Search

Introduction: There is an increased need to monitor and intervene to assist breast cancer (BC) survivors overcome the long-term and late effects of treatment. Many institutions are moving toward computerized assessments (CA) of PROs such as symptoms and concerns in place of more traditional paper and pencil administration, but little work has been performed to demonstrate that these very different methods of administration produce comparable results. Our goal was to evaluate the outcomes produced by these methods by comparing two similar samples of breast cancer survivors, one of which completed a PROs assessment using paper and pencil (PP), the other of which was assessed using a computerized system that links to the patient portal in use at our facility. Data collection of the CA of PROs is ongoing. Method: Women were eligible if they had a confirmed diagnosis of Stage 0-III BC, were within one year of completion of primary therapy, and were scheduled for a survivorship-focused end of treatment visit. As this was a naturalistic cohort study, no randomization was undertaken. The PRO assessment covered 19 common long-term or late effects of treatment, inquiring about their occurrence and severity in the previous month. On the day of the visit, participants in the PP cohort were provided with the questionnaire packet to complete prior to meeting with their provider. The women who completed the CA were either already enrolled in the patient portal or enrolled at the time of recruitment and sent an online version of the same questionnaire. Reminder calls and/or emails were sent to the CA participants to improve compliance. Results: 164 BC survivors completed the PP questionnaire, and 62 women completed the CA. Racial make-up, marital status, and education, were similar between groups. Women in the PP group were older than those in the CA group (55.45 vs. 51.23 yrs, p < 0/05) and those in the PP group were marginally more likely than those in the CA group to have been menopausal prior to treatment (50% vs. 35%, p = 0.05). With respect to PROs, there were no significant differences between groups in either the proportion of women endorsing a given symptom/concern or in the mean severity rating for any symptom/concern. The five most commonly reported concerns did differ somewhat between groups, with PP reporting Fatigue, Insomnia, Hot Flashes, Aching Joints, and Memory Difficulties, respectively, and CA reporting Fatigue, Anxiety, Body Image Problems, Memory Difficulties, and a tie between Insomnia and Depression, respectively. Conclusion: The results of the PRO assessment can be assumed to be comparable whether the method of administration is either PP or computerized. Differences found between groups in the most commonly endorsed symptoms likely reflected differences in age and menopausal status. Citation Format: Palmer SC, DeMichele A, Glanz K, Schapira M, Pucci DA, Blauch AN, Jacobs LA. Comparability of computerized and paper-pencil patient reported outcome (PRO) assessments – Does it matter how they are administered?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-11.

The lack of reproducibility of preclinical research is a significant and growing problem which slows basic research and leads to fruitless clinical trials. An increasing number of reports have found discrepancies in published preclinical studies across scientific disciplines. For example: * Amgen found that 47 of 53 “landmark” oncology publications could not be reproduced. * Bayer found that their internal results contradicted academic publications in 43 of 67 oncology and cardiovascular projects. * Dr. John Ioannidis and his colleagues found that of 432 publications purporting sex differences in hypertension, multiple sclerosis, or lung cancer, only one data set was reproducible. These studies, and the many others that report similar results, highlight a significant problem in the development of new therapies to treat disease. With increasing reports of discrepancies in preclinical publications, pharmaceutical companies are being forced to re-evaluate their reliance on academic research. In fact, Bayer recently decided to halt nearly two-thirds of target-validation projects.In this session, we'll report the work we have done to address this issue. We will bring together researchers and representatives from funders and publishers to discuss the issue of reproducibility. We will share funder and publisher initiatives to promote reproducibility and also discuss research practices that lead to more reproducible research such as using proper statistical tests, reporting all experimental data, experimental blinding, and identification and validation of research reagents. We'll also share preliminary results from an Arnold Foundation-funded study to replicate the 50 most high impact cancer biology studies from 2010-1012. Reproducibility ResearchAmgen47 of 53 “landmark” oncology publications could not be reproducedBayerinternal results contradicted academic publications in 43 of 67 oncology and cardiovascular projectsDr. John Ioannidis and colleagues432 publications purporting sex differences in hypertension, multiple sclerosis, or lung cancer, only one data set was reproducible Note: This abstract was not presented at the meeting. Citation Format: Gunn William, Elizabeth Iorns, Elizabeth Silva, Brian Nosek. Preliminary results from the Reproducibility Project: Cancer Biology - a replication of 50 high-impact cancer cell biology papers from 2010-2012. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5053. doi:10.1158/1538-7445.AM2014-5053

Background: The healthcare system has extremely large volumes of patients' paper medical records (PMRs) scattered throughout various medical facilities. Currently the industry is transitioning to Electronic Medical Records (EMR). Although each source of information is equally important, a complete longitudinal health record is rarely available or currently attainable. The goal of this effort is to convert the existing PMRs into searchable electronic equivalents and merge them with existing EMRs to create a more complete longitudinal health record to support clinical care and biomedical research.Method: Using a subset of PMRs for subjects enrolled in the Clinical Breast Care Project at Walter Reed Army Medical Center, (WRAMC), we are developing an automated method to digitize and index the records, extract the biomedical information and prepare the data for delivery to clinicians and researchers. The electronic records were loaded into a database for immediate access by clinicians. To support translational research, MRs need to be de-identified, and information extracted and loaded into a research database; we used ten MRs to develop the operational method. Several methods were tested in the de-identification process: 1) manually, by striking out the protected health information (PHI) on paper before it was digitized and 2) “electronically”, by redacting the record electronically on the computer after it was digitized. We are in the process of testing automated data extraction tools and natural language processors to automatically de-identify and extract data from the EMR.Result: We quickly realized that only 10% of PMRs existed onsite at WRAMC; remaining MRs were held by the patients or other medical facilities. Approximately 300 PMRs, containing 66,600 pages, were scanned and digitized for this project. We have created a successful digitization process, which includes creating PDFs with hidden and searchable information. We have compared the effort and accuracy of various redaction methods. To de-identify 10 records, it took ∼10 hours manually and ∼20 hours electronically. It took longer electronically because of the preparations to ensure the removed information could not be retrieved. We expect that automated redaction tools will greatly reduce that effort. We also found that the electronic method had a 99% accuracy compared to 96% for the paper method. A portal prototype to allow access to medical records by clinicians and researchers is currently being tested and evaluated.Discussion: Conversion of non-searchable data into an explorable and computable format will enable clinicians to acquire needed information more conveniently in their clinical care including treatment plan development. Similarly, properly de-identified, complete MRs will serve as a rich source of clinical information to support translational research. Although the method we are developing will initially satisfy the CBCP need for clinical service and research, it will be further developed into a full solution to expand into other disease condition fields. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5123.

Background Each year, approximately 13,110 women under age 40 are diagnosed with breast cancer, with 1,200 dying of the disease. There are approximately 250,000 breast cancer survivors living in the US today who were diagnosed under 40. Compared to older women, young women generally face more aggressive cancers, lower survival rates, and unique psychosocial concerns. Breast cancer in women under 40 is rarely studied. Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. It is a strategic goal of YSC to increase the amount of quality research on young women, to define the greatest research needs for young women with breast cancer, and to advocate these needs to doctors and researchers. In 2001, YSC convened the “Medical Research Symposium on Young Women and Breast Cancer,” consisting of seven researchers from the New York City area from all of the major cancer disciplines. The resulting white paper set an initial YSC agenda on both the current state and future direction for research in young women. In 2012, YSC decided to revisit this agenda, review what progress has been made and what priority research areas remain. Methods In 2012, work on the YSC Research Think Tank (RTT) began. Our goal was to identify the most pressing research questions that would improve the quality and quantity of life for young women diagnosed with breast cancer. YSC assembled doctors, researchers and advocates to focus on six areas of particular importance to its young constituents: risk factors; treatment; metastasis; quality of life; fertility; and pregnancy. Each participant was assigned to a workgroup based on their stated interest and expertise. A young survivor advocate led and coordinated each workgroup. In mid- 2012, these groups met remotely to review the state of the research in each of their assigned areas. They compiled detailed reports summarizing their work and listed the research gaps pertinent to young women. In February, 2013, all RTT participants met in Arlington, Virginia for a two day in-person meeting. Each workgroup briefly presented their work to date and displayed a large poster reflecting what they believed to be the most pressing research questions. During day two of the RTT, attendees rotated through the assigned rooms of three workgroups (other than their own), discussing more fully each of the items that workgroup identified as a research priority. Participants placed each priority on a graph, reflecting how that priority would impact quality and quantity of life for young women. Each workgroup re-assembled and discussed the feedback they received, selecting their top three research priorities. Results Young women with breast cancer remain an understudied population. Taking the knowledge gained and recommendations received at the RTT meeting, YSC is currently drafting a white paper and updated research agenda to be finalized by spring, 2014. These documents will be published and promoted in an effort to focus the research community on the unique issues of young women with breast cancer to extend their quantity and improve their quality of life. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-10-02.

Academic cancer research in the UK is structured around key organizations. The National Cancer Research Institute (NCRI) is a ‘virtual institute’ that brings together government and charitable funders to set priorities and co-ordinate funding of cancer research. NCRI Clinical Studies Groups (CSGs), which provide the site-specific leadership to develop studies, will be adopted into the national portfolio of cancer studies as part of the National Institute for Health Research (NIHR) if the funding is available. The NIHR National Cancer Research Network leads the delivery of research through research networks throughout the UK. Related groups and initiatives facilitate or carry out specific tasks in research development, management and monitoring. Patients have input at all levels and their voice has, throughout the history of NCRI & NCRN, been considered critically important in developing research. The key principles from researchers and clinicians include working together with consumers as partners in the research effort, involving consumers in developing strategy as well as specific initiatives and studies, listening to the consumer voice on research needs and the experience of participating in research, and learning from experience to develop and increase the impact of the consumer role in cancer research. The NCRI Consumer Liaison Group brings together patient and caregiver members to support research development at all levels from the NCRI Board through CSGs to membership of individual Trial and Study Management groups. Impact has been captured in many narratives from researchers, clinicians and patients. Working together in a robust partnership is a particular strength of UK Cancer Research and forms the ideal platform to truly achieve research intended for patient betterment. This is recognized in the recent White Paper: ‘Equity and excellence: Liberating the NHS’. The organization's first decade of patient and public involvement is captured in the NCRI report: Patient, Carer & Public Involvement in Cancer Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-73. doi:10.1158/1538-7445.AM2011-LB-73

Introduction: Advances in technology and internet capability have provided an opportunity for efficient collection of Patient Reported Outcomes (PRO) during medical treatment. Here we describe the development and implementation of a system for monitoring patient reported adverse events (AEs) and quality of life (QoL) using electronic PRO (ePRO) instruments for patients enrolled on the Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis (I-SPY 2 TRIAL), a phase II adaptive platform clinical trial for locally advanced breast cancer. Methods: We designed an ePRO system to increase the accuracy of patient-reported QoL and AE data collection with the intent to act on symptoms in real time. Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY 2 treatment schedule. Weekly surveys contained a maximum of 126 validated, branching logic questions from the Patient Reported Outcomes Measurement Information System (PROMIS®) Health Measures and the National Cancer Institute’s Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE™) instruments. We piloted ePROs at the University of California, San Francisco (UCSF) to evaluate compatibility with a variety of I-SPY 2 patient scenarios (e.g., dose delays). We then staggered rollout of the ePRO system to 22 I-SPY 2 sites to ensure technological feasibility. In order to improve accuracy of data collection, we utilized real-time tracking and developed a Clinical Research Coordinator (CRC) training manual, which integrated workflow diagrams with technical solutions. CRCs were trained using remote video sessions. Results: The UCSF ePRO pilot began in September of 2020. Over 9-months, we accrued 43 I-SPY 2 patients (average age of 43.8 years), whose interactions with the ePRO system informed design improvements. Of the patients who received a baseline ePRO survey, the completion rate was 75.9% (average age of 44.2 years). This represents an increase from the 15-20% baseline completion rate for the 360 UCSF I-SPY 2 patients who received paper-based PRO surveys between May 2012 - January 2019. As of June 2021, the ePRO system was operational at all 22 I-SPY 2 sites. The UCSF pilot revealed that engagement with patients at critical timepoints improved survey completion. CRCs facilitated patient participation by sending instructional emails and communicating with patients weekly. We tracked data completeness using a Patient Tracking report, which displayed each patient’s survey completion history. This real-time tool enabled CRCs to identify patients who had not completed ePRO surveys prior to their visit, so they could be provided a tablet computer to complete the survey in the clinic. After introducing tablets into the workflow at UCSF, patient completion of the baseline survey increased from 75.9% to 80%. Conclusion: The transition from paper to electronic QOL and AE data collection improves the ability of patients to complete PRO surveys, but the process must also be optimized and integrated into clinical workflow and trial conduct. In the future, we will present additional results highlighting the feasibility of multilingual ePRO integration into I-SPY 2. ePRO also provides a new opportunity for data analysis, as well as the potential to reduce high grade toxicity through early intervention. It will allow us to assess QoL and AE data by drug regimen, site, provider, and study treatment. The creation of clinician-facing reports also enables access to patient responses in real-time. By implementing ePRO within I-SPY 2, we not only increase efficiency and accuracy of patient-reported data collection, but also improve quality of care and patient safety. Citation Format: Anna Northrop, Anika Christofferson, Michelle Melisko, Laura Sit, Ebunoluwa Olunuga, Ananya Mittal, Adi Goldman, Thelma Brown, Diane Heditsian, Bev Parker, Susie Brain, Carol Simmons, Alessandra Taboada, Kathryn J Ruddy, Tina Hieken, Mara Piltin, Kiri Cook, Carolina Salvador, Candace Mainor, Anosheh Afghahi, Sarah Tevis, Anne Blaes, Irene Kang, Susan Melin, Laura Esserman, Adam Asare, Dawn L Hershman, Amrita Basu. Improving patient-reported outcome data capture for clinical research: ePRO in ISPY 2, a phase 2 breast cancer study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-02.

