Impact of COVID-19 on breast cancer screening in the Brazilian Unified Health System (SUS)

Objectives: investigating the impact of the pandemic on breast cancer screening in the Unified Health System, in addition to comparing the data obtained from other countries. Method(s): a quantitative cross-sectional observational study was carried out, with references from the Cancer Information System - SISCAN on the number of mammograms performed from 2014 to 2022 by women in Brazil. Result(s): data regarding mammography in the high-risk population showed a drop of 38, 39% from 2019 to 2020. While in screening mammography, the decline was slightly more significant, at 39.18% in the same period. Regarding diagnostic mammography, the reduction was 33.15%, and in target population mammography, the peak was in 2019 with 2.721.075. On the other hand, the performance of mammography in patients already treated had a smaller decrease of 9.35%. Conclusion(s): there was a significant reduction in the number of mammograms performed in 2019 and 2020, which might lead to a late diagnosis of the disease and a worse prognosis.Copyright © 2023 Faculdade de Medicina de Ribeirao Preto - U.S.P.. All rights reserved.

mRNA expression and delivery efficacy of lipid nanoparticles in the cells breast tumor microenvironment: in vitro and in vivo evaluation

During the COVID-19 pandemics we have all witnessed the clinical importance of mRNA as current vaccines and future therapeutics. mRNA therapies have a potential to revolutionize cancer treatment. Delivery of mRNA requires lipid nanoparticles (LNP) to protect the cargo from degradation. mRNA has a negative charge and depends on positively charged lipids to be encapsulated in LNP. These lipids can be either ionizable at certain pH or constantly cationic. Even though previous studies had evaluated the formulation properties of ionizable and cationic LNP systems, there is the need to understand their specificity in terms of mRNA delivery and protein expression in breast cancer tumor microenvironment. The objective of this work was to assess the kinetics of LNP cellular uptake and mRNA expression inv breast cancer (BC) cells and fibroblasts, the most frequent cell type in the tumor microenvironment cells, while studying the mechanisms involved in differential behaviors of LNP formulated with cationic and ionizable lipids. To achieve this goal mRNA-LNP containing ionizable lipids (LNP-A) and cationic lipids (LNP-B) were designed and formulated using Nanoassemblr Benchtop microfluidics mixer (Precision NanoSystems). mRNA-LNP were characterized for size, zeta potential using dynamic light scattering (DLS) and mRNA encapsulation efficiency using RiboGreen assay. LNP were tagged with rhodamine lipid to investigate the uptake kinetic and a reporter GFP mRNA to evaluate mRNA expression in murine 4T1 and human MCF7, MDA-231, SUM-159 and T47D breast cancer cells and BJ fibroblasts. Live fluorescence microscopy imaging, IncuCyte S3, was used to determine the LNP uptake and GFP mRNA expression. In vitro biocompatibility was assessed with WST-1 assay. Additionally, expression of mRNA delivered from LNP in tumor microenvironment was evaluated in vivo in a syngeneic 4T1 breast cancer model using mRNA luciferase and IVIS imaging. mRNA-LNPs possessed an average diameter of 77 - 107 nm, narrow size distribution, neutral zeta potential and high mRNA encapsulation efficiency (>94%). Our results demonstrated that mRNA expression was higher in breast cancer cells when delivered from LNP-A formulation and in BJ fibroblasts when delivered from LNP-B. LNP-A, the ionizable LNP, was tested in the breast cancer cells to confirm the efficacy of the delivery. The highest transfection efficacy, from high to low, T-47D, MCF7, SUM-159, 4T1 and MDA-231.We have further investigated the cellular uptake mechanisms of LNP using uptake pathway inhibitors for caveolae endocytosis, clathrin endocytosis, and phagocytosis. Our data confirm that there are differences in mechanisms that govern the uptake of mRNA LNP in breast cancer cells and fibroblasts. Clathrin-mediated endocytosis was active in 4T1 breast cancer cells for ionizable and cationic LNP. Interestingly, despite in vitro differences in uptake and mRNA expression, in vivo results show that both formulations efficiently delivered luciferasemRNA in the tumor microenvironment. Histology results demonstrated similar luciferase expression for both LNP in tumors. Additionally, we were able to confirm the prominent presence of fibroblast and similar distribution in the 4T1 subcutaneous model which could explain the similar efficacy of cationic and ionizable LNP. Understanding uptake and mRNA expression of different LNP formulations in the tumor microenvironment can help in achieving the necessary protein expression for breast cancer therapies. Furthermore, determining the most efficient carrier in early stages may reduce the time required for clinical translation. Acknowledgement: This research was supported in part by CPRIT Core for RNA Therapeutics and Research.

Impact of the COVID-19 pandemic on the diagnostic pathway of breast cancer in the Netherlands: a population-based study

Objective: The COVID-19 pandemic has had an impact on health care. In the Netherlands, hospital capacity for non-covid care was limited and population screening temporarily halted. The aim of this study was to investigate the impact of the pandemic on the diagnostic pathway of breast cancer. Method(s): In this study, 48,425 breast cancer patients with a primary breast tumour were selected from the Netherlands Cancer Registry and the Dutch Hospital Data. Patients diagnosed in period January 2020 to July 2021 were divided into six periods, based on the number of hospitalizations due to the COVID-19 pandemic and compared to the same periods in 2017-2019. A t-test was performed to compare the number of diagnosed patients per period. Patient characteristics were compared using chi-squared test. The impact on the procedures performed was analysed using logistic regression. The median time between diagnosis and therapy and the median time between first diagnostic procedure and therapy was analysed using Cox Proportional Hazards Regression. All results were corrected for age, stage and region. Result(s): During the first peak of the pandemic in 2020, significantly fewer patients (-48,2%) have been diagnosed with breast cancer. This decrease is mainly seen in lower stage tumours. Mammography and echography were performed significantly less per patient during the first recovery in 2020 (OR=0.83 and OR=0.85 respectively) compared to 2017-2019. PET-CT was performed significantly more often during the first peak and first recovery in 2020 (OR=1.94 and OR=1.39 respectively). The median time between diagnosis and start of therapy significantly decreased in 2020, during the first peak by 3 days (HR=1.26), during first recovery and second peak by 1 day (HR=1.04 and HR=1.16 respectively). The median time between first diagnostic procedure and start of therapy significantly decreased in 2020, during the first peak by 4 days (HR=1.25), during the first recovery by 1 day (HR=1.04) and during the second peak by 2 days (HR=1.13). Conclusion(s): The decreased number of diagnosis was related to the temporary halt of the screening. Diagnostics for early stage tumours was limited and for PET-CT was performed more often reflecting the change in proportion of higher stage. A reduced time of the diagnostic pathway is the result of less hospitalized patients with cancer and the effort on keeping the oncology care in place. (Table Presented).

