Isopp 2023

The proceedings contain 109 papers. The topics discussed include: dose intensity of palbociclib and initial body weight dosage: implications on progression free survival in 220 patients with ER+/HER2-negative metastatic breast cancer;characteristics of Nirmatrelvir/Ritonavir (Paxlovid) recipients and clinical interventions by oncology pharmacists at a tertiary outpatient cancer center;safe handling of non-carcinogenic drugs in the Ghent University Hospital: development, implementation and communication of hospital-specific guidelines;case series: use of olaparib in uncommon locations in patients with impaired homologous recombination;real-world data evaluation of medicines used in special situations in oncohematology: a retrospective study from a comprehensive cancer institution;Dostarlimab in the treatment of recurrent endometrial cancer: real life experience;medication-related osteonecrosis of the jaws and CDK4/6 inhibitors in breast cancer;and efficacy and safety outcomes of generic imatinib in adults with chronic myeloid leukemia (CML) following the switch from branded imatinib.

Gene Editing/Gene Therapies: CHALLENGE TO DEVELOP GMP COMPLIANT MANUFACTURING PROCESS FOR COXSACKIE VIRUS TYPE B3

Background & Aim: Gene therapies has become recognized for its remarkable clinical benefits in a variety of medical applications, in particular recent approval of an Ad vector-based COVID-19 vaccines have attracted recent global attention. Here, we present key considerations for GMP compliant process development for Coxsackie virus type B3 (CVB3), an oncolytic virus designed for clinical trial in triple-negative breast cancer. Methods, Results & Conclusion(s): CVB3 is a non-enveloped, linear single-strand RNA virus with a size of approximately 27-33 um in diameter. From the initial type using the zonal rotor centrifuge to the advanced type using the tangential flow filtration system and ion chromatograph, we considered the points of the design concept in constructing the manufacturing process. The final design system is constructed as a closed and single-use manufacturing system in which all processes from upstream large-scale cell culture to downstream target purification and concentration steps. In brief, HEK293 cell suspension extended in 3L serum-free medium infected with CVB3, up to 3.6 times 10 to 7 of TCID50 /mL before going to downstream steps, made total 150 mL of final products as 8.43 times 10 to 7 of TCID50/mL concentration. Although further quality control challenges remain that is removal of product-related impurities such as human cellular proteins and residual DNA/RNA to increase virus purity, this concept is effectively applicable even for other types of viruses as GMP manufacturing processes, and would be also important for technology transfer to future commercial production.Copyright © 2023 International Society for Cell & Gene Therapy

DIAGNOSIS OF MEDICAL CONDITIONS IN PATIENTS USING MACHINE LEARNING MODELS

A variety of patient care and intelligent health systems can benefit from the implementation of artificial intelligence as a tool to aid caregivers. Machine learning and deep learning are two types of AI that are increasingly being used in the medical industry. Artificial intelligence methods require a large amount of clinical data from a range of imaging modalities for correct disease diagnosis. In addition, AI has greatly enhanced the quality of hospital stays, allowing patients to be released sooner and complete their recoveries at home. This article aims to provide the information on the field of AI subset i.e., machine learning-based disease detection with information that will aid them in making better decision making. This helps the researchers to classify the medical conditions in patients with a prominent dataset.

Short Term Outcome of Management of Early Breast Cancer Patients in COVID-19 Era. Ain Shams University Experience