The landmark paper by Kane and colleagues was the first report of DNA methylation in the promoter of the human MLH1 gene in sporadic colon cancers with mismatch repair (MMR) deficiency. In both cell lines and primary tumors, promoter methylation was associated with loss of MLH1 protein expression and with a lack of mutations in the MLH1 coding region. Together with subsequent papers that showed that this methylation was directly responsible for loss of MLH1 expression and MMR deficiency, the observation expanded the two-hit hypothesis of tumor suppressor gene loss in cancer to include both genetic and epigenetic mechanisms of gene inactivation. More broadly, the paper contributed to normalization of the hypothesis of an epigenetic basis for cancer development. See related article by Kane and colleagues, Cancer Res 1997;57:808–11

Rationale: Breast cancer diagnosis at a young age is associated with higher risk of recurrence, mortality, morbidity, and impact on quality of life. Long-term effects of treatment may include early menopause, fertility impairment, neuropathy, cardiovascular disease, lowered bone density, and risk of second malignancies. Young women with or at-risk for breast cancer often seek health information through mainstream print and digital media. However, they often find it does not address their unique concerns, is difficult to interpret, or even misleading. Media reports of breast cancer research are often unreliable, misleading, or confusing regarding which information is clinically relevant. Young women with or at-risk for breast cancer, need accurate, clearly presented information based on sound evidence to help them make informed decisions about their specific health needs. To help women better understand media coverage about new research, Facing Our Risk of Cancer Empowered (FORCE) developed the CDC-funded XRAYS (eXamining Relevance of Articles to Young Survivors) program. XRAYS is an online resource that provides brief articles summarizing recent research relevant to young women with or at-risk for breast cancer. XRAYS articles rate the quality and relevance of research, the quality of media reporting, and suggest questions users may be useful to address with health care providers. One critical aim of XRAYS is to improve users’ understanding of the information presented in media reports related to breast cancer. Objective: The objective of this study was to assess whether XRAYS improves readers’ knowledge about information presented in media reports relevant to breast cancer more than reading media reports alone. Methods: To assess XRAYS’ impact on users’ knowledge of information presented in media reports, an evaluator conducted a study with 36 volunteer participants who were attending a FORCE conference. Participants were randomly assigned to treatment or control groups. Both groups completed pre-test paper and pencil multiple choice assessments of knowledge regarding information presented in the article they read, in order to assess baseline knowledge. Then, the treatment group read a media report and the corresponding XRAYS article and the control group read only the media report. After reading the materials, participants answered the same paper and pencil multiple choice questions, so that changes in knowledge could be assessed. Results: A between groups t-test indicated that the groups had comparable baseline knowledge about the material they were assigned to read. A within group comparison showed that the control group’s knowledge did not significantly change between pre- and post-test, while the XRAYS group’s knowledge increased significantly (t(18)=-2.67, p (t(34)=-3.01, p Conclusion: Results indicate that XRAYS is effective in supporting users in learning more factual content from media reports on cancer research than people who read media reports alone, and that it may be useful to develop similar resources to meet other audiences’ needs for information about cancer research. Citation Format: Robin Hilary Pugh Yi, Piri Welcsch, Lisa Rezende, Craig Dearfield, Kelly Owens, Susan J. Friedman. Effectiveness of an online educational resource in increasing lay users' understanding of information in media reports on breast cancer research [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-07.

While rational drug combination design seeks to improve patient outcomes by leveraging biological synergy, outcomes from combination trials often fail. Only 12.4% of phase 1 trials eventually achieve regulatory approval. In vitro evidence has provided the rationale for the drug combinations in 36.6% of phase 1 combination trials, but none of those trials progressed past phase 3 (from a study by Paller CJ et al., 2019). A review of DrugCombDB, a publicly available database of experimental synergy results, supports the idea that such outcomes are mirrored in preclinical data. Analysis of the similarity of synergy scores within indication-specific subsets of cell lines from data in a 2022 paper by Douglass, et al. show that in both breast and lung cancer, combinations predicted to be synergistic in at least one cell line from that indication failed to be synergistic in the majority of indication cell lines more than half of the time. SHEPHERD’s Gene Cluster Voting Algorithm (GCVA) was adapted to improve upon current drug combination design and anticipate transcriptome changes as the result of drug treatment. GCVA relates drug sensitivity to the transcriptome by calculating a list of biomarkers that contribute to sensitivity and resistance for specific drugs, enabling the prediction of drug sensitivity on patient transcriptomic data captured via bulk RNAseq. Via this method, 15,137 publically available synergy data points in the Douglass paper were compared to predictions by our computational approach. For all synergy metrics contained within the dataset (ZIP, Bliss, Loewe, and HSA), the synergistic predictions made by application of GCVA have significantly higher synergy scores compared to the antagonistic predictions made by GCVA (p < .001). These test results support the potential for the application of GCVA to intelligent combination design with the ultimate goal of deployment on a patient-by-patient basis.In addition, analysis of GCVA’s drug efficacy predictions for the cell line DU145 showed that treatment with 9 kinase inhibitors consistently potentiated the predicted efficacy of between 5 and 11 additional drugs. Dasatinib, temsirolimus, and cabozantinib were newly predicted effective after treatment with each and every kinase inhibitor. This data suggests an avenue for the design of intelligent drug combinations based on anticipated transcriptomic changes that may improve on existing synergy prediction methods. Citation Format: Christina Gavazzi, Mikhail G. Grushko, Jeremy M. Goldstein, Mahta Samizadeh, Zakary Y. ElSeht, Katherine Arline. Transcriptome-driven combination design: A computational approach. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4278.

Background Breast conserving surgery with adjuvant radiotherapy (BCS+RT) and mastectomy are currently offered as oncologically equivalent options for the surgical management of early breast cancer based on findings from randomised controlled trials (RCTs) conducted over four decades ago. Since then, locoregional and systemic breast cancer treatments have improved significantly and several recent observational studies suggest a survival advantage in patients receiving BCS+RT compared to those having mastectomy. If BCS+RT is oncologically superior to mastectomy, this may dramatically impact surgical treatment recommendations. The aim of this systematic review was to identify, critically appraise and summarise the contemporary literature comparing survival following BCS+RT and mastectomy to inform surgical decision-making for patients with early breast cancer. Methods A systemic search of MEDLINE, Cochrane Central Register of Controlled Trials and Embase identified studies published between 1st January 2000 to 22nd September 2021. Included were primary research studies published in English comparing overall survival in women undergoing primary surgery with either BCS+RT or mastectomy for unilateral stage I to III breast cancer. Excluded were studies evaluating neoadjuvant chemotherapy; rare breast cancer subtypes (e.g. mucinous) or in specific patient populations (e.g. pregnancy associated breast cancer) and those that completed recruitment before 1st January 1990. We used the ROBINS-I tool to assess the risk of bias in study results and GRADE to assess the overall certainty of evidence. All papers without critical risk of bias were included in a quantitative meta-analysis. Where more than one study reported outcomes in overlapping population-based registry cohorts, the study with the most recent data on the largest cohort was selected for analysis. The primary analysis was a random effects meta-analysis with a fixed effect model undertaken as sensitivity analysis. A secondary meta-analysis was performed for studies only including triple negative breast cancers. All analyses were conducted using STATA17. Results 10,876 abstracts were screened and 157 full-text papers assessed for eligibility, of which 93 (17 multi-centre observational studies, 30 were single-centre observational studies and 46 registry-based studies) met the inclusion criteria for the review. 25 papers were excluded from meta-analysis due to an overall critical risk of confounder bias and 27 were excluded due overlapping study populations. 36 studies (34 with serious risk of bias and 2 with moderate risk of bias) reporting survival outcomes on 1,321,291 patients (729,789 undergoing BCS+RT and 591,502 undergoing mastectomy) were included in the meta-analysis. The pooled hazard ratio was 0.72 (95% CI 0.64– 0.81, p< 0.001, I2 97.6%) demonstrating improved overall survival for patients undergoing BCS+RT compared with those receiving mastectomy. The sensitivity analysis, using a fixed effect model, showed a hazard ratio of 0.88 (95% CI 0.87 – 0.89, p< 0.001, I2 97.6%) for survival in women undergoing BCS+RT compared with mastectomy. Meta-analysis of 8 studies reporting survival in 17,181 patients with triple negative breast cancer showed a hazard ratio of 0.73 (95% CI 0.68 – 0.79), p< 0.001, I2 34.7%) for those receiving BCS+RT versus mastectomy. Discussion This meta-analysis provides further, albeit very low certainty evidence, that overall survival is improved following BCS+RT compared with mastectomy in a contemporary cohort of patients treated for early-stage breast cancer. These results should be interpreted with caution due to the heterogeneity of included studies and the high risk of bias associated with observational data. As future RCTs will not be feasible, well-designed large-scale prospective observational studies are needed to provide better evidence to support surgical decision-making in early-stage breast cancer. Citation Format: Kiran Kasper Rajan, Katherine Fairhurst, Beth Birkbeck, Rebecca Wilson, Jelena savovic, Chris Holcombe, Shelley Potter. PD15-04 Overall survival following breast conserving surgery and adjuvant radiotherapy compared with mastectomy for early stage breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-04.

Objective: The aim of this study was to conduct a bibliometric and visual analysis of breast reconstruction related research at China and abroad published in the past five years, to understand the research status and development trend in this field, to discuss the focus of research in different countries and different disciplines, and to provide reference for other researchers. Methods: Relevant literatures about breast reconstruction were retrieved from the Web of Science Core Collection. The VOS viewer 1.6.15 software was used to extract the authors, countries, institutions and keywords to generate network maps of high-yield authors, institutions and high-frequency keywords clustering network. Results: 4,815 documents meeting the requirements were retrieved, which showed an upward trend in the past five years. Regarding the discipline, 838 documents (17.40%) were published by breast surgery and Cancer Surgery, 3308 (68.70%) were published by plastic surgery, and 669 (13.90%) were jointly published by both types of researchers. A total of 161 clinical trials were registered in the US clinical trial registry (ClinicalTrial.gov), of which intervention trials accounted for the highest proportion (107, 66.46%), followed by observational trials (54, 33.54%) and patient registry (4, 2.48%). Regarding country distribution, the United States conducted the largest number of breast reconstruction-related clinical trials (45, 27.95%), followed by China (22, 13.66%), Italy (12, 7.45%), France (11, 6.83%), the Netherlands (9, 5.59%). The top ten institutions contributed 983 articles (20.41%), and the institution with the highest number of publications was MD Anderson Cancer Center (144, 2.99%), followed by Harvard Medical School (139, 2.89%), Sloan-Kettering Cancer Center (125, 2.60%), Stanford University (113, 2.35%) and University of Michigan (102, 2.12%). The author with the largest number of documents was Bernard T. Lee of Beth Israel Deaconess Medical Center (BIDMC), with 56 papers and 540 citations. The most cited author was Andrea L. Pusic of Brigham and Women’s Hospital, with 48 papers and 1,332 citations. Chinese authors published 310 documents, accounting for 6.44%. There were differences in the disciplines of the main authors between China and abroad. In China, authors from breast surgery published a larger proportion of documents (138, 44.52%), while the number of documents published by authors of plastic surgery (129, 44.52%) and the joint publication of both types of authors (43, 13.87%) was relatively small. However, foreign documents mainly came from authors of plastic surgery (74.74%). There were more cooperative groups (155) formed by major foreign authors, and joint publishing between groups was more frequent; while Chinese author formed only 16 cooperative groups with less cooperation. Keyword cluster analysis showed that top five keywords were flap, implant, breast cancer, immediate breast reconstruction, tissue. In breast surgery publications, top five keywords were breast cancer, breast reconstruction, complications, implant, immediate breast reconstruction, while in plastic surgery publications top five keywords were flap, implant, tissue, breast cancer, infection. Authors from breast surgery focus more on oncology-related issues in breast reconstruction, while in plastic surgery, more attentions were paid on autologous tissue reconstruction. Conclusion: Breast reconstruction had gradually attracted the attention of Chinese and foreign researchers. Compared with foreign countries, there were problems such as lack of high-quality research and less cooperative research in China. There were differences in the research focus of breast reconstruction between China and abroad, which is mainly related to the differences in the disciplines of researchers. Citation Format: Hengyu Ren, Shuang Hao, Jiajian Chen, Zhimin Shao, guangyu liu, A-Yong Cao, Jiong Wu. Current Status and Focus of Breast Reconstruction Research in China and Abroad-A Bibliometric Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-56.