Comparing operative techniques for non-palpable breast tumours: Wire-guided localisation vs LOCaliser

Introduction: Wire-guided localisation (WGL) has been the standard operative technique for non-palpable breast tumours. LOCaliser is an alternative method, with a clinical effectiveness that may be equal to the standard while providing additional benefits regarding the patient experience. Method(s): A single-centre, retrospective study of WGL vs LOCaliser from January 2020 to December 2021. We collected demographic and outcome data from electronic records. The primary outcome was rates of complications, this included seromas, haematomas, pain and re-excisions. Secondary outcomes included operative time. Result(s): 21 WGL and 16 LOCaliser patients were identified. The average age was similar between the two groups (62 vs 61;P=0.291). There were fewer complications in the LOCaliser group, however without statistical significance (1 vs 5;P=0.206). The LOCaliser group had less re-excisions (1 vs 5;P=0.206), with 3 of 5 patients requiring 2 margins to be re-excised in the WGL group. There was no difference in the operative time between the two groups (107 minutes vs 104 minutes;P=0.070), sub-group analysis was not done to compare axillary node clearances and sentinel lymph node biopsies. Conclusion(s): LOCaliser is as effective if not superior to WGL when measuring clinical outcomes. The data did not demonstrate statistical significance, however demonstrated differences which could become significant with larger patient cohorts. LOCaliser prevented the need for pre-operative procedures, which was particularly important during the COVID-19 pandemic as it reduced patient exposure and hospital attendances prior to surgery. A larger scale audit and assessing patients' experiences by collection patient reported outcomes measures (PROM) would be beneficial. Copyright © 2022

Systematic Review of Biologic Correlates of Frailty in Solid Tumors: Implications for Brain Tumors

BACKGROUND: Cancer and cancer treatments contribute to accelerated aging and frailty, which is present in over 50% of adult cancer survivors and increases vulnerability to poor outcomes. Biomarkers of frailty would allow for early identification and timely interventions. The purpose of this review is to synthesize the current literature examining biomarkers of frailty across solid tumor patients, including primary brain tumors (PBT). METHOD(S): The systematic review was conducted using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. PubMed, Web of Science, and Embase, were searched by the medical librarian (D.C.) of all reports from the inception to December 08, 2021. Inclusion criteria were: a) English language, b) biomarkers of aging hallmarks, c) association between biomarkers and frailty. Studies were limited to human solid tumors. Two reviewers (D.S. and B.P.S.) independently screened titles, s, and full-text articles using Covidence platform with conflict resolution by the third researcher (T.S.A.). Included studies were independently evaluated for quality assessment using NIH tools for Observational Cohort, Cross-Sectional and Case-Control studies. RESULT(S): In total, 915 reports were screened and 15 full-text articles were included for the review. Studies were most commonly in breast tumors with no PBTs identified. Most were cross-sectional using small sample sizes. Fried, Balducci, and Leuven Oncogeriatric Frailty tools and cytokines (i.e. Interleukin-6 and C-reactive protein) were commonly used. Increased inflammatory response was the prevalent identified mechanism. Threats to internal validity of the studies were the use of unvalidated cut-off scores or modification of existing tools in about 50% of studies. Only six studies were rated as good using quality assessment ratings. CONCLUSION(S): Varied use of frailty measures and nonspecific blood biomarkers limited conclusions for mechanisms of frailty in cancer survivors. There are missed opportunities in neuro-oncology;inclusion of frailty assessment and biomarkers is instrumental to advancing science in PBTs.

Accelerated Partial Breast Irradiation (APBI) Using Five Daily Fractions: A Prospective, Phase II, Multi-Centre Trial of Cosmetic Outcomes and Toxicity (The Accel Trial): Final Results

Purpose: To report final results of a clinical trial of APBI using intensity modulated radiotherapy (IMRT) to deliver 27 Gy in 5 daily fractions following breast conserving surgery (BCS) prospectively designed to assess the efficacy and cosmetic outcomes of a oneweek, APBI regimen among women with early breast cancer. Material(s) and Method(s): Women >= 50 years, with lymph nodenegative, ER positive, HER-2 negative breast cancer or ductal carcinoma in situ (DCIS), <= 3cm diameter, following BCS with margins >= 2mm, and excellent or good baseline cosmesis received 27 Gy in 5 daily fractions to the seroma plus 1 cm CTV and 0.7 cm PTV margins. Clinical photographs, patient and provider cosmetic scores, breast fibrosis, telangiectasia and pain were collected prospectively, prior to RT and at 6 weeks, 1 and 2 years after RT. The primary endpoint was the proportion of women who retained Excellent or Good cosmesis at 2 years using the EORTC Cosmetic Rating System. Cosmetic failure was deterioration from Excellent or Good to Fair or Poor. A panel of 5 radiation oncologists independently assessed the cosmetic photographs. Secondary endpoints were rates and grades of breast fibrosis, telangiectasia, breast pain, ipsilateral breast tumour recurrence (IBRT), overall (OS), breast cancer-specific survival (BCSS) and subsequent mastectomy. Efficacy outcomes were assessed at clinic visits and by review of charts. ClinicalTrials.gov registration: NCT02681107. Result(s): A total of 298 patients were treated between April 25, 2016, and October 31, 2019. At a median follow-up of 48 months, the four-year OS was 98.5% (95% CI 96.1% - 99.5%) and BCSS was 99.7% (95% CI 97.6% - 99.9%). The four-year IBRT rate was 3.3% (95% CI 1.1% - 6.4%). There were 10 contralateral breast events for a four-year rate of 3.9% (95% CI 2.2% - 6.9%). There were 10 ipsilateral and six contralateral mastectomies. Two patients died of unrelated causes prior to two years;79 patients declined inclinic attendance due to COVID or competing comorbidities and 217 women had two-year cosmetic photographs and clinical assessments performed. Consensus of the photo-panel cosmesis at baseline was: Excellent: n=116 (53%), Good: n=102 (47%), Fair: n=1 (0.5%) and Poor: n=0. Consensus overall cosmesis at two years was: Excellent: n= 141 (65%), Good: n=78 (35%), Fair: n=0 and Poor: n=0. Most patients had either improved (n=168;77%) or no change (n=43;20%) in cosmesis at two years. No patient had cosmetic failure but 6 (3%) had a change from Excellent to Good at two years. Most patients reported either no (79%) or mild (21%) pain, with no moderate or severe pain. Two patients (0.9%) had Grade 2 fibrosis and five patients (2%) had visible telangiectasia that did not detract from overall cosmesis. Conclusion(s): APBI using 27 Gy in 5 fractions using a conformal IMRT technique, achieved excellent two-year cosmesis with minimal toxicity. The IBRT risk was comparable to the contralateral new breast cancer risk and to local recurrence rates of recently published early breast cancer trials. Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Oncologic Outcome, Toxicity and Cosmesis After Single-Fraction Neoadjuvant Radiotherapy for Low-Risk Breast Cancer