Introduction: COVID-19 implied that a great number of infected individuals were hospitalized and possibly admitted to intensive care units. Cancer centers have rapidly changed models of care by delaying non-urgent surgeries. Breast surgeries were delayed for early breast cancer patients forcing clinicians to potentially alter treatment recommendations by neoadjuvant chemotherapy until appropriate conditions were established. Aim of the work: to assess conservative breast cancer surgery after neo-adjuvant therapy in early breast cancer patients in COVID-19 era as regard surgical outcome, complications and early recurrence comparing results with previous results when patients underwent primary conservative breast surgery. Patients and Methods: This is a cohort study that was conducted 52 patients with early breast cancer stage I and II a. Patients were divided into two groups (A) and (B). Group A included 26 patients who underwent primary conservative breast surgery. Group B included 26 patients who underwent conservative breast surgery after neo-adjuvant therapy during COVID-19 era. Results: Intra-operative re-excision was done in 5 patients (19.2%) in group A and 3 patients (11.5%) in group B. Two patients (7.7%) in group A and 1 patient (3.8%) in group B were converted to modified radical mastectomy. Sentinel lymph node (SLN) was done in all 26 patients in group A while only 25 patients in group B with 1 patient undergoing axillary dissection from the start. SLN was positive in 8 patients (30.8%) in group A & 6 (24 %) patients in group B. Consequently, 8 patients (30.8%) in group A and 7 patients (26.9%) in group B underwent axillary dissection. Conclusion: Conservative breast cancer surgery after neo-adjuvant therapy in early breast cancer patients in COVID-19 era has comparable results to primary conservative breast surgery. Thus, the obligatory decision to delay primary surgery during COVID-19 era by giving neoadjuvant chemotherapy was effective. Copyright © Celsius Publishing House.

Reducing your risk cancer-focused health events to meaningfully engage the medically underserved and diminish future cancer disparities

Lack of access to cancer prevention education, early screening, and timely treatment, particularly in low socioeconomic, underserved communities, are cited as substantial barriers to improving survivorship. Outreach educational efforts with on-site screenings offered in partnership with community groups are known to be valuable in encouraging community members' uptake of healthy behaviors and adherence to screening recommendation. To create more engaging events, a community-academic partnership, We Engage 4 Health (WE4H), co-created 11 unique 4-panel comic-style stories designed to be read aloud together as attendees visit each event table. These colorful stories are shared on boards that stand on each table and are offered in both English and Spanish at this time. Many tables also have an accompanying hands-on activity. Together, they lead to meaningful "low stakes" discussions which support understanding of seemingly complex health information. Story topics include the cause of cancer (Cells Gone Wrong), cancer risk factors (Reducing Your Risk), the role of primary care in cancer screening (Primary Care for Prevention), the purpose of research (short Research Ready) and details about specific cancer types (Combatting Colon Cancer, Blocking Breast Cancer, Looking for Lung Cancer, Silencing Skin Cancer, Hindering HPV, and Professional Prostate Protection) and COVID-19 (Take Your Best Shot FAQs). A health passport is used to facilitate table visitation and survey collection at each table enables meaningful evaluation of the event as well as provides the community hosts and their partners baseline cancer data to inform future programing. In 2022, WE4H and the University of Cincinnati Cancer Center partnered with three different communities to co-host pilot events that served over 100 adult residents. Community, research interns and university students volunteered to work the tables at the event and received training prior. Post event surveys and discussions indicated that community partners appreciated the different take on a health fair event. Most volunteers indicated that they would enjoy volunteering again. Attendees indicated that they liked the graphic-style story format used and most preferred it to text and text with graphics approaches. Taken together, the data indicates that Reducing Your Risk events are useful in meaningfully engaging hard to reach, at risk attendees. Additional in-person and virtual events are being planned for 2023 as an approach to reach the medically underserved throughout our region.

The mediating effects of socio-behavioral factors on the needs for help among Asian American breast cancer survivors