Introduction Due to improvements in breast cancer (BC) diagnostics and treatment, the population of BC survivors is growing. BC treatments may have adverse effects that lead to an increased risk of developing type 2 diabetes mellitus (T2D). It is therefore important to investigate the risk of T2D in patients with BC in general and according to type of adjuvant BC treatment. Objectives To conduct a systematic review and meta-analysis investigating the association between early BC and the risk of subsequent T2D diagnosis. A secondary aim was to examine this association according to type of adjuvant BC treatment––chemotherapy and endocrine therapy (ET). Methods We searched PubMed and Embase using variations of the search terms breast cancer (population), ET, tamoxifen, aromatase inhibitors (AIs) and chemotherapy (exposures), and diabetes mellitus (outcome). Two authors screened papers for eligibility by title and abstract using Covidence and reviewed full texts of eligible papers. Guided by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist, study data were extracted. Using random-effects models, we calculated relative risks (RRs) and associated 95% confidence intervals (CIs) for the association between BC, adjuvant BC treatment (ET overall, tamoxifen, and AIs), and subsequent T2D. We used funnel plots to assess publication bias in the analyses. Results Among 16 eligible studies, 11 reported on T2D risk after BC, chemotherapy, or ET; five studies investigated more than one association. Compared with patients without BC, those with BC had elevated risk of T2D overall (RR=1.27, 95%CI=1.15-1.41), particularly those who received any ET (RR=1.23, 95% CI=1.16-1.32). Among BC patients only, risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (RR=1.19, 95% CI=1.13-1.25). Due to few studies, analyses investigating T2D risk after treatment with AIs and chemotherapy were inconclusive. Conclusion Our findings support an association between BC and subsequently elevated risk of T2D, particularly after tamoxifen use. Further research is needed to determine the impact of ET overall, AIs and chemotherapy on the incidence of T2D in patients with early BC. Funding This project was funded from the following source: The Novo Nordisk Foundation (NNF20OC0065928) Citation Format: Nanna Jordt, Kasper Kjærgaard, Signe Borgquist, Reimar W. Thomsen, Deirdre Cronin-Fenton. Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A systematic review and Meta-Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-23.

Introduction Patients referred for genetic counseling do not consistently complete a family history questionnaires (FHQ), which is required before scheduling a genetic counseling appointment (GCA). A paper survey has traditionally been used to collect this FHQ data. This requires the genetic counselor to manually input the patient's FHQ information into a pedigree generator prior to scheduling their GCA, thereby delaying the genetic screening process. Some genetic counseling centers have switched from using this paper survey to a web-based pedigree-generator, like PROGENY, for collecting patient's FHQ data. No literature to date has evaluated the impact of this change on patient compliance with completing the required FHQ, the genetic screening process, or patient outcomes. This study assesses changes in patient compliance and genetic screening efficiency with the implementation of PROGENY compared to traditional surveying as a means of collecting FHQ data. Hypothesis More patients will complete the FHQ and GCA and there will be reduced time between patient referral and completion of the FHQ and GCA with the use of PROGENY compared to the traditional paper survey. Methods This is a retrospective chart review of patients referred for genetic counseling six months before and after implementation of PROGENY. Independent t-tests assuming unequal variances were conducted using JMP to compare genetic screening efficiency with and without the use of PROGENY. Results This study found that 41% more patients completed the FHQ and 25% more patients completed a GCA when using PROGENY. Further, there was a statistically significant reduction in the time between referral and completion of the FHQ (t(311)=9.14, p Conclusions These results support our hypothesis and suggest that utilizing PROGENY in collecting patient FHQ data correlates with improved patient compliance and genetic screening efficiency. Future work should investigate how quality improvement such as this impacts patient outcomes, such as the timeliness of finding an actionable genetic mutation and detecting cancerous and precancerous lesions. Some limitations of this study include high variability. This is likely due to factors such as appointment cancellations, geneticist availability and workload, and patient age, ethnicity, gender, and socioeconomic status. Future work should assess the impact of these factors on variables such as patient compliance and efficiency of the genetic screening process. Citation Format: Hennick TM, Khan T, Moroose R, Bisson R. Improved patient compliance and genetic screening efficiency following implementation of an electronic pedigree survey (PROGENY) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-20.

Background: Almost a quarter of older adults in the United States will identify themselves as Hispanic/Latino by 2060. Our group has previously developed and validated a self-administered geriatric assessment tool which can be used to identify functional, psychological, social and cognitive impairments among older patients with various types of cancer. Among English-speaking older adults, completing this tool using paper/pencil or a tablet takes a median of 15-21 minutes (min), with < 10% needing assistance to answer it (Hurria, JOP 2016). However, the utilization of this tool among Spanish-speaking older adults has not been tested. We assessed the feasibility of administering a translated and validated Spanish version of our geriatric assessment tool for older Hispanic women with breast cancer, and identified their preferred format (tablet or paper/pencil). Methods: Spanish-speaking women aged ≥ 65 years with a diagnosis of breast cancer completed the geriatric assessment twice on the same day. Patients were randomized into 3 groups: paper/pencil twice; tablet and paper/pencil in random order; and tablet twice. We assessed the proportion of patients requiring assistance to complete the geriatric assessment, the time needed to complete it, and the proportion of patients who thought the geriatric assessment was difficult/very difficult. Results: 140 older women with breast cancer completed the geriatric assessment twice and were evaluable. Mean age was 71.6 years (SD 5.8), 53% had ≤ 8th grade education, 43% were married, 45% were retired, 32% were homemakers, and 6% were employed. The participants came from 13 different Spanish-speaking countries, although 70% were born in Mexico. For 90%, Spanish was their primary language, and 75% spoke only in Spanish at home. Regarding computer skills, 64% of the patients said they had none. 39% (n = 54) were unable to complete the geriatric assessment on their own; mean time to complete the geriatric assessment was 29 min (range 8-90); and 28% (n = 39) thought the geriatric assessment was difficult/very difficult. The most common reasons for needing assistance were difficulty understanding questions (39%) and visual problems (31%). Patients with ≤ 8th grade education took longer to complete the geriatric assessment (mean 37.2 vs 29.4 min, p < 0.01), and more often needed help completing the assessment (51% vs 19%, p < 0.01) than those with ≥9th grade education. 53% of the participants preferred using a tablet to answer the geriatric assessment, while 47% preferred paper/pencil. Conclusions: A substantial proportion of Spanish-speaking older women with breast cancer required assistance to complete our self-administered geriatric assessment tool. This may be a consequence of the low educational level we found among this patient population. Tailoring assessments for diverse populations with particular attention to educational level is needed in multicultural settings. Citation Format: Soto-Perez-de-Celis E, Vazquez J, Kim H, Sun C-L, Somlo G, Yuan Y, Waisman JR, Mortimer JE, Kruper L, Taylor L, Patel NH, Moreno J, Charles K, Roberts E, Uranga C, Levi A, Katheria V, Paredero-Perez I, Mitani D, Hurria A. A self-administered geriatric assessment tool for Spanish-speaking older women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-16-04.

Purpose: Collecting patient reported outcome (PRO) data in a systematic way enables an objective evaluation of treatments and its related outcomes. By using the disease specific questionnaires developed by the International Consortium of Health Outcome Measurement (ICHOM) this allows for comparison between physicians, hospitals and even different countries. Methods In November 2016 we implemented a web-based system to collect PRO data at the breast center at Charité University hospital using the ICHOM data set. All new patients who are seen at the breast center are enrolled and are answering a predefined set of questions using a tablet computer. Once they start their treatment at Charité automated emails are sent to the patient at predefined treatment points. Those emails contain a web-based link through which they can access their questionnaires. Results Until now we have enrolled 834 patients and initiated 2470 questionnaires. 9.44% of patients were under 40 years of age, 49.7% between 40 and 60, 39.6% between 60-80 and 1.3% over the age of 80 years. The average return rate of questionnaires is 72% without any additional intervention. When asked about preference regarding paper versus online 7.9% of the patients 50 to 60 years of age would prefer paper, 18% in the 60-70 years of age group and 21.2 % in the age group over 70 years. Conclusion Measuring PRO in breast cancer patients in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate. Citation Format: Karsten MM, Speiser D, Hartmann C, Lippold K, Kirchberger V, Blohmer J-U. First implementation of the International Consortium of Health Outcomes Measurement standard for breast cancer at a major German university hospital using a web-based tool to measure patient reported outcomes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-05.

Tumorigenesis begins with cells that have normal mutation rates. As the cells become immortal and accumulate different numbers of mutations along the way, current literature splits in two describing if and how mutation rates increase as the cancer progresses. Some argue that as the mutation rates are small (mutation rate in healthy cells is per nucleotide site per cell division) and malignant cells are loaded with thousands of different types of mutations, they must have acquired a mutator phenotype early in their development. Others argue that immortality of malignant cells, and their rate of proliferation is responsible for their genetic instability and number of mutations observed in their genome. We conduct a review of the literature with the key words “mutation rate” and “cancer” in their title. We review 123 papers and found that description of mutation rates varied in the published work. This leads to estimates of mutation rates in cancer from per nucleotide site per cell division. Some of this variation in mutational rates arises across different organs of the body, for instance liver cells have a higher mutation rate than heart and brain. Cancer treatments such as chemotherapy influence mutation rate, and mutation rate of drug and multidrug resistance cancer cell is higher than newly diagnosed cancer cells. Further, mutation rate is defined differently in different literature, some papers measure the mutation rate in a population or a gene, some calculate it per base pair, genome, or mitosis. Here we provide a comprehensive picture of published mutation rates across different cancer types in order to inform cancer models and treatment plans for individual patients. We propose a unified framework for discussing and reporting mutation rate of cancer cells and formulations on how to switch between definitions. Citation Format: Fargam Neinavaie, Andrew Kramer. Does mutation rate of cancer cells change as the stage of the disease advances? [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A038.

Introduction Especially in oncology patients, Patient Reported Outcomes (PRO) play an increasingly important role to measure subjectively perceived health status and treatment effects. At the moment, paper-based surveys of PRO still predominate (pPRO); in recent years, data on patient-relevant endpoints is being increasingly collected electronically (ePRO). The aim of the study was to analyze the acceptance of an ePRO-survey tool in breast cancer patients within the PRAEGNANT multicenter trial. Furthermore, it should be considered, whether differences in response behavior between pPRO and ePRO can be identified (reliability check). Materials and Methods ePROCOM (Patient Reported Outcomes and Compliance Anaysis) was conceptualized as a monocenter, randomized, parallel-group, cross-over study. Female patients with diagnosis breast cancer aged more than 18 years were included.We randomized the patients into one of two study arms. In study arm A the patients are first asked to use the electronic, web-based tool to document the patient questionnaire (EORTC QLQ C-30 and FACT-B). Afterwards the patients were asked to fill and evaluate the paper-based questionnaires accordingly, followed by evaluation of usability, acceptance and capability. In study arm B the course varies by meaning that paper-based evaluation will be followed by the assessment of electronic data capture. Results N=110 patients with breast cancer in adjuvant or neoadjuvant situation completing the study during an outpatient visit at the University Hospitals in Tuebingen and the National Cancer Centre Heidelberg (average age: 52.4). In most patients, there were no differences in terms of acceptance between pPRO and ePRO. Only in some older patients with a lower quality of life hurdles for ePRO could be identified, because of lower acceptance rates. We could not find significant differences in response behavior between pPRO and ePRO. Discussion Because no differences in response behavior could be identified, the tool can be define as reliable possibility to measure patient reported outcomes. E-PRO surveys appear to be suitable for use in breast cancer patients. However, there is a need of support in older and more ill patients, to participate form the technical capabilities of ePRO. Citation Format: Wallwiener M, Simoes E, Hartkopf AD, Taran F-A, Keilmann L, Sickenberger N, Stevanovic S, Belleville E, Ladra C, Schneeweiss A, Wallwiener D, Brucker SY, Graf J. Reliability and acceptance of e-based survey instruments for measuring patient reported outcomes (PRO) in breast cancer patients: First results of the ePROCOM study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-11-05.