Purpose: Breast-conserving surgery followed by several weeks of adjuvant radiotherapy is the current standard of care for low-risk breast cancer. A novel approach using single-fraction neoadjuvant radiotherapy is under study. We sought to investigate the rate of pathologic response, toxicities and cosmetic results related to this new treatment strategy. Material(s) and Method(s): Women 65 years of age or older with a new diagnosis of Stage I unifocal luminal A breast cancer were eligible for inclusion in this Phase I prospective trial. A single 20 Gy dose of radiotherapy to the breast tumour was given, followed by breast-conserving surgery three months later. The primary endpoint was the pathologic response rate assessed by microscopic evaluation using the Miller-Payne system. The secondary endpoints were the incidence of radiation toxicity and the cosmetic results, graded according to the Common Terminology Criteria for Adverse Events and the European Organisation for Research and Treatment of Cancer Cosmetic Rating System, respectively. Secondary outcomes were assessed at 6 weeks, 4 months and yearly after radiotherapy. Result(s): To date, 13 patients have been successfully treated with a median age of 71 years (range: 65-83 years). As previously reported, neoadjuvant radiotherapy resulted in a tumour pathologic response in 11 of 13 patients with a median residual cellularity of 1% (range: 0-10%). With an average follow-up of 31.9 months (range: 24.4- 39.2 months), no disease recurrences or deaths were recorded. Acute radiation toxicities were limited to Grade 1 dermatitis and breast pain. At the one-year follow-up, 11 patients had Grade 1 toxicities (dermatitis, fibrosis, breast pain and chest wall pain), one patient had a Grade 2 fatty necrosis, and two patients had Grade 3 toxicities (wound infection and hematoma). Only Grade 1 toxicities remained at the two-year follow-up. One-year cosmetic results were good or excellent in 46% of patients according to their self-assessment and in 54% of them according to the nurse's evaluation. Two-year cosmetic results were unavailable due to in-person visits cancellations during the COVID-19 pandemic. Conclusion(s): This study demonstrates that a single fraction of neoadjuvant radiotherapy preceding breast-conserving surgery is feasible, relatively well tolerated and leads to a high level of pathologic response for most patients. The Grade 3 toxicities and underwhelming cosmetic results may indicate that the 3-month interval after radiotherapy places surgery in a post-radiation inflammatory phase. Larger trials are needed to better assess the long-term toxicities as well as the optimal timing and fractionation of this novel technique in the management of early-stage breast cancer. Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Safety of Sputnik V COVID-19 vaccine in cancer patients receiving chemotherapy: An observational study

Background: COVID-2019 had a dramatic impact on cancer care worldwide. There are numerous of vaccines developed or being developed in order to prevent the spread of the disease. A recombinant adenovirus-based vaccine, Gam-COVID-Vac (Sputnik V), has shown a favorable safety profile and efficacy in Phase 3 trial. Nowadays it is a main SARS-CoV-2 vaccine in Russia, but there is lack of information on its safety in cancer patients. We conducted a retrospective trial to assess safety of Sputnik V in adult patients with cancer. Method(s): we screened N.N. Blokhin NMRCO records for 01.2021-05.2022 timeframe and identified adult cancer patients vaccinated against SARS-CoV-2 with Sputnik V vaccine and contacted them to assess the tolerability and safety of the above mentioned vaccine. The patients were asked to report any new adverse events they experienced up to 28 days after the last dose of the vaccine. All the adverse events were recorded in the database and graded according to CTCAE criteria. Patients were specifically asked to report the following: pyrexia, asthenia, nausea, vomiting, local reactions, abdominal pain, muscle or joint pain and to report any other concerning symptoms. Symptoms were graded according to CTCAE4.03 criteria. Result(s): we identified 145 patients who received at least 1 dose of vaccine, safety data were available for 141 of them. Median age was 55 years (21-83), 70 (48.9%), 27 (19.2%), 21 (14.9%) and 19 (13.5%) patients had gynecologic, breast, genitourinary, gastrointestinal tumors, respectively;5 (3.5%) of patients had other types of tumors. Overall, 70 (49.6%) of patients experienced AE of any grade. Most common AEs were injection reactions (40.4%), pyrexia (24.1%), asthenia (22.0%) and arthralgia (13.5%), results are summarized in the table below. Few patients experienced grade 3-4 AEs, however 1 patient developed grade 4 cerebellar ataxia probably related to vaccination. Cancer type and active treatment were not predictors of AEs. [Formula presented]. Conclusion(s): Sputnik V vaccination appears to be safe and tolerable in patients with cancer, however additional studies should be conducted to assess efficacy and safety of the vaccine in cancer setting. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: A. Rumyantsev: Financial Interests, Personal, Invited Speaker: BIOCAD, AstraZeneca, Eisai, Pfizer, Merck, MSD, R-Pharm;Financial Interests, Personal, Stocks/Shares: AstraZeneca, Pfizer, Novartis, MSD. E. Glazkova: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, MSD, Merck, Novartis, R-Pharm. A. Tryakin: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Eli Lilly, Merck, Amgen, Biocad;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Astra Zeneca, Biocad;Financial Interests, Personal, Expert Testimony: R-pharm;Financial Interests, Institutional, Invited Speaker: MSD, BMS;Financial Interests, Personal and Institutional, Invited Speaker: Eli Lilly. A. Tyulyandina: Financial Interests, Personal, Funding: AstraZeneca, Roche, MSD, RUSSCO;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Eisai;Financial Interests, Personal, Invited Speaker: Roche, MSD, Pfizer, Tesaro, BIOCAD. All other authors have declared no conflicts of interest. Copyright © 2022