Background: Breast cancer survivors often report their high needs for help during the transition to cancer survivorship. During the COVID-19 pandemic, technology-based programs are increasingly popular because of their high flexibility and accessibility in delivering information and coaching/support to address the current needs for help among cancer survivors. Yet, little is known about how socio-behavioral factors influence the effects of a technology-based intervention on the needs for help of racial/ethnic minority breast cancer survivors, especially Asian American breast cancer survivors. Purpose(s): The purpose of this secondary analysis was to examine the multiple socio-behavioral factors (including attitudes, self-efficacy, perceived barriers, and social influences related to breast cancer survivorship) mediated the effects of a technology-based intervention on the needs for help among Asian American breast cancer survivors. Method(s): This analysis was conducted with the data from 199 Asian American breast cancer survivor women who were recruited from January 2017 to June 2020 through online and offline communities/groups. The needs for help were measured using the Support Care Needs Survey-34 Short Form (SCNS) with five domains on psychological, information, physical, support, and communication needs. Mediation analysis was conducted using the PROCESS macro within SPSS. The analysis determined the mediating effects of four socio-behavioral mediators on the needs for help at pre-test [T0 ], post 1-month [T1 ], and post 3-months [T2 ] of a technology-based intervention. Result(s): Overall, all the mediators had statistically significant mediation effects on all types of needs for help (p < .05) at different points. Attitudes and social influence presented statistically significant mediation effects on the total needs for help score over 3 months (T0 , T1 , and T2 ). Perceived Barriers had mediation effects on all types of needs for help over 1 month (T0 , T1 ). Self-efficacy mediated the effects on all types of needs for help only at post 1 month (T1 ). Conclusion(s): The findings supported that all the socio-behavioral factors (attitudes, self-efficacy, perceived barriers, and social influences) mediated the effects of a technology-based intervention on the needs for help of Asian American breast cancer survivors. Future research and practice should consider socio-behavioral factors to reduce their needs for help during their survivorship process.

Sensitizing breast cancers to immune checkpoint inhibitors through CD27 agonism and vaccination against tumor-associated antigen

Project objective: Despite the recent revolution in immune checkpoint inhibitors (ICIs), only modest improvement in overall survival and likely caused by not enough potent cellular immunity among BC patients. Our lab has been focus on inducing cellular immunity against HER2+ BC through vaccination against the tumor-associated antigen HER2. Approximately 20 years ago, we performed an experimental pilot study by administrating HER2 peptide and recombinant protein pulsed dendritic cells (DC vaccine) to six patients with refractory HER2+ advanced or metastatic (stage II (>= 6 +LN), III, or stage IV) BC. We followed the patients on 2019 found that all of the six patients were still alive, 18 years after vaccination. Their blood sample were analyzed with cytometry by time-offlight (CyTOF) and found there is a significantly increased presence of CD27 expressing memory T cells in response to HER2 peptide stimulation. Recent report on the SARS-CoV2 mRNA vaccine also suggested that CD27 expressing memory T cells plays a critical role in long-lasting cellular immunity against SARS-CoV2 infection. Therefore, we hypothesized that CD27 plays a critical role in cellular immunity against BC, and the stimulation of CD27 expressing T cells with mAb targeting CD27 significantly increase the cellular immunity triggered by vaccination against tumor-associated antigen. Result(s): We recapitulate the rise of CD27+ antigen specific T cells among the vaccinated patients using a transgenic mouse model expressing human CD27. When combined the adenoviral-vector based HER2 (Ad-HER2) vaccination with a single dose of human aCD27 antibody (Varlilumab), we found there is a robust increase in the HER2 specific T cells compared to vaccination alone, especially CD27+CD44+ memory CD4 T cells, even after 120 days post vaccination. Using an ICIinsensitive syngeneic HER2+ BC models, we found 50% of mice in the combination group of aCD27 antibody plus Ad-HER2 showed total tumor regression by the end of study. When combined with anti-PD1 antibody, the combination of AdHER2 and Varlilumab leads to total tumor regression in 90% of tumor bearing mice with syngeneic HER2+ BC, indicating that the vaccination against tumor associated antigen HER2 plus anti-CD27 antibody sensitized ICI-insensitive HER2+ BC toward ICI. Conclusion(s): Our data demonstrates that the administration of anti-CD27 antibody significantly increase the long term presence of CD27+ antigen specific memory T cells after vaccination against tumor associated antigen HER2. As consequence, combination of anti-CD27 with HER2 sensitized the immune unresponsive breast cancer toward anti-PD1 antibody. Our study suggests that the vaccination against tumor-associated antigen with mAb targeting CD27 leads to the robust cellular immunity, which is required for successful ICIs against breast cancer.