Introduction Over the last 2 decades, an increasing number of primary breast cancer (PBC) patients opted for a risk reducing contralateral mastectomy, to minimize risk of subsequent contralateral breast cancer (CBC). Therefore, accurate risk estimates of CBC are important for patient tailored counseling and decision making regarding treatment. Currently, CBC risk estimates are determined by BRCA1/2 mutation status, age at PBC diagnosis and family history. For other risk factors, results are inconclusive. We therefore aimed to quantify the association with CBC risk for patient, tumor and treatment related factors as reported in the literature. Methods Medline was searched for publications on CBC risk by one reviewer (DA). We focused on associations between CBC risk and BRCA1/2 and CHEK2*1100delC mutations, SNPs, risk-reducing salpingo-oophorectomy and various factors at PBC diagnosis: family history of breast cancer (BC), age, BMI, menopausal status, mammographic density, TNM-stage, receptor status, morphology, administered radiotherapy and adjuvant systemic treatment. Eligible papers were published in English between 01-01-1990 and 01-04-2015, investigated female patients with invasive early BC and reported relative risk (RR) estimates (i.e., hazard ratios, relative risks or odds ratios). We combined RR estimates using a random effects model. Heterogeneity was assessed using the I2 statistic. Forest plots for crude and adjusted estimates were generated stratifying for mutation status (i.e., BRCA1, BRCA2, CHEK2*1100delC), non-carriers and unselected patients (i.e., population/hospital based cohorts). Results After screening of 1,423 papers for title and abstract, 173 eligible papers were fully read, and 96 papers fulfilled the inclusion criteria. Both in the unselected group and in the BRCA1 and BRCA2 groups, administration of adjuvant endocrine therapy (vs. not), was associated with decreased CBC risk (RR, 0.62 (95% CI 0.55-0.69), 0.55 (95% CI 0.39-0.77), and 0.62 (95% CI 0.40-0.95), respectively). Adjuvant chemotherapy was associated with reduced CBC risk in unselected patients (RR 0.73; 95% CI 0.62-0.86). CBC risk was increased in unselected patients who received radiotherapy at age30 (vs. For CHEK2*1100delC mutation carriers and non-carriers, information on factors affecting CBC risk was scarce. In non-carriers, the RR for adjuvant chemotherapy was 0.60 (95% CI 0.53-0.68). Conclusions In unselected patients, adjuvant systemic treatment for PBC decreases CBC risk while a lobular morphology of PBC, high BMI, and a family history of BC increase the risk of CBC. Data is scarce for carriers of a BRCA1/2 or CHEK2*1100delC mutation and non-carriers. This review identifies prognostic factors to consider for individualized CBC risk estimation which may support medical decision making in BC patients. Citation Format: Akdeniz D, Schmidt MK, McCool D, van den Broek AJ, Hauptmann M, Seynaeve CM, Steyerberg EW, Hooning MJ. Risk of metachronous contralateral breast cancer: Systematic review and meta-analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-05.

The SUM breast cancer cell lines were developed in the 1990s and since that time, one or more of these cell lines have been distributed to over 500 laboratories world-wide. As a result, there are currently nearly 4000 papers in the peer-reviewed literature that contain data obtained with one or more of these cell lines. In addition, over the years, our laboratory and others have developed a number of complex genomic data sets for these cell lines, most of which are unavailable to the research community. The genomic data that have been developed for the SUM lines include: copy number/gene amplification data, gene expression profiling data using multiple platforms, whole exome sequencing data with cancer specific point mutation data, proteomic profiling data, and most recently, genome-scale shRNA screening data for each of the lines. The shRNA screening data functionalizes the other genomic data sets, adding significant power to these analyses. To make these genomic data sets available to the research community, we developed the SUM Breast Cancer Cell Line Knowledge Base (www.sumlineknowledgebase.com). This web-based resource provides information about each cell line, such as information on the patient from which the line was derived, a narrative summary of each cell line with a focus on the genomic drivers that are important for each line, a bibliography of published papers using each cell line and much more. To make the genomic data accessible to all breast cancer researchers, we have developed a number of data mining tools that allow researchers to rapidly and easily identify the key functional genes and pathways operative for each cell line. The tools developed so far include: a series of KEGG Pathway Engines, an Oncogene Signature tool, a Gene Query tool, a Proteomics tool and a Functional Druggable Signature tool. The KEGG Pathway Engines allows users to map shRNA screen data or gene expression data onto any KEGG pathway for any cell line and rank order pathways based on essentialness and druggability. The Oncogene Signature tool identifies all genes in each line that are genomically altered in each line, the status of each of those genes in the shRNA screen, and the druggability of each potential oncogene. The Gene Query tool allows researchers to search for any gene and obtain data on the status of that gene in any of the cell lines. The tool also generates a rank-ordered list of the cell lines based on the essentialness of the gene in each cell line., and provides data on copy number, expression level, hit status in the shRNA screen and the potential druggability of each gene. Thus, this SUM Breast Cancer Cell Line Knowledge Base and the tools contained within this web-based resource, allow researchers using any of the SUM lines to rapidly probe the deep biology of any cell line, identify the driving genomic alterations, most important KEGG pathways, and the most effective drug strategies for each cell line line. Work currently in progress is aimed at expanding this Knowledge Base to include all breast cancer cell lines, which will make this resource useful to all breast cancer researchers who use cell lines in their work. Citation Format: Stephen Paul Ethier, Kathryn Duchinsky, Daniel Couch. The SUM breast cancer cell line knowledge base (SLKBase): A knowledge base and functional genomics platform for breast cancer cell lines [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-13.

Background: Despite increasing utilization of patient-derived xenografts (PDXs) in early drug development, there are no agreed upon metrics for assessment of PDX growth inhibition for agents given alone or in combination. In the present study, we aim to investigate what metrics are being used in the literature, as well as among the National Cancer Institute PDX Development and Trial Centers Research Network (PDXNet) investigators. Methods: Relevant PDX literature was identified and retrieved using an information retrieval tool, RetriLite, to search for articles that met following criteria: 1) Published between 01/2018 through 12/2019; 2) Published in a journal with impact factor of 10 or above; 3) Search terms included: Cancer, PDX(s), patient derived xenograft(s), and patient-derived xenograft(s). Exclusion criteria included: 1) Brain tumors; 2) Immune-oncology/non-solid tumors; 3) Studies with no detailed information; 4) studies from PDXNet investigators. In addition, a questionnaire regarding PDX analysis practices was distributed to NCI PDXNet investigators and responses were analyzed. Results: Sixty-five studies with relevant information were included in this systematic literature review and 15 NCI PDXNet PIs from all six centers responded to the survey representing the general practice in the network. The most commonly used tumor growth assessment metric was comparisons in tumor volumes in different treatment arms, used by 33 (51%) of 65 PDX papers and 13 (87%) of 15 PDXNet investigators. Thirteen different growth metrics were reported in the PDX literature and ten different metrics were used by PDXNet investigators. PDXNet investigators were more likely to use growth metrics analogous to clinical endpoints compared to the PDX literature, including percent change of tumor volume (80% vs 17%), event-free survival (EFS: 40% vs 11%), and overall survival (33% vs 8%). PDXNet investigators were also more likely to assess objective response rate (ORR) compared to the PDX literature (60% vs 12%); several different cutoffs were used for defining response and progression. For combination therapy, most investigators and literature compared tumor volumes across treatment arms, with few looking at measures of synergy or dynamic effects and with variable utilization of other metrics such as OR and EFS. In PDX literature, of the 40 papers with combination therapies presented, at least one monotherapy control arm was missing in 7 (18%), and four (10%) only compared growth with the no treatment control arm. Conclusions: In summary, there is great variability in growth metrics used in the PDX community. To better use PDXs as preclinical models and increase the reproducibility of treatment effect on PDXs, a joint effort is needed to harmonize approaches in PDX growth assessment. Citation Format: Dali Li, Min Jin Ha, Yvonne A. Evrard, Huiqin Chen, Lisa M. McShane, Jeffrey Grover, Jing Wang, Bingliang Fang, Timothy DiPeri, Michael T. Lewis, Lawrence Rubinstein, Jack A. Roth, Jeffrey H. Chuang, James H. Doroshow, Jeffrey A. Moscow, Funda Meric-Bernstam. A systematic review of the tumor growth metrics of patient-derived xenograft (PDX) models in the literature and in NCI PDXNet centers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3009.

PubMed is the most widely used database and search-engine in biomedical and healthcare field. It has evolved more powerfully using Best Match algorithm. However, users still have several difficulties to ‘catch' their target papers in limited time, which fundamentally originates from the conventional two-dimensional ‘top-down' display method of search results. We conducted a survey for 76 medical experts (including oncologists, surgeons, gastroenterologists, psychiatrists, et al) about their behaviors and difficulties in using PubMed. The most common ‘unmet needs' of users were (1) the rank of citation counts or impact factors, (2) more three-dimensional and interactive display of search results, and (3) author rank and network. Reflecting the results above, we developed a novel PubMed visualizing program, EEEvis version 1.0 (medical and healthcare evidence visualizer), and launched it on www.EEEvis.com. The basic operating principle of EEEvis version 1.0 is to visualize the metadata of PubMed and PubTator (a web-based text mining-tool) using (1) advanced filter tools, (2) a scatter & box plot using citation counts over years, (3) an author map reflecting the ranks and networks, and (4) a reinforced search list (Table 1). All the data crawling is based on the API (application programming interface) of PubMed and PubTator. To computing and visualizing the crawled metadata, we constructed two servers; a hidden station server and an open UI (user interface) server. In the interim result of our ongoing pilot study in searching oncology-related literatures, the two quantitative factors including (1) time to ‘catch' the target paper and (2) success rate finding the required paper showed significant improvement. Other qualitative factors including (3) user convenience, (4) interactivity, and (5) willingness to use EEEvis next time showed good results. Now we are developing EEEvis version 2.0 using text-mining technology and applying multiple patents for this program. Comparison between EEEvis and PubMedProgramsEEEvisPubMedFilter sectionBy article typeYesYesBy publication yearYesYesBy citation count of paperYesNoBy impact factor of journalYesNoInteraction section using Brushing & Linking techniqueScatter plot of citation counts by yearYesNo(with box plot of citation counts by year)YesNoMap of author networkYesNoList sectionSort by best matchYesYesSort by most recentYesYesSort by citation countYesNoSort by author or journalNoYesCitation count of each paperYesNoImpact factor of each journalYesNoPubTator informationYesNoData crawlingHow to crawl results from Pubmed serverIndirect using APIDirectLimit of result numbers10,000 (best matched)NoneUser experience in searching cancer-related keywords in pilot study (ongoing)Time to display results after entering keywordsNot inferiorPromptTime from visualizing results to finding the required paperSuperior(= faster)InferiorSuccess rate of finding the required paper after visualizing the resultsSuperiorInferior Citation Format: Jong-chan Lee, Brian J. Lee, Hyunjoo Song, Changhee Park, Chan-Young Ock, Yuna Youn, Hyojae Sung, Sungjin Woo, Jaihwan Kim, Jin-Hyeok Hwang. A novel PubMed visualizer using human-computer interaction technology: EEEvis.com [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 248.

Introduction: The use of 3D models to study pancreatic ductal adenocarcinoma (PDAC) has evolved in the last years. There are several described models all of which may seem to be equally relevant. However, which of these methodologies is preferred in pancreatic cancer research has not been clarified. There is no head-to-head comparison described so far and no data to prove which may better reflect the full spectrum of a patient's tumor and exhibit disease stage-specific characteristics. Our hypothesis is that if a model is useful it should be adopted and therefore referenced in the literature. Although there may be some concerns to this approach, we tried to show the most referenced models of 3D cultures in PDAC by different methodologies. Material and Methods: We performed a PubMed search using the following mesh terms ‘pancreatic ductal organoids', ‘human pancreatic ductal cancer organoids', ‘mouse pancreatic ductal cancer organoids' and ‘pancreatic ductal cancer organoids'. Using PubMed and Web Of Science we analyzed the citation network with regards to number of citations, impact factor and where in the article was the reference included. If it was included in the material and methods section, we confirmed they used that model for the article and not for other reasons. In that way, we tried to define the use of the model based on published literature. We defined this as the MM references. Results: According to our mesh terms, we identified 4 organoid models: Skala (Pancreas, July 2016), Muthuswamy (Nature, November 2015), Kuo (Nature, July 2014) and Tuveson (Cell, January 2015). They were cited 1062 times from the date of publication to October 5, 2020. Skala's methodology had the lowest number of citations (43), while Kuo ranked third (161), followed by Muthuswamy (217) and Tuveson (641). While examining the citation network of each model, we excluded reviews and book chapters and found that Skala's citations included 19 articles, Kuo's 62, Muthuswamy's 101 and Tuveson's 348. After analyzing the MM references we found that Skala's methodology had 5, Kuo's 8, Muthuswamy's 6 and Tuveson's had 79. We then identified the papers in which the authors were part of the original contributors for the purpose of identifying how extended the use of the method was. Taking this into consideration, Skala accounted for 1 out of 5 MM references (16.7% ), Kuo for 7 out of 8 (87.5%), Muthuswamy for 2 out of 6 (33.3%) and Tuveson for 58 out of 79 (73.4%). One caveat from our work is that not every published paper includes the original methodological reference in their publication and, if that is the case, it will not be reflected in our data. Conclusion: Tuveson's methodology is widely adopted, not only by the Tuveson Lab but also by the rest of the PDAC research community. Citation Format: Mariano Ponz-Sarvise, Carmen de Carvajal. 3D systems to study pancreatic ductal adenocarcinoma (PDAC). Comparison of the most referenced models using a bibliometric approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2979.

