic surgery and hysteroscopy. This paper, through a SWOT (strengths, weaknesses, opportunities and threats) analysis, shows positives and negatives of this technology with particular attention to present and future applications.

Purpose: Storage mites (SM) are ubiquitously found close to human habitation and are a source of allergic reactions ranging from allergic rhinitis and asthma to anaphylactic reactions. Methods: Data on 3,997 patients with suspected -allergic rhinitis were included. We performed correlation of intradermal testing and specific IgE-test results using Cohen's kappa and univariate logistic regression to evaluate the probability of symptoms and the point of time symptoms were reported. In some patients nasal provocation was performed to prove allergic rhinitis. Results: Patients with storage mite sensitization show a high degree of cross reactivity between different storage mite species. Cross reactivity of storage mite species with house dust mites (HDM) was found in 56 % and is only slightly higher than that of other common allergens such as grasses (45 %) or birch (42 %). A correlation of intradermal testing and specific IgE testing could not be found. The most common symptoms of sensitized subjects were nasal obstruction and hyposmia and symptoms were dependent on presence of chronic sinusitis. Nasal provocation was positive in 16 to 33 % of subjects tested. Conclusions: SM are a common sensitization in the study population and should be included in standard skin prick test arrays. Cross sensitization to house dust mites is limited and nasal symptoms are most frequent. Nasal provocation testing is necessary to secure clinical diagnosis of allergy and further research is needed to evaluate the clinical relevance of the high sensitization rates found for intradermal testing.

Journal of Cell Science was made aware of duplicated α-tubulin control blots in Fig. 3C and 3G of J. Cell Sci. (2014) 127, 4740-4749 (doi:10.1242/jcs.155721).The journal approached the Weizmann Institute of Science and asked them to review the original data supplied by the authors. The Weizmann Institute formed an inquiry committee, whose report stated:“The committee was able to confirm the authenticity of the findings, based on a large body of data (original experiments, repeats done prior to publication and recently repeated experiments). The intensity ratio between the Nir2 bands in Fig. 3G and the corrected tubulin bands provided by the author is similar to what was published in the error-containing Fig. 3G. This implies that the correction has no impact on the original findings. The committee concluded that indeed this was a simple mistake.”As the inquiry committee decided that the conclusions of the paper were not affected by the error, the appropriate course of action – according to COPE guidelines – is to publish a Correction.The correct figure panel is shown below:The authors apologise for any inconvenience caused.

Abstract Background: We have previously shown that expression of the IL8/VEGFA-metagene eliminates the good prognostic effect of TILs in TNBC (PMID 21978456, 28750120). We also showed that the VEGFA metagene predicted response to neoadjuvant bevacizumab in the GeparQuinto trial (Karn 2017 SABCS #851166). The main cellular sources of the transcripts that comprise the VEGFA metagene are unknown since mRNA profiling of bulk biopsies contains signals from different cell types. Methods: Individual genes that comprise the VEGFA metagene were measured in bulk tissue- and single cell-RNA-Seq from breast cancer subtypes and normal cells on different platforms (Affymetrix n=4915, Agilent n=597, Illumina n=2433, RNA-Seq n=1215, Exome Capture RNA-Seq n=226, HTG-Seq n=243, sc-RNA-Seq n=24710). For blinded, orthogonal validation we performed immunohistochemistry. Effect of neoadjuvant chemotherapy with or without bevacizumab was studied by RNA-Seq and IHC on samples from GeparQuinto trial. SWOG S0800 (GSE114403), PROMIX (GSE87455), and GeparSixto trials were used for validation. TCGA was mined for mutations and somatic CNA. RNA-Seq from GeparNuevo was used for correlation with checkpoint inhibitor treatment. Results: We identified a stable core of six genes (VEGFA, ANGPTL4, ADM, NDRG1, DDIT4, CSTB) in different cohorts. Strong expression of this signature was mainly restricted to TNBC subtype and associated with poor prognosis within this subgroup. Single cell RNA-Seq of breast epithelial cells from 4 reduction mammoplasties and 4 TNBC revealed that these genes are coexpressed in individual epithelial cells and not associated with endothelial cells. In line with their presumed functions in cellular stress and hypoxia, immunohistochemistry revealed strong para-necrotic expression in TNBC. Moreover, high gene expression in TNBC was associated with mutations in DNA damage control pathways, somatic copy number alterations, and lower TILs. While chemotherapy led to downregulation, bevacizumab increased expression. In multivariate analysis, high pretreatment values predict pCR to both bevacizumab and chemotherapy (OR 2.40, P=0.006), which may be explained by sensitivity of tumors which are already under cellular stress. On the other hand, expression of the VEGFA metagene seems to create an immunosuppressive environment that counteracts the positive prognostic effect of TILs. In pre-treatment biopsies from the GeparNuevo checkpoint inhibitor trial we found a negative correlation of VEGFA metagene expression with the amount of the recently identified tissue-resident memory T cell subset (CD8TRM, PMID 29942092; P=0.002), while the subsequent increase of CD8TRM during treatment was larger in tumors with high VEGFA (P=0.019). Conclusions: Perinecrotic carcinoma cells under stress from hypoxia and or chromosomal instability are the source of the VEGFA metagene signature. Its predictive value in TNBC suggests estimating and reporting the amount of necrosis in the pathology report may be helpful in predicting response to preoperative chemotherapy, and could be used as stratification factor in clinical trials. The signature indicates an immunosuppressive environment and should be further studied in the context of immune therapies in combinations with anti-angiogenic treatment. Citation Format: Karn T, Denkert C, Sinn BV, Weber K, Nekljudova V, Rody A, Meissner T, Hatzis C, El-Balat A, Becker S, Solbach C, Untch M, Schneeweiss A, von Minckwitz G, Loibl S, Pusztai L, Holtrich U. Single-cell profiling identifies hypoxic carcinoma cells as source of an immunosuppressive VEGFA metagene [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-01.