The impact of face-to-face evaluation in the clinical assessment of cancer patients

Background: Despite the growing popularity of teleoncology in the context of the COVID-19 pandemic, there is great concern about the quality and accuracy of clinical encounters as there is virtually no physical examination (PE) provided. Objectives: To evaluate the primary sites and clinical variables that could predict a higher frequency of abnormal PE findings and a consequent change in conduct, thus allowing the selection of patients who are possibly ineligible for remote care. Methods: Observational and prospective study, conducted at the oncology center of two public hospitals in Brazil. A multiple- choice form, developed by the researchers, was filled in to collect the clinical variables of the patients, data regarding the service, and oncological conduct determined at the end of the consultation. Results: 368 clinical evaluations of patients with cancer were included in the study, with breast, colorectal, and prostate tumors being the most frequent. The physical examination was normal or with alterations already seen in previous consultations in 87% of the cases while 13% had new changes in the PE. Among patients with new changes in the PE, cancer treatment was maintained in 59% of cases. Thus, PE led to a change in antineoplastic therapy in 12 cases (3% of all patients being 1% only because of the PE findings and 2% after completion of a complimentary examination). Statistical analysis showed a significant association between the altered PE and the following variables: primary site breast (n=27;21%;p<0.01), head and neck (n=7;26%;p<0, 01) and ovary (n=2;17%;p<0.01), presence of symptoms (n=31;21%;p<0.01), and treatment with palliative intent (n=23;19%;p<0.01). However, only the presence of symptoms showed a positive association with the altered PE and consequent treatment change (p<0.01). Conclusions: Telemedicine seems to be a safe modality in the vast majority of cases, given the large percentage of asymptomatic patients with no changes in the PE during face-to-face care. Regarding symptomatic patients, we suggest priority to in-person care. In those with EC IV tumors undergoing palliative treatment or with breast, head and neck, and ovarian cancer, we recommend evaluating case by case and considering face-to-face care.

Inhibition of estrogen receptor signaling as a strategy for radiosensitization of ER+ breast cancers

Purpose: The estrogen receptor (ER) is expressed in over 80% of breast tumors and has been shown to be a significant driver of breast cancer (BC) pathogenesis and therefore a target of effective first-line therapies. While both ionizing radiation (RT) and endocrine therapies (ET) are used for the treatment of ER+ BC, the effect of ET on tumor radiosensitization remains unclear, with concerns it may be radioprotective based on G1 cell arrest with ET treatment. Here we assessed the efficacy and mechanism of ER-mediated radiosensitization using various pharmacologic approaches in ER+ BC. Methods: Radiosensitization with ER inhibitors (tamoxifen [TAM], fulvestrant [FULV], AZD9496) was assessed using clonogenic survival assays. DNA damage was assessed by the neutral comet assay. Efficiency of homologous recombination (HR) or non-homologous end joining (NHEJ) as well as changes in cell cycle, apoptosis, and senescence were assessed. The efficacy of TAM with RT in vivo was assessed with an MCF-7 xenograft model. Results: The selective estrogen receptor modulator TAM radiosensitized ER+ MCF-7 (enhancement ratio [enhR]: 1.14-1.50) and T47D (enhR: 1.33-1.60) cells but not ER-negative SUM-159 cells (enhR: 0.99-1.02). The selective estrogen receptor degrader (SERD) FULV had similar radiosensitization effects in MCF-7 (enhR: 1.33-1.76) and T47D cells (enhR: 0.97-2.81) with no radiosensitization observed in SUM-159 cells (enhR: 1.01-1.03). The novel oral SERD AZD9496 radiosensitized MCF-7 cells (enhR: 1.36-1.56). MCF-7 cells treated with TAM and RT had an increase in dsDNA breaks compared to RT alone as measured by the comet assay (p<0.05) and a decrease in NHEJ-mediated repair with TAM (p<0.05). No changes were observed in HR-mediated repair by Rad51 foci or a reporter (p=NS). RT alone and in combination with TAM or FULV induced similar levels of cell cycle arrest, suggesting that radiosensitization with the combination therapy is cell-cycle independent. There were no significant changes in apoptosis with TAM, FULV, RT, or the combination (p=NS). Although TAM or FULV did induce senescence, ET with RT increased senescence induction (p<0.05). In vivo, combination RT and TAM led to a significant delay in days to tumor doubling (control: 17, TAM: 40, RT: 32, TAM+RT: undefined;p<0.0001), and a significant difference in tumor growth between mice treated with TAM or RT alone compared combination treatment, with no increased toxicities or skin lesions from the combination treatment. Conclusion: Our data suggest that TAM, FULV, or AZD9496 can radiosensitize ER+ breast tumors, and these agents with RT may be more effective for radiosensitization. This work also supports further clinical investigation of the timing of RT for patients receiving ET, including using ET during RT, especially as initiating ET prior to RT has been increasingly utilized as a bridging therapy followed by concurrent ET+RT during the COVID-19 pandemic.

Social isolation promotes mammary cancer recurrence, increases IL6/JAK/STAT3 signaling and causes mitochondrial dysfunction in tamoxifen treated rats, and a traditional herbal mixture reverses all these changes