Background: The Avon Breast Health Outreach Program (BHOP) supports community-based organizations to provide breast cancer education and outreach, and navigate low income and uninsured women to breast cancer screening and treatment. BHOP organizations collect demographic and health information on clients through a standardized interview using the Clinical Intake Form (CIF). Research demonstrates that transitioning away from paper completion to audio-computer assisted self-interview allows for increased rates of survey completion. Given the advancement of tablet technology, there is significant opportunity for organizations to adopt electronic data collection of clinical information to improve data quality. Objective: This presentation compares rates of CIF completion collected among a low income, diverse client population via two modalities; self-administered paper-based interviews (SAPI) versus electronic collection using iPads. Methods: The CIF is organized into three sections: demographics [12 items], breast health [9 items], and access/use of health services [5 items]. In 2013, 26 BHOP grantees adopted and utilized iPads to administer the CIF with the iSurvey application, after receiving training and technical assistance on tablet usage. Data were restricted to women >=18 years, who self-administered the CIF, English-only, collected between March and December 2013, and among only those grantees who employed both modalities. The BHOP dataset was analyzed to compare CIF completeness across the two modalities. ‘Completeness’ is defined as having a response to every question in the CIF; ‘missing’ is defined as any question that was not responded to or was left blank. Percent of completeness and mean number of missing responses in the CIF overall and by section were analyzed by modality. Odds Ratios (OR) on completeness by modality were also calculated controlling for race, income, education, place of birth and residence. Results: There were 8,004 CIFs analyzed; 2,144 via iPad (27%) and 5,860 via SAPI (73%). Among the iPad mode, 84% of the CIFs had complete data, compared to 47% in the SAPI. The mean number of missing values across the entire CIF was 0.2 via iPad, compared to 1.3 with the SAPI. SAPI variables had ten or more times as much missing data as the iPad variables (e.g., "self-reported breast symptoms" item had 7% missing data in SAPI vs. 1% in iPad). Adjusting for key demographic characteristics, clients were seven times more likely to complete the entire CIF via the iPad as compared to the SAPI [Overall OR= 7.3(6.0-9.0)]. Conclusions: Given the significantly higher rates of CIF completion using iPads, there are important implications for health care organizations to adopt and utilize electronic collection of their health interview data. Future research should study iPads ability to handle high patient volume in less time and with more accuracy compared to SAPI. Discussion: Tablets are a relatively inexpensive option for organizations dedicated to assuring complete data collection. While administrative barriers arise with new technology, the significantly positive aspects of tablet data collection of increased quality and completeness overshadow such burdens. Citation Format: Lindsay Senter, Marvin R Aliaga, Kelly M Opdyke, Kathryn Gates-Ferris, Marc Hurlbert. Improving completeness of client-level data collection in the Avon Breast Health Outreach Program through electronic tablet technology [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-01.

Background: Patients treated for early stage breast cancer (BC) have a 30% lifetime risk of developing metastatic disease. Numerous studies have demonstrated that dormant bone marrow disseminated tumor cells (DTCs) are independently associated with risk of recurrence and death, yet interventions targeting these cells are lacking. The PENN-SURMOUNT (Surveillance Markers of Utility for Recurrence after (Neo)adjuvant Therapy) Screening Study was launched in 2016 to screen high risk BC survivors for DTCs using bone marrow aspirate (BMA) and identify eligible DTC positive patients for clinical trials. Given the novelty of this approach, we concurrently developed and pilot tested a PRO measurement strategy to study how the screening method of BMA and disclosure of DTC results impacts early-stage BC patients. Methods: PENN-SURMOUNT is a single center prospective, longitudinal cohort study examining BM and blood biomarkers of MRD among patients within 5 years of BC diagnosis who have high risk criteria (positive axillary nodes, triple negative biology, ER+ with Oncotype Dx ≥ 25 and/or high risk Mammaprint, or pathologic residual disease after neoadjuvant chemotherapy). From May 2019 – August 2021, we recruited patients on SURMOUNT to complete PRO surveys at baseline (T0), after BMA (T1), and after disclosure of DTC results (T2). Surveys were administered in paper form initially, then electronic form starting Feb 2021. PRO survey instruments were selected through literature review, followed by consensus among multidisciplinary clinical and research experts and patient advocates. PRO measures assess recurrence distress (Quality of Life in Adult Cancer Survivors, QLACS), illness intrusiveness (Illness Intrusiveness Ratings Scale, IIRS), and decision making (Decision Regret Scale). Additional survey items assess tolerability of the BMA and patients’ risk perception and cognitive understanding after DTC results disclosure. Descriptive statistics summarize PRO survey compliance and responses at T0, T1, and T2 in the total population and the population who reported longitudinal data for T2. Results: 61 of 66 eligible patients on the SURMOUNT trial enrolled in the PRO pilot study and completed a baseline survey, of which 47 (77%) tested negative for DTCs. Mean completion rates were 0.92 at T0, 0.85 at T1, and 0.56 at T2. After electronic survey implementation, completion rates increased to 0.94 (T0), 0.97 (T1) and 0.81 (T2). At T0, 36 (59%) patients reported a high risk perception of developing BC recurrence at 5 years and 42 (69%) during their lifetime. Mean T0 recurrence distress using the QLACS subscale was 14.6 (SD 6.3) out of possible score 4-28, compared to an expected mean of 11.42 (SD 5.48) in a general survivorship population. Mean T0 illness intrusiveness was 27.3 (SD 13.9) out of possible score 13-91. At T1, approximately 85% of patients agreed that they correctly understood the purpose of the bone marrow procedure and what the procedure would entail. 44 (72%) of patients reported a maximum pain score Citation Format: Tara Kaufmann, Patrick Chang, Shoshana Rosenberg, Elizabeth Frank, Brian Hobbs, Lauren J. Bayne, Isoris Nivar, Brooke L. Goodspeed, Killian M. Rohn, Emily M. Kugler, Kevin Fox, Susan Domchek, Angela Bradbury, Payal Shah, Hayley Knollman, Rachel C. Jankowitz, Igor Makhlin, Amy S. Clark, Lewis A. Chodosh, Angela DeMichele, Katherine Goodfellow. Pilot study of a patient-reported outcome (PRO) measurement strategy to determine impact of screening for minimal residual disease (MRD) in high-risk breast cancer survivors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-01.

Patient reported outcome (PRO) measures can be collected in clinical trials or clinical care through questionnaires. PROs allow a direct measure of how a patient is feeling and functioning, directly from the patient without interpretation by another person or clinician. PROs give patients a voice. Although there are challenges to collecting PROs, these challenges can be overcome. When deciding which measures to collect there are some things to keep in mind. For example, if the questions are relevant and meaningful to what the patient is experiencing they will be more likely to fill them out, providing useful information. The questionnaires can also be given in multiple formats (electronic, paper, telephone) to accommodate the preferences of different patients. However, collecting PROs is not enough, the information collected needs to be used to inform future patients or inform patient care. Additional challenges and benefits of collecting PROs in breast cancer research and clinical care from the patient perspective will be discussed. Citation Format: Patty Spears. Patient Advocate Perspective [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED1-4.

Purpose/Objective(s): The purpose of this paper is to report the dosimetric effects of conscious sparing of contralateral lobe of thyroid gland in carcinoma breast patient receiving locoregional radiation by tangential beam Intensity Modulated radiotherapy technique. Materials/Methods: Treatment plans of 20 Ca Breast patients, who received post mastectomy adjuvant locoregional radiotherapy, were evaluated. Since October 2021 we adopted a department protocol of conscious sparing of contralateral thyroid in breast radiotherapy. 10 of these had conscious sparing of contralateral thyroid (group A) whereas 10 of old plans were evaluated when C/L thyroid were not given constraints & are being passively spared due to location on contralateral/non treatment side of neck (group B). Treatment planning was done using tangential beam (6 MV) IMRT in Eclipse 13.7 TPS in all of these patients. All of these patients received treatment to chest wall & SCF. RTOG contouring guidelines were followed in all the patients. Prescription Dose was 40Gy in 15# for both groups. The best treatment plans were selected ensuring 95% PTV dose coverage and acceptable dose to OARs. Uniform contouring, plan optimization & evaluation protocols were followed for all of these patients. Results: The mean thyroid volume in group A is 4.30cc & in group B is 3.99cc which is not statistically different (P value -0.639) The mean dose of thyroid in group A is 7.98Gy whereas in group B it is 17.00Gy which is spastically significant (P value – 0.000003). Comparison of mean dose to contralateral lobe (in Gy) between the two groups Groups No. Mean ± SD ‘t’ value P value Thyroid dose with constraint 10 7.98±1.46 -6.702, df=18 0.000003* Thyroid dose without constraint 10 17.00±3.99 Unpaired ‘t’ test applied. P value = 0.000003, Significant Conclusion: OARs present on contralateral side are passively spared due to the location. This often results in a tendency of not actively prescribing constraints to these. This study emphasizes that conscious sparing of contralateral Thyroid lobe can further reduce the dose to significant levels. This reduction can preserve thyroid function further. Further clinical trials are required to corroborate this dosimetric gain with clinical thyroid function preservation. Citation Format: Manish Chomal, Minaal Iyer, Ananth Kalimurthy, Joshua Sahay, Sushanta Banik. Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-15.

Background: Numerous studies have documented the relative advantages that computer assisted self-interview (CASI) technology holds over traditional interviewing methods in collecting research data on stigmatized and/or risky health behaviors. However, few studies have explored the broader implications of using CASI to collect basic client-level data during routine health promotion and disease prevention screenings. Aims: The present study aims to address this gap in research by comparing the quality of client-level data collected via audio-computer assisted self-interview (ACASI) with data collected via face-to-face and self-administered paper-based interviews among a sample of clients served through the Avon Breast Health Outreach Program (Avon BHOP). Methods: A total of 303 clients served through the Avon BHOP were sampled from three U.S. sites between November 2011 and March 2012. Clients were randomly assigned to complete the Avon BHOP client intake form (CIF) via one of three interview modes: face-to-face interview (FFI), self-administered paper-based interview (SAPI), or ACASI. We conducted logistic regression and determined odds ratios with 95% confidence intervals to test our hypothesis that use of ACASI would result in significantly higher rates of CIF completion than either FFI or SAPI. We compared rates of completion of the entire CIF, as well as completion of each of the three CIF sections: Demographics, Breast Health Information, and Correlates of Breast Health. Results: Clients were significantly more likely to complete the entire CIF via ACASI than either FFI or SAPI interview modes. The greatest differences were observed when comparing rates of completion between ACASI and SAPI, as clients were almost five times more likely to complete the CIF via ACASI as opposed to SAPI (OR = 4.7, p < 0.001). Additionally, when comparing rates of completion of the three CIF sections on Demographics, Breast Health Information (e.g. mammogram history), and Correlates of Breast Health (e.g., smoking behavior, alcohol consumption), we found that clients were between 3.2 and 7.2 times more likely to complete the sections via ACASI as opposed to SAPI. Discussion: Overall, we found that use of ACASI resulted in significantly higher rates of overall form completion and lower rates of missing data than use of SAPI or FFI, with the greatest identified disparity in form completion between ACASI and SAPI. This study has important implications for breast health specialists or any health practitioners who regularly rely on self-administered questionnaires and/or face-to-face interviews to collect important health information. We recommend that where feasible, ACASI be utilized as an effective means of collecting high quality client-level data. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-02.

Large volumes of data have been generated in biomedical field every day and made publicly accessible. A significant portion of the data are highly under-analyzed. On the other hands, biomedical researchers having problems that can be solved by these data do not have the expertise to access and analyze the data. The BioKDE (Biomedical Knowledge Discovery Engine) platform aims to bridge this gap by accelerating biomedical discovery through integration and mining of large volumes of public genomic data. We have integrated a large volume of genomics data from TCGA (the Cancer Genome Atlas) and GEO (Gene Expression Omnibus) database, which are linked with patient clinical information. Powerful and versatile query functions were built for the integrated data. Basic and advanced analysis tools have been implemented with user-friendly interfaces. Pipelines can be built by chaining the query tools with analysis tools to perform sophisticated data acquisition and analysis tasks very conveniently. Pipelines can be saved and shared among researchers to quickly replicate certain analyses using the same dataset or different datasets. A large number of novel discoveries have been made, which can be used directly to write scientific research papers using these discoveries alone or by combining with additional experimental validation studies. We will present a few case studies published recently to illustrate the power of the BioKDE. We are looking for collaborators to write papers together for the discoveries we made. The platform can be accessed at http://www.insilicom.com. Citation Format: Xiaodong Pang, Mayassa J. Bou-Dargham, Yuhang Liu, Zihan Cui, Linlin Sha, Tingting Zhao, Jinfeng Zhang. Accelerating cancer research using big data with BioKDE platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2247.