The relationship between inflammatory diet score and cancer-specific outcomes: Systematic review and meta-analysis

Cancer remains one of the most prevalent diseases in the United States and a leading cause of death. Large prospective studies have found significant correlations between dietary intake and cancer. Chronic inflammation promotes pro-cancer inflammatory environments and nutrition can influence inflammation, with the intake of certain food items increasing inflammatory biomarkers. The objective of this research was to explore the relationship between inflammatory diet score measured by the Dietary Inflammatory index and all-cause mortality, cancer-specific mortality, and cancer recurrence among cancer survivors. Web of Science, Medline, CINHAL, and PsycINFO databases were searched to collect potentially eligible sources that focus on dietary inflammation and cancer outcomes. All sources were uploaded to Covidence software and screened by two independent blinded reviewers. The quality of the sources was assessed using the Newcastle Ottawa scale and relevant data was extracted and transferred to the Comprehensive Meta Analysis software and a random effects model was used to perform meta-analysis. Of the 1444 studies imported into the Covidence software, 13 passed all the screening stages and were included in the final analysis. Eight studies reported on pre-diagnosis diet while five others reported on postdiagnosis diet. Five studies reported on colorectal cancer, four on breast cancer, two on ovarian cancer, one on endometrial cancer and one on prostate cancer. Meta-analysis of the studies found that being in the highest postdiagnosis DII score indicating pro-inflammatory diet significantly increased the risk of all-cause death among cancer survivors by 33.5% (HR = 1.335, 95% CI = 1.049, 1.698, n = 6). Analysis did not show a statistically significant association between DII score and cancer mortality or recurrence (HR = 1.097, 95% CI = 0.939, 1.281, n = 6). Analysis by cancer subtype found a significant correlation between postdiagnosis DII score and all-cause mortality among the breast cancer survivors (HR = 1.335, 95% CI = 1.041, 1.711, n = 3) though there were no significant associations between DII and the outcomes of interest from the other cancer types. The meta-analysis concludes that being in the highest postdiagnosis DII score group significantly increased the risk of all-cause death among cancer survivors. This suggests that risk of all-cause mortality could be reduced for cancer survivors by consuming more anti-inflammatory food components and reducing consumption of pro-inflammatory foods. These findings also warrant more research in this field to clarify the relationship between dietary inflammation as measured by the DII and cancer outcomes, particularly cancer-specific mortality.

Empirical Review of Various Thermography-based Computer-aided Diagnostic Systems for Multiple Diseases

The lifestyle led by today's generation and its negligence towards health is highly susceptible to various diseases. Developing countries are at a higher risk of mortality due to late-stage presentation, inaccessible diagnosis, and high-cost treatment. Thermography-based technology, aided with machine learning, for screening inflammation in the human body is non-invasive and cost-wise appropriate. It requires very little equipment, especially in rural areas with limited facilities. Recently, Thermography-based monitoring has been deployed worldwide at various organizations and public gathering points as a first measure of screening COVID-19 patients. In this article, we systematically compare the state-of-the-art feature extraction approaches for analyzing thermal patterns in the human body, individually and in combination, on a platform using three publicly available Datasets of medical thermal imaging, four Feature Selection methods, and four well-known Classifiers, and analyze the results. We developed and used a two-level sampling method for training and testing the classification model. Among all the combinations considered, the classification model with Unified Feature-Sets gave the best performance for all the datasets. Also, the experimental results show that the classification accuracy improves considerably with the use of feature selection methods. We obtained the best performance with a features subset of 45, 57, and 39 features (from Unified Feature Set) with a combination of mRMR and SVM for DB-DMR-IR and DB-FOOT-IR and a combination of ReF and RF for DB-THY-IR. Also, we found that for all the feature subsets, the features obtained are relevant, non-redundant, and distinguish normal and abnormal thermal patterns with the accuracy of 94.75% on the DB-DMR-IR dataset, 93.14% on the DB-FOOT-IR dataset, and 92.06% on the DB-THY-IR dataset. [ FROM AUTHOR] Copyright of ACM Transactions on Intelligent Systems & Technology is the property of Association for Computing Machinery and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Liquid biopsy testing in metastatic or advanced breast cancer patients during the COVID-19 pandemic