Social isolation is associated with increased risk and mortality from many diseases, such as breast cancer. Socially isolated breast cancer survivors have a 43% higher risk of recurrence and a 64% higher risk of breast cancer-specific mortality than socially integrated survivors. Since Covid-19 has dramatically increased the incidence of social isolation, it is important to determine if social isolation affects the response to endocrine therapy and/or recurrence after the therapy is completed. Since previous studies indicate that social isolation increases circulating inflammatory cytokines, we investigated if an anti-inflammatory herbal mixture Jaeumkanghwa-tang (JGT) prevents the adverse effects of social isolation on breast cancer mortality. Estrogen receptor positive mammary tumors were initiated with 7,12-dimethylbenz[a]anthracene. When a rat developed a palpable mammary tumor, it was either socially isolated (SI) by housing it singly or a rat was allowed to remain group-housed (GH). Tamoxifen (340ppm via diet) or tamoxifen + JGT (500ppm via drinking water) started when the first mammary tumor reached a size of 11 mm in diameter. Tamoxifen administration ended when a complete response to this therapy had lasted for 9 weeks (corresponds to 5 years in women). During tamoxifen therapy, social isolation non-significantly reduced the rate of complete responses to 21%, from 31% in GH group (p>0.05). After the therapy was completed, SI significantly increased local mammary tumor recurrence (p<0.001;45% GH vs 75% SI). RNAseq analysis was performed in the mammary glands. Gene set enrichment analysis (GSEA) of transcriptome showed that the increased recurrence risk in socially isolated rats was associated with an enrichment of IL6/JAK/STAT3 signaling: this result was confirmed in the tumors. In addition, oxidative phosphorylation (OXPHOS) pathway was suppressed: the suppressed genes included those involved in mitochondrial pyruvate transport and conversion of pyruvate to acetyl CoA as well as genes in the TCA cycle and mediating electron transport in mitochondrial complexes I-IV. Social isolation also increased the expression of inflammatory receptor for advanced glycation end-products (RAGE) (p≤0.05). Consumption of an anti-inflammatory JGT inhibited IL6/JAK/STAT3 signaling, upregulated OXPHOS signaling and prevented the increased risk of mammary cancer recurrence in socially isolated animals. The percentage of recurrences in the SI rats dropped from 75% without JGT to 22% with JGT (p<0.001). Breast cancer mortality among socially isolated survivors may be most effectively prevented by focusing on the period following endocrine therapy using tools that inhibit IL6/JAK/STAT3 inflammatory cytokine signaling and correct disrupted OXPHOS and mitochondrial dysfunction.

The impact of breast care nurse triage of referrals to one-stop clinic on detection of breast cancer

Introduction: To minimise footfall during COVID pandemic, breast care nurse (BCN) led triage of the referral letters was used in our department. Based on the referral history, the nurse would triage patients to be seen in the one-stop clinic, consultant telephone consultation or telephone BCN-led pain clinic. The study aimed to assess the effect of BCN-led triage on detection of cancer and number of patients seen in the clinic. Methods: A retrospective observational analysis was conducted for all referrals to one-stop clinic at breast unit in Broomfield Hospital from 1st-30th July 2020. Results: Of the total number of patients (n=225) triaged by the BCN, majority were females (M:F 2:223) having a mean age of 55.1 years (14-90). Most patients presented with a breast lump (152/225). 12% (n=27/225) of the patients were diagnosed with cancer. The average number of cancers identified per week were 4.4 (3-6) with the BCN identifying 67.5% (n=27/40) of them. The mean time to referral to initial decision was 2.6 days (0-14) with BCN-led triage compared to routine referral route (10.7 days [1-23]). 27 patients (12%) were triaged to telephone breast pain clinic. 1 patient re-attended the clinic after being discharged from pain clinic with persistent pain but not diagnosed with cancer. Conclusion: BCN-led triage had a higher rate of breast cancer detection and less time taken from referral to decision for breast patients. The BCN-led pain clinic reduced the number of patients seen in the one-stop clinic without missing any cancer diagnosis.

The effect of virtual consultant-led consultation of breast patient with new symptoms on service delivery during COVID pandemic

Introduction: During the COVID pandemic, all referrals to the breast unit were telephone triaged by the consultant surgeons prior to offering a clinical appointment at the one stop clinic to minimise footfall into the hospital and reduce social contact. The study aimed to assess the impact of telephone led consultations on the service delivery of one-stop clinic. Methods: A retrospective observational analysis of all referrals to the breast unit from 1st June 2020 to end of July 2020 at the Breast Unit, Broomfield Hospital, Chelmsford. All referrals to the breast unit from the community and other specialties were analysed. Results: A total of 399 patients were called by the consultants. 35.8% of the patients (M:F 25:118) were discharged following telephone consultation. The commonest presentation of the telephoned discharged patients was breast lump. The re-attendance rate following telephone discharge was 20.3% and the mean re-attender age was 34.9 years (17-65). The commonest presentation was lump and pain. None of the re-attenders were diagnosed with cancer and were discharged after clinic review. Following an initial telephone consult, patients were stratified by risk and 37 patients were deferred for a longer period of approximately 3 months to either a further telephone consult or a delayed one-stop. There was no re-attendance of these patients during the study period. There were 2 female cancers identified in the deferred patients. Conclusion: Consultant led telephone triage of one-stop clinic is safe and reduces number of patients seen in the clinic, however, the re-attendance rate is high.

Physical and visual (social) isolation increases tumor aggressiveness in thermoneutral housin temperatures in murine mammary cancer models

Correct interpretation of tumor progression data, including the influence of host biology, in mouse models of breast cancer requires models and conditions that faithfully recapitulate human disease and human host status. Our previous attempts to investigate the effects of social isolation have proven inconclusive due to premature mortality in tumor-bearing animals. Those studies were completed in standard temperature (ST), which commonly is 70-72°F (21-22°C) for in vivo murine research based on laboratory animal care and use guidelines. Previous work from the Repasky lab (Kokulus, 2013), which we have validated (Gaymon, 2020), demonstrates that ST housing results in chronic cold stress and immune suppression mediated by an increase in norepinrephrine (NE) levels, leading to increased tumor aggressiveness. Based on these findings, we investigated the effects of social isolation on BALB/cJ-4T1-luc and C57BL/6J/E0771 tumor progression and metastasis in thermoneutral housing conditions (84-85°F). Mice were first acclimatized to thermoneutral temperature and/or isolation for two weeks in cages that were unilaterally draped to provide physical and visual isolation. In BALB/cJ mice, 4T1-luc tumors were significantly larger in isolated mice compared to group-housed (GH) mice at day 18 (p<.0001). Statistically larger tumors were observed in isolated mice compared to GH mice through day 24 and final tumor masses were Salso significantly different (p=.004). Spleen masses were not statistically different. In C57BL/6J mice, E0771 tumors were significantly larger in isolates at Day 25 (p=.002). Final tumor masses were statistically (p=.002) different while no difference in spleen sizes were observed. Data on metastasis will be presented at the meeting. We hypothesized that social isolation may perturb immune function and next investigated the growth of 4T1-luc xenograft tumors in NSG mice. 4T1-luc/NSG tumor progression and metastasis data will also be presented at the meeting. We conclude that syngeneic breast tumor growth in immunocompetent BALB/cJ and C57BL/6J mice demonstrates that social isolation is a bona fide stress with sufficient influence to exacerbate breast cancer growth. These data are potentially clinically important due the known relationship of social support to survivorship outcomes in patients and the high-risk of depression and isolation in patients following breast cancer diagnosis. The data may provide additional insight into possible effects of COVID-19 isolation on breast cancer progression.