Background: Interval cancers (IC) are cancers that are discovered within the interval between two screening examinations, i.e. they present themselves clinically before the next scheduled screening examination. A mammography screening programme that is run in a population with a high breast cancer incidence can have a high interval cancer rate, and still have as protective an effect as a screening programme with a low IC-rate run in a population with a low breast cancer incidence. The effectiveness of a mammography screening programme is therefore normally evaluated by comparing the IC-rate to the expected breast cancer incidence without screening, i.e. the proportional interval cancer rate. The expected breast cancer incidence in absence of screening, or background incidence is, however, difficult to approximate, as the introduction of a screening program makes it difficult or impossible to find a comparable population group that is not screened. We propose to use a new measure, the number of interval cancers out of the total number of cancers, called the interval cancer ratio, as an alternative measure for the burden of interval cancers in an organized mammography screening programme. We seek to validate this new measure by comparing it to the old measure, the proportional interval cancer rate. Method: We did a systematic review and included studies: 1) covering a service screening programme, 2) with inclusion of women aged 50-69 years, 3) that contained observed data, papers based on modeling only were excluded, 4) that contained data on number of interval cancers and number of women screened, or on interval cancers rate, and 5) that contained information on estimated breast cancer incidence rate of the background population. This resulted in 6 papers describing 12 mammography screening programmes. Results: The IC- ratio in studies including only initial screens, varied from 0.13 to 0.32 while the proportional interval cancer rate varied from 0.24 to 0.55 in the same studies. In studies including only subsequent screens the IC-ratio varied from 0.21 to 0.47 with a proportional interval cancer rate of 0.26 to 0.67. One study with mixed initial and subsequent screens with a majority of initial screens had an IC-ratio of 0.18, whereas the proportional interval cancer rate was 0.33. In the study with a majority of subsequent screens had an IC-ratio was 0.32 and the proportional interval cancer rate was 0.67. There is a strong linear relationship between the interval cancer ratio and the proportional interval cancer rate in initial screens. In subsequent screens the trend is linear but is less obvious. Conclusion: Our main aim with this study was to propose and validate the interval cancer ratio as an alternative measure for the burden of interval cancers. The new measure seems to capture the burden of interval cancers just as well or better than the old measure, without the need for increasingly difficult estimations of background incidence, which makes it a more accessible tool when evaluating mammography screening programme performance. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-04-03.

Background The Avon Breast Health Outreach Program (BHOP) supports community-based organizations to conduct education and outreach to link low-income and uninsured women to routine breast cancer screening. These organizations capture health and demographic information for clients screened as a result of outreach using a standardized Client Intake Form (CIF). Prior research demonstrated higher rates of overall form completion for data collected via audio-computer assisted self-interview (ACASI) versus face-to-face or self-administered paper interview. Advances in tablet computer technology provide additional options and potential advantages for collecting client-level data electronically. Objective To determine if electronic CIF data collection via tablet is a practical alternative to paper-based data collection, and assess the relative administrative burden, advantages and disadvantages for Avon BHOP-funded organizations for each method. Methods English and Spanish copies of the CIF were created in iSurvey, an application developed for iPad. Currently funded grantees (n = 101) were invited to apply for the pilot; 34 of 38 applicants in 24 states were selected, with priority given to organizations with a majority of English- or Spanish-speaking clients, and greater annual client volume. Pilot sites received a tablet pre-loaded with iSurvey. Grantees received web-based training and individual technical assistance on tablet use, data collection and submission procedures. Avon BHOP staff conducted telephone follow-up to assess organizations’ feedback concerning acceptability to program staff and clients of CIF data collection using the tablet, and effects on data quality and administrative processes relative to paper CIFs. Quality assurance was conducted on all CIFs submitted via iSurvey to identify duplicate or invalid records. Results 948 CIFs (838 English, 110 Spanish) were submitted using the tablets during a two month period from March 21 to May 21, 2013. Five organizations submitted fewer than 5 CIFs, eight did not submit any CIFs, and three organizations discontinued participation; their tablets were reassigned to different organizations. Grantees using the tablets for CIF data collection found the program easy to use and data entry efficient. Challenges reported included difficulties integrating the tablets into clinic flow, lack of familiarity with tablet technology among clients and staff, and an inability to review data for errors or completeness prior to electronic submission. Conclusion CIF data collection via tablet is an option for electronic data capture for some organizations. However, many organizations reported challenges in effectively integrating this new technology into existing clinic flow and administrative processes. Discussion While tablets are a relatively inexpensive and practical option for electronic client data collection in some settings, some organizations reported a preference for paper forms. Many of the identified administrative barriers may be resolved through the provision of technical assistance and capacity building support to grantee organizations. Future analysis may focus on the completeness of data collected via tablet versus paper. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-08-15.

Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and persistence of long-term toxicities. Methods: CANTO (NCT01993498) is a French prospective clinical cohort study of 10 150 patients with stage I-III BC from 26 cancer centers. Patients matching all CANTO inclusion and exclusion criteria, who received RT and were still in follow up, in the 10 top recruiting CANTO centers, with a minimum follow up of 3 years, were selected for CANTO-RT. Eligible patients had breast/chest wall +/- lymph node RT with curative intent. Individual full DICOM RT files (CT, RT Structure, RT Dose, RT Plan) were collected, anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform using AQUILAB Share Place™ and Analytics Dose module. Characteristics of the patients and tumors (including TNM, histology, HER2, estrogen and progesterone receptor) were recorded at baseline. Characteristics of the treatments, skin, lung, cardiovascular, neurological, musculoskeletal toxicities (CTCAE v4.0), QOL (BR23, QLQC30), cosmetic, and oncological outcomes were assessed at diagnosis (baseline), 3-6 (M0), 12 (M12), 36 (M36) and 60 (M60) months after completion of primary surgery, chemotherapy or radiotherapy whichever came last together, with blood, plasma and serum tests. Results: CANTO-RT enrolled 3875 BC patients between June 2012 and February 2017 with a median follow-up of 64 months :1947 (50.2%) left side, 1850 (47.8%) right side and 78 (2%) bilateral BC. The vast majority of patients had hormone receptor-positive tumors 3321 (85.7%) and 553 (14.3%) had human epidermal growth factor 2 (HER2) positive tumors; 2586 (66.7%) had stage pT1 and 2525 (65.2%) pN0 disease; 2087 (53.8%) neoadjuvant or adjuvant chemotherapy, 477 (12.3%) adjuvant trastuzumab and 3138 (81%) adjuvant endocrine therapy. Among 3797 patients with unilateral RT, 3065 (80.4%) had breast conserving surgery, 747 (19.6%) total mastectomy; 2712 (71.5%) sentinel node and 1080 (28.5%) axillary dissection. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%) including internal mammary chain in 844 patients (21.8%). Most patients 3691 (95.3%) were treated with 3D conformal RT and 184 (4.7%) with intensity-modulated RT. Normofractionated RT (2Gy/fraction) was mostly used (69.9%). Clinical target (breast, chest wall, lymph nodes) and contoured organs at risk (heart, left anterior descending coronary, lung, spinal cord, esophagus, thyroid, brachial plexus, contralateral breast, humeral head) contours and dose/volume histograms were automatically extracted after quality control procedure excluding corrupted files and inconsistencies 36 (1%) (Table 1). Conclusion: CANTO-RT is the largest early breast cancer prospective cohort with full individual clinical and DICOM RT data available. CANTO-RT is a valuable resource, open for collaborative projects, for identification and validation of clinical and dosimetric predictive factors of RT related toxicities. Further long term follow up is ongoing. Table 1.Baseline characteristics of the CANTO RT breast cancer patients.CharacteristicsBreast Cancer Patients [N(%) or Mean (range)]Age at enrolmentMean (range), years56.5 (23.3-85.8)Tumour size (pT)T037 (1)T12586 (66.7)T21058 (27.3)T3177 (4.6)Missing17 (0.4)Nodal status (pN)02525 (65.2)11035 (26.7)2223 (5.8)379 (2)Missing13 (0.3)Tumour histologyInfiltrating Ductal3011 (77.7)Lobular473 (12.2)Others (including mixed)381 (9.8)Missing10 (0.3)Hormone Receptors positiveNegative541 (14)Positive3321 (85.7)Missing13 (0.3)HER2Negative3305 (85.3)Positive553 (14.3)Missing17 (0.4)Type of chemotherapyNo chemotherapy1788 (46.1)Neoadjuvant chemotherapy450 (11.6)Adjuvant chemotherapy1629 (42)Peri-adjuvant chemotherapy (neo + adjuvant)8 (0.2)Hormonal therapyNo730 (18.8)Yes3138 (81)Missing7 (0.2)Herceptin treatmentNo or Not applicable3378 (87.2)Yes477 (12.3)Missing20 (0.5)Type of breast surgerylumpectomy3113 (80.3)Mastectomy734 (18.9)Right lumpectomy and Left mastectomy13 (0.3)Right mastectomy and Left lumpectomy9 (0.2)None6 (0.2)Type of lymph node surgerySentinel node2746 (70.9)Axillary dissection1086 (28)Right sentinel node, Left axillary dissection20 (0.5)Right axillary dissection, left sentinel node12 (0.3)None11 (0.3)Radiation therapyRight Side1850 (47.8)Left Side1947 (50.2)Bilateral78 (2.0)Patients with boostNo or Not applicable1217 (31.4)Yes2658 (68.6)Lymph node levels treatedNone2519 (65)Yes1356 (35)Level 1284 (20.9)Level 2340 (25.1)Level 31072 (79.1)Level 41348 (99.4)Internal mammary chain844 (62.2)Irradiation techniques3D3691 (95.3)IMRT184 (4.7)Fractionation regimensNormofractionation 25-fractions2707 (69.9)Hypofractionation 15-16 fractions166 (4.3)Hypofractionation and Partial breast irradiation51 (1.3)Unspecified fractionation - CTV breast or chest wall not delineated951 (24.5) Citation Format: Thomas Sarrade, Rodrigue Allodji, Youssef Ghannam, Guillaume Auzac, Sibille Everhard, Ophélie Querel, Youlia Kirova, Karine Peignaux, Philippe Guilbert, Claire Charra-Brunaud, Julien Blanchecotte, Rezart Belshi, David Pasquier, Séverine Racadot, Céline Bourgier, Sandrine Ducornet, David Gibon, Fabrice André, Florent De Vathaire, Sofia Rivera. CANTO RT: The largest prospective multicenter cohort of early breast cancer patients treated with radiotherapy including full DICOM RT data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-01.

Glypican-3 (GPC3) is a cell-surface glycoprotein that is frequently overexpressed in hepatocellular carcinoma. GPC3 undergoes extensive post-translational modification including cleavage and glycosylation. This review focuses on the structure and function of GPC3 in liver cancer, highlighting the post-translation modification (PTM) of the tertiary and quaternary structures of GPC3 as a potential oncogenic regulatory mechanism. We propose that the function of GPC3 in normal development can vary with extensive PTM and that dysregulation of these processes leads to disease. Defining the regulatory impact of these modifications can provide a deeper understanding of the role of GPC3 in oncogenesis, epithelial-mesenchymal transition, and drug development. Through review of current literature, this paper provides a unique perspective on the role of GPC3 in liver cancer, focusing on potential regulatory mechanisms of post-translational modifications on GPC3 function at the molecular, cellular, and disease level.