Objective: During the COVID-19 pandemic, cancer patients had restricted access to standard of care tissue biopsy. Liquid biopsy assays using next generation sequencing technology provides a less invasive method for determining circulating tumour mutations (ctDNA) associated with targeted treatments or prognosis. As part of deploying technology to help cancer patients obtain molecular testing, a clinical program was initiated to offer liquid biopsy testing for Canadian patients with advanced or metastatic breast cancer. Method(s): Blood was drawn in two 10 mL StreckTM DNA BCTs and sent to the CAP/CLIA/DAP accredited Imagia Canexia Health laboratory for testing using the clinically validated Follow ItTM liquid biopsy assay. Plasma was isolated using a double spin protocol and plasma cell-free DNA (cfDNA) extracted using an optimized Promega Maxwell RSC method. Extracted cfDNA was amplified using the multiplex amplicon-based hotspot 30 or 38 gene panel and sequenced. An inhouse developed bioinformatics pipeline and reporting platform were used to identify pathogenic single nucleotide variants (SNVs), indels (insertions and deletions), and gene amplification. Included in the panel are genes associated with metastatic breast cancer: AKT1, BRAF, ERBB2, ESR1, KRAS, PIK3CA, TP53. Result(s): To identify biomarkers, 1214 metastatic or advanced breast cancer patient cfDNA samples were tested. There were 15 cases sent for repeat testing. We reported 48% of samples harboring pathogenic ctDNA mutations in TP53 (22%), PIK3CA (19%), ESR1 (18%), AKT1 (2%), ERBB2 (1.5%). Co-occurring variants were identified in samples with ESR1/PIK3CA as well as TP53/PIK3CA (both p-values <0.001). Interestingly, 29% of samples with mutated ESR1 harbored >= 2 ESR1 ctDNA mutations. In 56% of cases, previous molecular testing indicated the cancer subtype as hormone receptor (ER, PR) positive with/without HER2 negative status. In this specific subgroup, 49% harbored ctDNA mutations with 63% of those being PIK3CA and/or ESR1 mutations. Conclusion(s): A population of Canadian women with metastatic breast cancer were tested using a liquid biopsy gene panel during the COVID-19 pandemic for identification of biomarkers for targeted therapeutic options. Over 50% of the samples were identified as hormone positive, with greater than 60% harboring PIK3CA and ESR1 ctDNA mutations. Studies have shown that metastatic PIK3CA mutated ER-positive/HER2-negative tumors are predictive to respond to alpelisib therapy and have FDA and Health Canada approval. Additionally, ESR1 mutations are associated with acquired resistance to antiestrogen therapies, and interestingly we identified 29% of ESR1 mutated samples with multiple mutations possibly indicating resistance subclones. In future studies, longitudinal monitoring for presence of multiple targetable and resistance mutations could be utilized to predict or improve clinical management.

MicroRNAs: The Master Regulators of the Breast Cancer Tumor Microenvironment

Breast cancer is the most commonly diagnosed cancer globally and is among the leading causes of cancer deaths worldwide. Breast cancer mortality rates are increasing due to delays in diagnosis, prognosis, and treatment caused by the coronavirus disease 2019 (COVID-19) pandemic. Identification and validation of blood-based breast cancer biomarkers for early detection is a top priority worldwide. MicroRNAs (miRNAs) show the potential to serve as breast cancer biomarkers. miRNAs are small, endogenously produced RNAs that regulate growth and development. However, oncogenic miRNAs also play a major role in tumor growth and can alter the tumor microenvironment (TME) in favor of cancer metastasis. The TME represents a complex network of diverse cancerous and noncancerous cell types, secretory proteins, growth factors, and miRNAs. Complex interactions within the TME can promote cancer progression and metastasis via multiple mechanisms, including oxidative stress, hypoxia, angiogenesis, lymphangiogenesis, and cancer stem cell regulation. Here, we decipher the mechanisms of miRNA regulating the TME, intending to use that knowledge to identify miRNAs as therapeutic targets in breast cancer and use miRNAs as blood-based biomarkers. © Springer Nature Singapore Pte Ltd. 2022.