Endocrine therapy treatment radiosensitizes estrogen receptor-positive breast cancers

Purpose: Estrogen receptor (ER) expression is present in over 80% of breast tumors and has been shown to be a significant driver of breast cancer (BC) pathogenesis and therefore a target of first-line therapies for ER-positive (ER+) BC patients. While both ionizing radiation (RT) and endocrine therapies (ET) are used for the treatment of ER+ BC, the sequencing of therapy and the effect of ET on tumor radiosensitization remain unclear. Recently, this question has become much more clinically relevant when many physicians started offering ET as a bridging strategy to surgery and RT during the COVID-19 pandemic. Here we assessed the efficacy and mechanism of ER inhibition in ER+ BC in combination with RT in preclinical models. Methods: Clonogenic survival assays were used to assess radiosensitization. Inhibition of ER signaling was accomplished by treating ER+ MCF-7 and T47D cells with the selective ER modulator (SERM), tamoxifen, or the selective ER degrader (SERD), fulvestrant. The ER-negative SUM-159 cells were used as a negative control. DNA damage was assessed by the neutral comet assay. Efficiency of homologous recombination (HR) was measured by Rad51 foci or a GFP reporter system. Non-homologous end joining (NHEJ) efficiency was assessed with a pEYFP reporter. Cell cycle effects were measured using flow cytometry with propidium iodide (PI) staining. Apoptosis was assessed by annexin V/PI via flow Scytometry. Senescence was measured using β-galactosidase staining. Western blotting was used to quantify expression of proteins and phospho-proteins involved in cell cycle and apoptosis. An MCF-7 xenograft model was used to assess the efficacy of tamoxifen with RT in vivo. Synergy was determined using the fractional tumor volume (FTV) method. Results: ER inhibition with tamoxifen radiosensitized ER+ MCF-7 (10-250 nM, enhR: 1.14-1.50) and T47D (500 nM-2.0 μ M, enhR: 1.33-1.60) cells but not ER-negative SUM-159 cells (500 nM-2.0 μ M, enhR: 0.99-1.02). ER degradation with fulvestrant had similar radiosensitization effects in MCF-7 (1-25 nM, enhR: 1.33-1.76) and T47D cells (0.5-5 nM, enhR: 0.97-2.81) with no radiosensitization observed in SUM-159 cells (1-25 nM, enhR: 1.01-1.03). MCF-7 cells treated with 500 nM tamoxifen and 4 Gy RT had an increase in dsDNA breaks compared to RT alone as measured by the comet assay (p<0.05), and there was a decrease in NHEJ-mediated repair with tamoxifen treatment (p<0.05). No changes were observed in HR-mediated repair by Rad51 foci or an HR reporter (p=NS). RT alone and in combination with tamoxifen and fulvestrant induced similar levels of cell cycle arrest, suggesting that radiosensitization with the combination therapy is a cell-cycle independent effect. In addition, there were no significant changes in apoptosis in MCF-7 or T47D cells with endocrine therapy, RT, or the combination (p=NS). Although treatment with ET did induce senescence in ER+ MCF-7 and T47D cells, the combination treatment of ET with RT induced senescence to a much greater level suggesting this mechanism may contribute to radiosensitization (p<0.05). In vivo, combination RT and tamoxifen led to a significant delay in time to tumor doubling (17 days in control, 40 days with tamoxifen alone, 32 days with RT alone, and undefined with combination;p<0.0001) and a significant difference in tumor growth between mice treated with tamoxifen or RT alone compared to mice treated with tamoxifen and RT with synergy noted with combination treatment (FTV 1.297). Conclusion: Our data suggest that ET can radiosensitize ER+ breast tumors, and ET with RT may be more effective for radiosensitization. Ongoing studies will address concurrent versus sequential ET with RT. This work also supports further clinical investigation of the timing of RT for patients receiving ET, especially as ET prior to RT is increasingly used as a bridging therapy during the COVID-19 pandemic.

Telephone triaging during the 1st wave of the COVID 19 Pandemic: Outcomes and proposed pathway for managing patients referred for breast pain

Introduction/Background• The sudden outbreak of the COVID 19 pandemic led to increased stress on healthcare systems across the globe. They struggled to continue to provide other essential clinical services whilst dealing with the rapid surge of COVID 19 cases. It was therefore essential to optimize patient-centred care safely in a risk adapted environment without compromising outcomes.• We present our experience of telephone triaging of new symptomatic patients referred to a single, tertiary, academic large volume breast unit. Based on our observed outcomes, we propose a novel pathway for management of patients referred with Breast Pain. Methodology• We conducted an audit of patients triaged for telephone consultation at Guy's and St Thomas' NHS foundation Trust, UK between 1st April 2020 to 30th June 2020. Data was collected retrospectively from hospital records following approval from the Trust Audit Committee. Two week wait (2WW) referrals determined to be of low index of suspicion for breast cancer were triaged to telephone consultation. Criteria for low index of suspicion was breast pain, non-suspicious skin changes, bilateral non pathological nipple discharge, gynaecomastia, patients < 30. Patients > 70 were initially offered telephone consultation for risk assessment to avoid potential exposure to COVID19 (shielding of vulnerable cohort). Follow up data was recorded up to October 2020. SResults• There were a total of 685 new 2WW referrals during this time. The total number of patients that were triaged to telephone consultation were 111. The median age of this cohort was 34. There were 105 women and 6 men in this cohort. When classified by symptoms, 47 were referred for breast pain, 46 for suspected breast lumps, 6 for nipple discharge and 12 for other miscellaneous reasons.• The total number of patients that were invited back for imaging or face to face (F2F) consultation or both were 67 (60%).Total number that came back for F2F consultation were 50, out of which 14 were purely for F2F. The total number of patients that came back for imaging were 53, out of which 17 came for imaging only. Total number that came back for F2F and imaging both were 36.• 44 patients were discharged without a F2F consultation or imaging (40%)• F2F consultations (50) when classified by symptoms, 70% presented with breast lump, 14% with breast pain, 6% with nipple discharge, 2% with breast infections and 8% with other benign causes.• Total number of biopsies performed were 9, out of which 2 were cancers and the rest were benign.• There were 3 patients that came back with new referrals after a few months of being discharged following a telephone consultation. They presented with the same symptoms, or their symptoms had worsened or they had new symptoms. However, none of them had any significant finding on F2F consultations or imaging and were reassured and discharged. Conclusion• Our audit (although a small cohort), some published data (Cancer Waiting Times data in the UK comparing 1st 6 months from 2019 with 2020) and literature support the effectiveness of this tool in unprecedented times.• Breast pain is not the most alarming symptom. None of the patients in our cohort with breast pain were found to have any significant finding on imaging or were diagnosed with breast cancer.• Any breast lump or pathological nipple discharge irrespective of age should undergo triple assessment as gold standard.• Our proposal is to design a separate pathway for patients with breast pain as they do not necessarily need a F2F consultation or imaging (can be elicited by the clinician and called only if deemed necessary). This will in turn decrease the strain of 2WW referrals and increased burden on radiology.