Introduction. Fifty years has passed since the publication of Austin Bradford Hill’s classic paper on causal inference. Much has changed in the biomedical and public health sciences regarding cancer causation during that half century, but Hill’s considerations (often called “criteria”) remain durable. That said, there is a curious phenomenon involving Hill’s seminal work that has escaped the attention of the scientific community. His consideration of analogy—the last on his list just after experimentation—has all but disappeared. The purpose of this paper is to rethink and resurrect analogy as an important consideration in causal inference in environmental epidemiology. Methods. Given that this is a conceptual—non-quantitative—project, the methods used are the informal logic of scientific thinking, methods of systematic reviews, and judgment. Results. In contemporary epidemiology, analogy is either completely ignored (e.g. in many textbooks), equated with biologic plausibility or coherence, or aligned with the scientist’s imagination. None of these examples, however, capture Hill’s description of analogy which emphasizes the contrast of two bodies of evidence. Coupled with developments in the methods of systematic assessments of evidence—including but not limited to meta-analysis—analogy can be restructured as a key component of causal inference. For theoretical support see similar methods in biomedical ethics and artificial intelligence. Practical examples will be discussed. Conclusions. Analogical reasoning—an updated version of analogy—can emerge assuming the following developments: (1) a collection—a library—of known cases of causal inference (i.e. bodies of evidence involving established causal relationships), including, for example, the assessments of the International Agency for Research on Cancer (IARC) and the National Toxicology Program (NTP), (2) a systematic process for describing the key features of a causal relationship creating paradigm cases, and (3) an objective comparison of a “new” body of evidence for a putative causal relationship with a relevant paradigm case. Citation Format: Douglas L. Weed. Cancer causation: rethinking the role of analogy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5301. doi:10.1158/1538-7445.AM2017-5301

Introduction: Approximately 5-10% of pancreatic cancer diagnoses are associated with inherited cancer syndromes and family cancer history assessment is a critical component of identifying these high risk families. We developed and validated a comprehensive web-based family history survey, which collects cancer type and age of diagnosis for first and second degree relatives directly from patients, generating a summary and cancer risk model scores for medical care teams in real-time. We tested feasibility and performance of this tool in an outpatient pancreatic cancer clinic setting. Methods: 161 patients age 18 years and older, with appointments at the University of Michigan Multidisciplinary Pancreatic Tumor Clinic between September 2015 and February 2016 were approached during their clinic visit to complete the web-based survey on an iPad device. Responses were compared to the clinic’s current family history collection method with medical assistants entering data from paper forms into the electronic medical record (EMR) during the intake process. Data completeness, and proportion of patients identified as meeting criteria for genetic referral were compared between the two survey modalities. Results: 92.5% of patients approached agreed to take the iPad survey. Time to complete the survey ranged from 2-50 minutes (mean 12 minutes). Patient ages ranged from 24 to 87 years, with a median age of 64. Patients who were unfamiliar with the iPad technology and/or had difficulty recalling ages of diagnoses of relatives accounted for a greater amount of time taken to complete the survey. Only 6.0% of patients were unable to complete the survey prior to the end of their visit. Of the 128 patients that completed the iPad survey, 82 (64.1%) had a personal history of pancreatic cancer; the remaining 46 (35.9%) presented with a personal or family history suggestive of increased pancreatic cancer risk. Based on clinical criteria for genetic referral for known inherited syndromes related to increased pancreatic cancer risk, we determined that 53.7% of patients with a pancreatic cancer diagnosis met criteria for genetic counseling by iPad survey vs 41.4% by the paper form. Of patients without a pancreatic cancer diagnosis, 23.9% met genetic referral criteria using the iPad tool vs 21.7% using the paper form. Among patients with pancreatic cancer, the most common reasons for meeting high risk criteria were having another family member with pancreatic cancer (12.2%) or having two or more relatives on the same side of the family with cancers associated with increased pancreatic cancer risk (e.g., breast, ovarian, melanoma; 17.1%). Among those without a personal history of pancreatic cancer, the most common reasons for meeting high risk criteria were family history of ovarian cancer (6.5%), and having three or more related family members with the aforementioned cancers (13.0%). Conclusions: Assessment of family history using a web-based tool is feasible, as demonstrated by high participation and completion rates among all age groups. Both iPad and paper surveys identified a significant percentage of patients for genetic referral. Improvements in obtainment of cancer relevant family history and better inclusion of such data in the EMR may play an important role in better screening of high risk individuals for pancreatic and other types of hereditable cancers. Citation Format: Kara Anne Schradle, Heather Gail Cameron, Riya Kumar, Erika Koeppe, Elana Leflein, Cristina Moisa, Matthew Demerath, Elena Martinez Stoffel, Diane M. Simeone.{Authors}. Assessment of family cancer history in a pancreatic cancer clinic: A pilot study of a web-based survey. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A11.

Exosomes are nanovesicles produced by cells embedded of cellular information and represent a formidable natural cargo for communication. The name “FedExosomes” denotes the general idea that exosomes could deliver cargo that conveniently manipulated could be of help for patient therapy. Up to now, a few papers demonstrated that modified exosomes could deliver drugs specifically to cancer cells and many laboratories are now studying their properties and compositions. Differently from previously published papers that focused on the efficacy of the doxorubicin encapsulated in exosomes (exoDOX), for the first time, we demonstrated that unmodified exosomes loaded with DOX are less toxic than free DOX by altering the biodistribution of the drug. The heart tissue of mice treated with a toxic dosage of DOX exhibited scattered cytoplasmic paranuclear vacuoles and focal intense eosinophilic cytoplasm, devoid of their transversal striations with moderate disarrangement of cardiomyocytes. The heart tissue of exoDOX treated mice at the same dosage appeared normal. Mass spectrometry studies confirmed that although the quantity of exoDOX in the blood was the same compared to DOX, accumulation in the heart was reduced of about forty percent. Maximum tolerated dose of exoDOX treated mice is double than free DOX. Mice treated at double concentration of exoDOX vs DOX have reduced tumor burden compared to free DOX without observable toxicity. We demonstrated that exoDOX increased the therapeutic index of DOX by reducing toxic side effects and envisage a similar mechanism for others chemotherapeutic drugs. Since the exosomes could be prepared directly from the patients, our preclinical approach could have a possible immediately application in the clinic. Citation Format: Flavio Rizzolio, Mohamad Hadla, Giuseppe Corona, Isabella Caligiuri, Stefano Palazzolo, Sabrina Semeraro, Amelia Gamini, Vincenzo Canzonieri, Giuseppe Toffoli. Exosomal encapsulation of doxorubicin reduces the cardiac toxicity of mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2205.

Cancer treatment is increasingly guided by molecular analyses designed to identify clinically actionable genomic alterations in individual patients. The discovery of BRAF mutations in human cancer, and the subsequent development and FDA authorization of selective BRAF inhibitors highlight the potential clinical impact and current limitations of precision oncology paradigms. In 2002, Brose and colleagues reported that the distribution of BRAF mutations differed in melanoma and lung cancer and that not all BRAF mutations were functionally equivalent. Here, we discuss this landmark paper, which foreshadowed subsequent research elucidating how biochemical differences among mutant alleles within the same gene and lineage-specific differences among cancer types impact drug sensitivity. Such translational studies provided a road map for the development of novel RAF inhibitors and rational combination strategies that promise greater clinical activity and/or more favorable toxicity profiles. See related article by Brose and colleagues, Cancer Res 2002;62:6997–7000

Introduction: Given the recent advances in early detection, improving access to care and the introduction of more effective anti-cancer medications including endocrine therapy, targeted and immunotherapy, more women with breast cancer survive their disease. Majority of patients with breast cancer express hormone receptors (estrogen and or progesterone receptors) on cancer cells. Aromatase inhibitors (AI) are the gold standard treatment of hormone-sensitive postmenopausal women with breast cancer. Several studies had documented the accelerated bone loss associated with AI. The use of bone modifying agents like bisphosphonates and denosumab had resulted in significant improvement in bone mineral density among females treated with AI. In this paper, we study the efficacy of implementing a comprehensive program on bone health for such patients. Patients and Methods: Postmenopausal women with hormone-sensitive early-stage breast cancer treated with endocrine therapy (ET) were included. A comprehensive bone health program was implemented. The program includes extensive counselling by medical oncologist, calcium and vitamin-D supplements, increase milk intake and exercise. Patients with baseline lumbar spine or total hip T-scores ≥ -2 were given short intravenous bisphosphonate infusion every 6 months. Patients with osteoporosis are referred to and followed in a specially designed “osteoporosis clinic”. Results: Between 2013 and 2019, a total of 210 patients fulfilled the eligibility criteria and were enrolled. All were female, median (range) age 67 (43-86) years. All patients had a pathologically confirmed diagnosis of breast cancer, treated and followed up at our institution. High risk patients (n=103, 49.0%) were treated with 6-8 cycles of chemotherapy, including anthracyclines and taxanes. Following the completion of chemotherapy, all patients were treated with endocrine therapy. Patients with low-risk disease (n=107, 51.0%) were treated with upfront endocrine therapy-alone. Aromatase inhibitors, letrozole or anastrozole, were the endocrine therapy of choice in all patients. At baseline, and prior to start of AI, the median T-scores at the hip and lumber spines were -1.0 (range: -3.6, 1.9) and -1.4 (range: -3.9, 2.6), respectively. Osteoporosis was documented in 38 (18.1%) patients while 101 (48.1%) others had osteopenia; none were on any treatment or even aware of their BMD. 46 (25.3%) patients had vitamin-D deficiency while 74 (40.7%) others had vitamin-D insufficiency and none were on prior active replacement therapy or even aware of this problem. Following at least 12-months of endocrine therapy, 32 (84.2%) of patients with osteoporosis and 69 (68.3%) of those with osteopenia had a stable or higher BMD. Thus, the number of patients with osteoporosis declined to 27, 12.9% of the total cohort. On the other hand, 41 (57.7%) of those with normal baseline BMD had a drop in their follow up BMD. Vertebral fractures, presented with back pain and documented by imaging studies, were reported in 3 (11.1%) patients with osteoporosis compared to none in patients with normal BMD, p=0.021. Rib fracture and hip fracture were reported in one patient each and both had normal BMD before and after AI therapy. Conclusions: Postmenopausal women with breast cancer are at risk of osteopenia and osteoporosis. Such risk increases significantly with the use of AI. However, early interventions with modifiable risk factors, Vitamin-D supplements and use of bone-modifying agents can lower this risk. Citation Format: Razan Mansour, Ula Al-Rasheed, Akram Al-Ibraheem, Shereen Abu Jaradeh, Rashid Abdel-Razeq, Rayan Bater, Noor Mashahdani, Shrouq Tbayshat, Hikmat Abdel-Razeq. The efficacy of a comprehensive bone health program in maintaining bone mineral density in postmenopausal women with early-stage breast cancer treated with endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-30.

Background: It is estimated that 12.7% of the US population had been prescribed an antidepressant in the past month and that women are twice as likely to be on an antidepressant than men. Therefore, it is especially important to understand how SSRIs interact with female hormones and influence risk and progression of female cancers, especially breast cancer, being the most common. Up to a third of women use selective serotonin reuptake inhibitors (SSRIs) after breast cancer diagnosis. Recent investigation has demonstrated serotonin receptor (5-HTR2B) expression in the breast and identified serotonin production in breast tumor cells as an indicator of poor prognosis. This paper presents a unique comparative assessment between the influence of prior SSRI use, continuous and after use relative to breast cancer diagnosis on overall mortality among breast cancer patients. This analysis is expected to provide a clearer understanding of the influence of SSRIs based on period of use relative to time of diagnosis on overall mortality. Methods: The present study includes a population-based sample of consecutively diagnosed breast cancer cases identified as part of the Breast Cancer in Northern Israel study. Patients were recruited and followed from January 1st, 2000 to July, 2019. Participants completed risk factor questionnaires regarding medical, reproductive, family and personal history of cancer, medication use and health habits. Additionally full prescription data was available through the Israeli national CLALIT medical database. An analysis of 5976 newly diagnosed women with breast cancer was performed. K-M survival analysis and time-dependent and time-independent COX proportional hazard models were performed to determine overall survival based on interval of SSRI use. Results: Use of SSRIs in the 5 years prior to breast cancer diagnosis was associated with a 66% increase in overall mortality (HRadj.=1.66; CI: 1.05-2.63). Use of SSRIs with use that initiated after breast cancer diagnosis was associated with an 81% increase in mortality (HRadj.=1.81; CI: 1.58-2.06). Use of SSRIs in the 5 years post-diagnosis was associated with a significant (P5 years). For 24 months of SSRI use after diagnosis, there was a 99% increase in mortality (HR=1.99; CI: 1.39-2.83). Conclusion: SSRIs used both prior to and after breast cancer diagnosis are associated with reduced overall survival in breast cancer patients. The effect of SSRIs on mortality persisted even after adjustment for tamoxifen and factors thought to mediate the relationship behind depression and increased mortality including increased age at diagnosis, comorbidities and stage at diagnosis pointing toward other mechanisms mediating the association between SSRIs and impaired survival in breast cancer patients. Additional research is needed to better understand who is susceptible to the adverse effects of SSRIs on breast cancer overall mortality. Treating depressive symptomatology is of high importance. The results presented here indicate that risks and benefits of SSRI use after breast cancer diagnosis should be weighed when initiating pharmachotherapy and additional research is needed to better understand why SSRIs are associated with worse outcomes in breast cancer patients. Citation Format: Avital Fischer, Hedy Rennert, Ofra Barnett, Gad Rennert. The impact of SSRI use on overall survival in breast cancer patients in northern Israel [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-51.