Management of COVID-19 Infection and Midwifery Care of a Woman with Breast Cancer-A Case Report

Breast cancer is one of the most common types of cancer in women and its incidence in pregnancy is 1/3000. After the emergence of the COVID-19 pandemic, it has created a high risk factor for cancer patients as well as affecting the society. The situation is similar in the process of breast cancer. Despite the fact that cancer patients are risk factors, their follow-up and follow-up will not be interrupted, which will allow them to maintain their current status. The prolongation of the treatment period of the patients complicates the process they are in. In this case, the follow-up period of the patient who was diagnosed with breast cancer in the third trimester of his second pregnancy during the COVID-19 period was discussed. The frequency of follow-up during the postpartum COVID-19 period of the case decreased, and therefore, recurrence was experienced. In cases such as disasters and pandemics, cancer patients should be supported in terms of both physical and mental health. During the follow-up process, patients should be guided in their public health follow-ups, and the frequency of examinations and follow-up processes should be reminded. Midwife-assisted care should be provided during these follow-ups. © 2022, Universitas Negeri Semarang. All rights reserved.

Measuring the impact of the COVID-19 pandemic on breast cancer screening in Puerto Rico

Introduction: The COVID-19 pandemic has caused major changes to healthcare services, especially those related to early detection and screening practices like breast cancer. In Puerto Rico, breast cancer is the main cause of death, representing 18.9% of cancer deaths in women, making early detection even more important to prevent morbidity and mortality. This study aims to describe the impact of COVID-19 on breast cancer screening and assess differences in health utilization by age group and health regions in Puerto Rico. Method(s): This study used data on breast cancer screening medical claims from Puerto Rico Track, a project in collaboration with the Puerto Rico Public Health System and the Puerto Rico Institute of Statistics that aims to assess health access and utilization patterns in Puerto Rico. Claims including unilateral and bilateral mammography, sonommamography, and MRI were analyzed. Descriptive statistics and percentual changes between the COVID-19 baseline year (2016) compared with 2020 and 2021 were performed (overall, by age-group and health region). Result(s): A total of 193,793 screening tests were performed in 2016, compared to 66,463 in 2020, and 89,322 in 2021. Overall, a third of the medical claims for breast cancer screening (33.2%) were in the age group of 51-60 years. An overall decreasing percentual change was observed comparing 2016 vs. 2020 (65.7%), where the age group with the broadest gap reduction were among women 41-50 years old (68.2%). When comparing medical claims of 2016 (193,750) versus 2021 (89,320) (pre and post pandemic), an important decreasing change (53.9%) was observed. The age group with the highest decrease comparing 2016 to 2021 was the 41-50 years one (68.2%). The Western region of Mayaguez/Aguadilla had the highest decreasing percentual change, with a reduction of 73.6% in 2020 compared to 2016, and 62.6% when compared 2021 with 2016. Conclusion(s): Breast cancer screening was notably affected by the COVID-19 pandemic in Puerto Rico. A pattern of decreasing breast cancer screening was observed by health regions and by age. These efforts provide evidence of the need of tailored evidence-based interventions to increase breast cancer screening in the island.

Viruses and the risk of lung cancer: prevention and treatment

Lung cancer is the most common cancer in males and the second most common among females both in Europe and worldwide. Moreover, lung cancer is the leading cause of death due to cancer in males. The European region accounts for 23% of total cancer cases and 20% of cancer-related deaths. Relationships have been described between a number of infectious agents and cancers, but our knowledge of the role of viruses, both respiratory and systemic, in the pathogenesis of lung cancer is still rudimentary and has been poorly disseminated. In this chapter, we review the available evidence on the involvement of HPV, Epstein-Barr virus, HIV, cytomegalovirus and measles virus in the epidemiology and pathogenesis of lung cancer.Copyright © ERS 2021.