Effect of the COVID outbreak on detection of second primary breast cancer and breast cancer recurrences

Introduction: The COVID-19 pandemic led to a decrease in the incidence of breast cancer diagnoses in the Netherlands. This was due to the encouragement to stay at home, a lack of capacity at the general practitioner (GP) and an increased reluctance of patients to visit the GP. Moreover, from the 16th of March the Dutch breast cancer screening program was halted and gradually restarted from June onwards. Part of the follow-up visits for breast cancer survivors were also postponed or changed to an appointment by phone. However, it is not known how this affected the incidence of second primary breast cancer (SPBC) and pathologically confirmed breast cancer recurrences. Objective: To investigate the effect of the COVID-19 pandemic on the diagnosis of SPBC and breast cancer recurrences. Methods: Women diagnosed with a pathological confirmed SPBC or recurrence (locoregional recurrences (LRR) + distant metastasis (DM)) between January 1st 2017 and February 28th 2021 were selected from the Netherlands Cancer Registry, based on diagnoses of the Nationwide Histopathology and Cytopathology Data Network and Archive (PALGA). Patients with a SPBC or recurrence who had their primary breast tumor diagnosed more than five years ago were excluded. March 1st 2020 till February 28th 2021 was regarded as the S COVID-19 period. Incidence was expressed per 100, 000 women, who were diagnosed with breast cancer less than 5 years ago, and who were still alive. Incidence of SPBCs and recurrences was calculated for the total COVID-19 period and for four subperiods, and compared with the corresponding periods in 2017/2019 (averaged). Results: A total of 393 patients were diagnosed with a SPBCs in 2017, 340 in 2018, 299 in 2019, 342 in 2020 and 71 up to February 2021. A total of 447 patients were diagnosed with a recurrence in 2017, 520 in 2018, 516 in 2019, 529 in 2020 and 80 up to February 2021. During the COVID-19 period a total of 449 patients were diagnosed with a SPBCs per 100, 000 breast cancer survivors, this was comparable to the 445 patients diagnosed per year per 100, 000 breast cancer survivors in 2017/2019 (p=0.91) (Table 1). The incidence of SPBCs was significantly lower during March-May 2020 compared to the same period in 2017/2019 (86 vs. 121) (p=0.03), leading to 50 less SPBCs diagnoses. The incidence was higher during June-August 2020 (124 vs. 95), however this was not significant (p=0.09). The incidence of recurrences in the COVID-19 period, and within all four subperiods, was comparable to the incidence in 2017/2019. Conclusion: The COVID-19 pandemic led to a decrease in the detection of SPBCs at the beginning of the pandemic. However, this drop in incidence was caught up in the period thereafter. This might be related to the restart of the regular follow-up visits (partly in real-life consultations), the call to go to the GP in case of complaints and the improved accessibility of the GPs. The incidence of recurrences did not decrease since it includes also DM, which cause worrisome symptoms for which care is sought.

Genomic testing on breast cancer core biopsy material is feasible and provides useful treatment information

Background: Genomic profiling assays for invasive breast cancer provide useful predictive and prognostic information and are performed most commonly on surgical resection specimens. Obtaining the molecular profile at the time of initial core needle biopsy is ideal because it could provide information that could significantly alter preoperative decision-making and avoid unnecessary treatments. In January 2020, the breast center began a 3 month pilot program that would reflexively send core biopsy material on all newly diagnosed patients for genomic testing using the MammaPrint (MPT) and BluePrint (BPT) assays regardless of receptor status. The goals were to determine feasibility and examine the impact to patient care. Methods: Breast core biopsy tissue was triaged by an attending pathologist as soon as slides were available. If invasive carcinoma with at least 3 mm in linear extent of tumor with 20% cellularity was identified, materials were immediately sent to Agendia for MPT/BPT testing even before ER/PR/HER2 testing was available to the pathologist. Clinicopathologic information, turn-around time (TAT) and adequacy data were tracked. The impact was discussed regularly at breast tumor board to determine if the results led to altered decision-making that could reduce unnecessary interventions and time to initial treatment. Results: 445 core biopsy specimens were sent for genomic testing. Of those 442, (97%) Syielded genomic results with an average TAT from biopsy to genomic result of 11 calendar days. MPT identified 233 (53%) cases that were low risk and 209 (47%) cases that were high risk. BPT showed that 60 (14%) cases were Basal, 18 (4%) cases were HER2, and 364 (82%) cases were Luminal. Further analysis of the Luminal subgroup demonstrated that 154 (42%) were Luminal A low risk, 78 (21%) were Luminal A Ultralow risk and 132 (36%) were Luminal B High Risk. Analysis by race demonstrated a significantly higher percentage of high risk tumors in African-American women including a higher percentage of basal cancers (26%) as compared to Caucasian women (10%). Of note, 51 patients in the pilot study had additional OncotypeDX (ODX) testing on subsequent surgical resection. There was fair correlation between the assays with the majority of the low risk MPT having low risk ODX scores (<=25) and the high risk MPT having high risk ODX scores (>25), though MPT identified more patients as being high risk. The COVID-19 pandemic altered plans to assess time to treat and treatment interventions as initially intended. However, the knowledge of genomic result enhanced the ability to triage patients, allowing those patients with low risk tumors to begin endocrine therapy and delay surgery. Use of preoperative hormone therapy was considered more often in place of neoadjuvant chemotherapy in patients with low genomic risk ER+/HER2-patients. Because of the continued feedback indicating positive impact, the pilot ultimately was extended to 11 months to allow time for formal implementation. Conclusions: Genomic testing using the MPT/BPT assay on core biopsy samples with at least 3 mm yields results 97% of the time with an average TAT of 11 days from biopsy date to result. The genomic information at the time of initial diagnosis impacted patient care most notably in the ER+ setting. The results led to the immediate implementation of direct reflex testing of all newly diagnosed ER+ and HER2-or IHC 2+ cancers by pathology after the initial pilot phase.

Neoadjuvant approach in patients with early breast cancer: evaluation of the breast cancer patient (patient assessment, staging, planning)

Neoadjuvant treatment (NAT) has become a standard treatment in locally advanced breast cancer and an option in early stage (stage I–II) breast cancer (EBC). It is known that patients who achieve a pathologic complete response (pCR) have better long-term out comes, especially Her2 positive and triple negative (TN) breast cancer. Selection of patients for NAT in early stage breast cancer rely in several factors, as patient characteristics (i.e., age and comorbid ities), tumor histology, stage at diagnosis and the potential changes in surgical or adjuvant treatments when NAT is administered. Early stage breast cancer patients that are not candidates for breast conservative surgery (BCS) at front, may benefit from NAT to reduce tumor size and facilitate surgery. In other cases, as young patients with TN tumors between 1–2 cm may benefit from NAT, even if BCS can be performed up front, as chemotherapy will be given anyway along the treatment and there is a high likelihood of pCR. Patients with a positive axilla at diagnosis, regardless of tumor size, may also benefit from less axillary surgery if axillary pCR is achieved. Rates of axillary pCR are especially high in TN and Her2 positive tumors. A distinct approach is suggested in luminal tumors subtypes. In these patients, besides the factors already mentioned, intensity of hormone receptor expression would help to decide on neoadjuvant hormone or chemotherapy treatment. Immunohistochemistry differentiation between luminal A and B by Ki67 assessment and in some cases, the use of genomic platforms may help defining type of NAT. Assessing breast cancer patients for NAT include incorporating all factors into the decision making process. In the COVID era, we have witnessed the use of NAT in patients who may be directed to surgery, unable to have it performed, as surgery has been reserved for emergency cases only. In this situation, it has been a great challenge managing breast cancer patients and tailoring individualized treatment decisions. Besides physical examination, breast imaging is performed to assess extent of disease and to determine BCS eligibility before NAT. Breast imaging should include mammogram with tomosynthesis, breast and axillary US and in most of cases MRI. MRI may be omitted in S12 Speakers’ s / The Breast 56S1 (2021) S1–S16 selected cases (i.e. fatty breasts, neoadjuvant hormone therapy). Contrast enhanced mammogram is an emerging technique, whether it will add accuracy to the MRI findings or replace it in selected cases is still to be defined. Shear wave elastography is under investigation for assessment of response to neoadjuvant therapy as well as for predicting response. Generally, in EBC no further body imaging (CT or bone scan) is needed unless metastatic disease is suspected. PET scan is reserved for patients with inconclusive metastatic dissemination or with more advanced disease. Pathology confirmation by core biopsy and evaluation of estrogen and progesterone receptor, Her2, and Ki67 must be obtained before treatment. Axillary US will characterize axillary lymph nodes and will guide biopsy of axillary nodes. If planning NAT, markers need to be placed in breast tumor/s and in biopsy proven positive axillary node. Same breast imaging should be repeated after NAT to assess response and to determine type of breast and axillary surgery. Sentinel lymph node biopsy after NAT is the preferred method. After NAT, surgical plan is delineated taking into account baseline characteristics, tumor response and patient desire. Conflict of Interest: Honoraria: Agendia. Advisory Board: Sirius medical.

Primary and secondary data analysis on the care situation of patients with venous thrombosis and cancer in Bavaria

Introduction: Cancer patients (pts) have a high risk of deep vein thrombosis (DVT) depending on the cancer type and risk factors. DVT-prophylaxis and anticoagulant therapy in cancer pts are challenging and often require a multidisciplinary diagnostic and treatment approach. Cancer associated thrombosis is the second leading cause of death in cancer pts. Patients' awareness of a potential DVT risk, relevant symptoms and the need for treatment compliance are important for optimal treatment. The BEQUEST study investigates, to what degree cancer pts are aware of their DVT-risk, who informs them, by whom and by what means DVT has been diagnosed/treated and if regional difference exist in Bavaria. Methods: The study follows a mixed methods design (quantitative and qualitative methods). Secondary claims data (KVB/ZI und AOK Bayern) will be used to determine treatment patterns, guideline adherence and associations between DVT treatment and outcomes. Through two pilot tested surveys (office-based physicians and pts) guideline acceptance, optimization potentials in multidisciplinary diagnostic/treatment, access to care facilities, awareness of side effects of cancer treatment, risk factors and DVT symptoms will be examined. Secondary data analyses and the patient survey will include pts of age > 18 with an active cancer (ICD- 10-GM: C00-99) diagnosis and an incident DVT (I.80). Results: In 2016-2018 approximately 38.000 pts suffered from cancer and an incident DVT in Bavaria. The main underlying diseases are neoplasms of breast, prostate, without specific localization and of gastrointestinal tract. Secondary data analyses are ongoing and are expected to be finalized end of June 2021. Even though patient survey was delayed due to the Covid-19 pandemic it is currently online and will be analyzed by the time of the DGHO annual meeting. The physicians' survey is postponed because of the involvement of office based physicians in the Covid-19 vaccination campaign. Conclusions: The results will show whether medical care in urban compared to rural areas is different and whether it correlates with outcomes of cancer pts with DVT. The patient survey will indicate the accessibility to facilities, if pts are aware of risks/side effects of their cancer disease and which information source they use. The physician survey will highlight whether there are improvement suggestions of the reimbursement structure and possibilities to optimize the treatment of cancer pts with DVT.