Pulmonary influenza infection promotes the awakening of dormant metastatic breast cancer cells

Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. The most common sites of metastatic breast cancer are bone, liver and lung. Respiratory viral infections inflict illnesses on countless people. The latest pandemic caused by the respiratory virus, SARS-CoV-2, has infected more than 600 million worldwide, with documented COVID-related death upward of 1 million in the United States alone. Respiratory viral infections result in increased inflammation with immune cell influx and expansion to facilitate viral clearance. Prior studies have shown that inflammation, including through neutrophils, can contribute to dormant cancer cells reawakening and outgrowth. Moreover, inhibition of IL6 has been shown to decrease breast cancer lung metastasis in mouse models. However, how respiratory viral infections contribute to breast cancer lung metastasis remains to be unraveled. Using MMTV/PyMT and MMTV/NEU mouse models of breast cancer lung metastasis and influenza A virus as a model respiratory virus, we demonstrated that acute influenza infection and the accompanying inflammation and immune cell influx awakens and dramatically increased proliferation and expansion of dormant disseminated cancer cells (DCC) in the lungs. Acute influenza infection leads to immune influx and expansion, including neutrophils and macrophages, with increased proportion of MHCII+ macrophages in early time points, and a sustained decrease in CD206+ macrophages starting 6 days post-infection until 28 days after the initial infection. Additionally, we observed a sustained accumulation of CD4+ T cells around expanding tumor cells for as long as 28 days after the infection. Notably, neutrophil depletion or IL6 knockout reversed the flu-induced dormant cell expansion in the lung. Finally, awakened DCC exhibited downregulation of vimentin immunoreactivity, suggesting a role for phenotypic plasticity in DCC outgrowth following viral infection. In conclusion, we show that respiratory viral infections awaken and increase proliferation of dormant breast cancer cells in the lung, and that depletion of neutrophils or blocking IL6 reverses influenza-induced dormant cell awakening and proliferation.

The Impact of COVID-19 on Breast Cancer Treatment: A Systematic Review

Background: During the COVID-19 pandemic, health resources were stretched, access was impacted by lockdowns and there were concerns about exposure to the virus during visits to hospitals. The purpose of this study was to examine how breast cancer treatments (presentation, surgery, radiotherapy, chemotherapy and/or endocrine therapy) changed or were adapted during the early phase of the pandemic. Methods: A systematic review was conducted using PRISMA guidance. Eligible studies presented original data reporting changes to early breast cancer treatment by comparing ‘pandemic' treatment to a ‘pre-pandemic' cohort or to ‘ideal' treatment of individual cases. Data were extracted into evidence tables and narrative synthesis was used to analyze results. Results: Fifteen studies with paired design were eligible. These reported outcomes for 6,353 people treated for early breast cancer (January 2020–June 2021). All studies reported some change to treatment due to the pandemic. The nature of reported changes was inconsistent. Changes included: more advanced tumours at presentation compared to pre-pandemic, an increase in breast conserving surgery;an increase in simple mastectomy (without breast reconstruction);a trend towards increased wait times, delays to start of treatment, shorter post-operative hospital stay and hypofractionation or omission of radiotherapy. Centres used more or less neoadjuvant chemotherapy or endocrine therapy. Conclusion: In the early stage of the pandemic, fewer early-stage breast cancer cases were treated at many centres. Treatment for breast cancer was impacted and various local solutions were developed. These included less complicated breast surgery, increased use of neoadjuvant therapy, and changes to radiotherapy regimens. Surgery was frequently delayed and breast reconstruction was often unavailable. These results have implications for breast cancer services during the pandemic recovery as a ‘catch-up' increase in cancer diagnoses is expected. Women may wish to access breast reconstruction, unavailable due to COVID-19. The impact of changes to treatment on long-term quality of life should be evaluated. © The Author(s) 2022.

Inflammatory biomarkers: Breast cancer survival and possible role in COVID-19 associated comorbidity

It is known that inflammatory cytokines exacerbate the persistence and severity of various disease states. Breast cancer is the most frequently detected cancer among women worldwide and our recent studies suggest that the inflammatory state of breast (BrCa) cancer, a byproduct of elevated cytokine expression, induces epigenetic modifications leading to increased recurrence. Ongoing NCI clinical trial data (ClinicalTrials.gov, CCC19, NCT04354701) indicates that among patients with cancer and COVID-19, the mortality is high, and the most prevalent malignancies are of breast [21%] and prostate [16%] origin. Due to the risk of cytokine storm during SARS-CoV-2 infection, it is crucial to identify potential mechanisms of hyperinflammation in BrCa patients. In this study, we have evaluated the level of copy number alteration (CNA) of different inflammatory cytokines including IL-8, IL-1b, IL6, IL-8, GM-CSF, TNF-alpha and many others using cBioportal platform which includes over sixty-nine thousand tumor samples (n>69,000 from 213 different studies) from over 33 different cancers. We found that IL-8 has the highest level of amplification in different breast cancers subtypes. Besides, we also analyzed serum samples from BrCa patients, both recurrent and non-recurrent, by different proteomics methods to identify serum cytokines involved in prognosis and recurrence. Comparative data analysis between non-recurrent BrCa against recurrent BrCa patients identified several proteins with very high significance, mostly proteins associated with epigenetic pathways including HDAC9 (P = 0.0035), HDAC5 (P = 0.013), and HDAC7 (P = 0.020). Besides, we identified differential expression of several pro-inflammatory cytokines and immune regulators (IL-8, IL-4, IL-18, IL-12p70) that were present only in recurrent BrCa patient serum. Our data indicate that inflammatory processes contribute to epigenetic modifications that ultimately play a critical role in breast cancer recurrence. In terms of COVID-19 associated co-morbidity, the already dysregulated inflammatory state of BrCa patients may increase their susceptibility to cytokine-storm, leading to increased severity of COVID-related complications and increased mortality rate. Specifically, we hypothesize that the identified elevated level of IL-8 in BrCa patients may lead to a higher basal level of inflammation and contribute to the risk of attaining cytokine-storm during SARS-CoV-2 infection, making it a valuable target for future studies.

Impact of COVID-19 on longitudinal breast cancer research studies involving TNBC patients

Background Triple-negative breast cancer (TNBC) accounts for ~15% of breast cancer diagnoses but is linked to worse outcomes and comprises a disproportionate number of breast cancer deaths. The TNBC pilot study is a prospective longitudinal study to provide a critical resource for understanding TNBC disease. However, the pandemic impacted the collection of samples. Objective To highlight the impacts of COVID-19 on this longitudinal cancer translational research study including the patient's perspective and to develop recommendations to avoid future disruptions. Methods 389 participants were enrolled in the prospective longitudinal cohort, which collected serial blood samples for up to 5 years. Due to the pandemic, research was curtailed for 6 months due to concerns about patient safety, halting the collection of blood samples. Missed samples and data gaps were documented. To complement this, we initiated a survey capturing the patient perspective on their experience of the study disruption due to COVID. Results 217 enrolled participants missed a blood draw or had a collection outside the study window. 158 patients missed 1 time-point collection, and 59 patients missed >= 2 collections. Of the 217 participants who missed a collection, 6 disease recurrence diagnoses and 3 deaths occurred during research curtailment. The collection of survey responses from participants is ongoing and will be presented at the AACR Annual Meeting. Conclusion Missed samples resulted in irreplaceable data gaps critical to monitoring patient outcomes, and reduced cohort sampling during the pandemic. Our current knowledge of the risks suggests that with proper informed consent, collections could have continued. To mitigate disruption in future clinical studies, clear plans should be part of study design to provide continuity. The participants' experience to be reported will also help researchers understand their issues and help develop policies. (Table Presented).