Background: The COVID-19 pandemic is negatively affecting patient enrollment, therapy administration, and patient visits in breast cancer clinical trials worldwide. COVID-19 may have a lasting impact on how clinical trials are conducted, and guidelines are necessary to inform trial design and patient safety. While many groups and journals have recently published guidelines, including NCCN, ESMO, IQVIA, and Lancet Oncology, there is no consensus on how to treat patients in the current environment. Understanding and quantifying the impact of the pandemic on clinical study sites will help inform the rational development of a consensus approach. The goal of this survey was to gather site-level data on the impact of COVID-19 from clinical sites participating in the POLARIS study (NCT03280303), an ongoing, prospective, real-world, noninterventional study in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer receiving palbociclib plus endocrine therapy. Methods: Two rounds of questionnaires were sent to investigators at POLARIS study sites: 1 via email March 26-27, 2020, and 1 via telephone from April 30-May 20, 2020. The questions on COVID-19 impact and management are shown in the Table. Results: Eighty of 122 POLARIS study sites contacted responded to the March questionnaire, and 86 responded to the April-May questionnaire. In March, 33% (26/80) of the surveyed population were working predominantly remotely, 26% (21/80) were working both onsite and remotely, and 31% (25/80) were working onsite. Approximately 24% of sites reported delayed data entry. The option of telemedicine or office visits was offered to subjects at approximately 73% (58/80) of sites, and 11% (9/80) of sites were restricted to telemedicine visits. In April-May, 36% (31/86) of respondents reported an impact on study management and 64% (55/86) reported no impact. Approximately 94% (81/86) of surveyed sites felt they were able to maintain clinical studies despite the challenges due to COVID-19, and 79% (68/86) of sites had the option for telemedicine and/or office visits, while 18% (16/86) had no telemedicine alternative. In April-May, 38% of sites reported an impact on patient visits. Conclusion: Although these findings must be interpreted with caution due to the limitations of survey studies, the results suggest that approximately 1/3 of the study sites will experience an impact on their responsiveness to correspondence, timely data entry, and subject management due to the COVID-19 pandemic. Telemedicine may be used to mitigate the effect of the pandemic on clinical trial execution. Pfizer (NCT03280303) Table. Survey QuestionsMarch Questionnaire (March 26-27, 2020)QuestionResponsesWorking onsite or remotely?26 sites are predominately working remotely21 sites are working a combination of onsite and remotely25 sites are working onsite7 sites provided inconclusive responsesSubject visits in office, by phone, by video, or a combination of 3 options?50 sites are using a combination of onsite and telemedicine8 sites have onsite visits9 sites have telemedicine visits only8 sites provided inconclusive responses4 instances where question was inapplicable due to no active subjectsIs data entry delayed?19 sites responded Yes54 sites responded No6 sites provided inconclusive responsesIs collection of biomarker blood samples impacted?11 sites indicated there will be impact to biomarker collection28 sites indicated there will be no impact to biomarker collection40 instances where question was inapplicable due to no subjects participating in collectionWhat other study areas are impacted?20 sites indicated impact due to financial challenges or limited abilities while working remotelyRemaining sites did not note any additional areas of impactPatient-reported outcome questionnaire issues?Most sites had not experienced any issues, but an overwhelming majority inquired about the ability to do them via phone or mail. Many sites and subjects expressed preference for the paper questionnaire instead of the electronic version.May Questionnaire (April 30-May 20, 2020)QuestionResponsesHas COVID-19 impacted your site’s ability to execute a study?55 sites responded No• Clarify impact on your site31 sites responded Yes• Subject visits impacted (limited onsite visits): 24• Institutional restrictions/limited staff: 7Is there any impact on scheduled onsite standard of care patient visits?53 sites responded No33 sites responded YesPlease indicate which if any of the following apply to your site:67 sites responded that telemedicine is in place for subject visitsProcess in place for remote patient study visits16 sites responded that there is no alternative for telemedicineProcess is used for remote patient study visits1 site noted that they have no active subjectsAlternative methods are available to deliver drug1 site noted that subjects are attending on site visitsOther1 site did not respond to questionHow able are you to maintain ongoing studies at this time?27 sites are extremely able to do so42 sites are very able to do soExtremely able to do so12 sites are moderately able to do soVery able to do so5 sites are able to do so only a littleModerately able to do so• COVID impact is felt more profoundly at 4 sitesA little able to do so• Financial barrier has limited one site’s time on studyNot at all able to do so0 Sites unable to do so at all Citation Format: Debu Tripathy, Joanne L Blum, Gabrielle Rocque, J. Daniel Cuevas, Jennifer Specht, Steven Corso, Jawad E Francis, Stephanie Mendez, Veneta Pope, Joseph Cappelleri, Yao Wang. Impact of COVID-19 on study sites: Survey analysis from the noninterventional POLARIS study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS2-10.

Background: Family history is one of the strongest predisposing factors for male breast cancer (MBC). Several MBC susceptibility genes have been identified, but the risk of MBC for individuals with a pathogenic variant in these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes. Methods: A search query was developed to identify MBC-related abstracts indexed in PubMed, with the followings structure: "Breast Neoplasms, Male"[Mesh] OR (((“Men”[MESH]) OR (male*[TIAB]) OR (man[TIAB]) OR (men[TIAB])) AND ((“Breast Neoplasms”[MESH]) OR (Breast Cancer*[TIAB]) OR (Breast neoplasm*[TIAB]))). A validated natural language processing (NLP) method was applied to retrieve and classify abstracts reporting penetrance estimates. Abstracts labeled as relevant were manually reviewed. The full-text papers of identified penetrance studies were then annotated to extract MBC risk data. These penetrance studies’ bibliographies were also reviewed to ensure comprehensiveness. Results: We identified 17 penetrance studies from 11,799 abstracts, covering five MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2 (Table 1). 53% of these studies were case-control studies, while the rest were cohort studies. Odds ratio (OR), cumulative risk (CR), and relative risk (RR) were three commonly reported risk measures. For BRCA2, eight out of nine studies reported significantly increased risk of MBC or a lifetime CR of over 6%; only one study reported an increased but not statistically significant risk. For BRCA1, one out of six studies reported an elevated lifetime CR of 5.8%, while a second reported a minor increase (OR=1.49) that was statistically significant. The risks reported in the remaining four studies showed no statistically significant increase in risk. Seven studies reported the penetrance of CHEK2, but the risks diverge between the variants tested (Table 2). All three PALB2 studies reported significantly increased risk, while only one ATM study reported an increased risk of MBC, which did not reach statistical significance. Conclusion: To our knowledge, this review provides the first complete set of reported penetrance data for five MBC susceptibility genes. Contradictory MBC risks (significantly increased risk vs. risks that were not statistically significant) were common, which may be due to the studies’ different ascertainment criteria resulting in risk estimates for differing populations. Risk across these studies cannot be directly compared unless studies adjust for ascertainment, though this cataloging of risk defines our current understanding. Table 1: MBC penetrance studiesGeneNumber of StudiesStudy TypeRisk Estimate ReportedMBC RiskBRCA296 Cohort, 3 Case-controlOR, RR, CRStatistically significant increased risk (or lifetime CR > 6%) in 8/9 studiesCHEK277 Case-controlOR, RRVarying risk by variantBRCA163 Cohort, 3 Case-controlOR, RR, CR, HRStatistically significant increased risk in 1/6 studies, one study report lifetime CR = 5.8%PALB231 Cohort, 2 Case-controlOR, RRStatistically significant increased risk in 3/3 studiesATM11 Case-controlORStatistically significant increased risk in 0/1 studyOR: odds ratio; RR: relative risk; CR: cumulative risk; HR: hazard ratio Table 2: As an example: Reported penetrance of CHEK2 for male breast cancer in studies with varying ascertainment criteriaFirst Author, Year of Publication, Patient Population*Pathogenic VariantNumber of CarriersRisk TypeRisk Estimate (95% CI)Statistical SignificanceMeijers-Heijboer H, 2002, Multiple Countries1100delC57RR10.28 (3.54-29.87)YesSyrjakoski K, 2004, Finland1100delC28OR1.27 (0.04-7.92)NoWasielewski M, 2009, Netherlands1100delC21OR4.1 (1.2-14.3)YesPritzlaff M, 2017, USAAll441OR2.4 (1.4-3.9)Yes1100delC135OR3.8 (1.7-7.8)YesI157T238OR1.3 (0.5-3.0)NoHallamies S, 2017, Finland1100delC30OR4.47 (1.51-13.18)YesI157T104OR1.12 (0.4-3.13)NoLu HM, 2019, USANot specifiedNot specifiedOR1.66 (0.04-10.34)NoKleiblova P, 2019, Czech RepublicTruncations3OR20.21 (3.5-80.0)YesDeleterious missense1OR11.87 (0.25-100.83)NoIntermediate missense2OR1.3 (0.15-5.07)NoNeutral missense2OR9.07 (0.98-40.41)NoOR: odds ratio; RR: relative risk* All studies in Table 2 are case-control studies Citation Format: Reem S Chamseddine, Jin Wang, Kanhua Yin, Preeti Singh, Jingan Zhou, Danielle Braun, Mark E Robson, Kevin S Hughes. Penetrance of male breast cancer susceptibility genes: A systematic review [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-40.

Background: Natural killer (NK) cell-based adoptive immunotherapy is a promising approach for the treatment of cancer. But, it is difficult to generate the sufficient scale and purity of NK cells, and reliable methods to produce large number of functional NK cells have not been established yet. We have developed novel clinical-grade NK cells expansion method to produce the high purity, large scale and functional NK cells using a combination of recombinant human fibronectin fragment (RetroNectin®) -induced T-cells (RN-T cells), OK-432 and IL-2. We subsequently conducted a Phase 1 clinical study to evaluate the safety and efficacy of this NK cell therapy. In this paper, we address the characteristics of the NK cells elicited by this method and the results of immune monitoring in the clinical trial. Methods: To confirm the significance of RN-T cells as stimulator, we compared the stimulation effects on NK cells between RN-T cells and aCD3-T cells, which stimulated by anti-CD3 mAb only. Next, we analyzed expanded NK cells from PBMCs obtained from 31 cancer patients to verify the efficacy of this method. In the Phase 1 trial, patients with unresectable digestive cancer were enrolled. They received weekly intravenous administration of autologous NK cells elicited by the novel method three times to assess the safety of the number of adoptive cells at 0.5 × 109(cohort1), 1 × 109(cohort 2) and 2 × 109 cells (cohort 3) per dose. The phenotype and cytotoxicity of expanded NK cells were analyzed. For immune monitoring, cytotoxicity of PBMCs and whole blood cytokine levels were examined following NK cell infusion. Results: The stimulation by RN-T cells could induce preferable NK cell proliferation rather than the one by aCD3-T. As results of 31 cancer patients, 688±76-fold expansion was achieved in this system with PBMCs, and the NK cell populations were highly purified (84.7±3.6%) and highly expressed functional markers such as NKG2D (97.3±0.6%) and CD16 (96.8±0.7%). In the Phase 1 clinical trial, no NK cell infusion related severe or unexpected toxicities were observed. The response rate and the disease control rate in 10 per protocol patients were 0% and 50.0%, respectively. Although no clinical responses were observed, the cytotoxicity of PBMCs against K-562 targets increased in most patients (80%). The average of cytotoxic activity of PBMCs increased more than two times after the NK cell infusion. Conclusion: Although no patients receiving the NK cell therapy alone experienced a clinical response, adoptive immunotherapy of the NK cells elicited by the novel method is expected to exert considerable ADCC activity in vivo because of their high expression of CD16. Now, we are conducting clinical trial in which we explore the combination of this novel NK therapy with IgG1 antibodies such as trastuzumab and cetuximab. We also address the ongoing clinical trial in this paper. Citation Format: Takeshi Ishikawa, Naoyuki Sakamoto, Tetsuya Okayama, Kaname Oka, Satoshi Kokura, Mitsuko Ideno, Akiko Kato, Tatsuji Enoki, Masanari Kitagawa, Junichi Mineno, Tomoyo Yasuda, Toshifumi Doi, Yuji Naito, Yoshito Itoh, Toshikazu Yoshikawa. A novel expansion method for functional natural killer cells and its clinical application. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3137. doi:10.1158/1538-7445.AM2015-3137

Background: St Mary’s Hospital is an affiliated McGill Teaching University Hospital in Montreal, receiving ~700 new cancer patients yearly. In 2008, the oncology department implemented Patient Reported Outcomes (PROs) on paper. In 2014-17, electronic PROs were implemented through the Improving Patient Experience and Health in Outcomes Collaborative (iPEHOC) Implementation Project, as part of a PRO Canadian Initiative to improve the Patient Experience across the cancer journey through standardized measurement that accelerates optimal care and measures impact (health-related outcomes for patients) across Canada. Methodology: The PROs measures included the Edmonton Symptom Assessment Scale (ESASr), four additional secondary PROMs for Fatigue, Anxiety, Depression, and Pain, the Social Difficulties Inventory-21 and a single item Quality of Life. PRO data was scored in real-time; nurses and patients received a printed summary report. Nurses were provided with an algorithm (Global Response to Distress) and follow-up instructions. Monthly Distress Screening Dashboard ware generated with number of screenings, number of patients screened, symptom prevalence, secondary PROMs trigger rates, Social Difficulties triggered and clinically significant symptoms changes on the four secondary PROMs. In 2016, all patients receiving chemotherapy were assessed at each cycle of treatment (screening). After project completion, due to nursing staff shortage, the frequency of screenings was reduced and offered at pre-established time-points (assessment). Yearly Dashboard results were used to promote a discussion with clinicians and address sustainability constraints of PROs in real-word oncology practice. Results: In 2016, a total of 366 patients were screened, resulting in 1366 annual screens. In 2018, 325 patients were screened resulting in 753 annual screens. This change in practice, that culminated organically, allows for an observation analysis between screening versus assessment. Noteworthy comparison between 2018 and 2016 showed that the decrease in frequency of screenings resulted in significant increase in symptom severity in all health-related outcomes. Breast cancer represented 35% of all screens completed. We propose to present a three year retrospectively cross analyzed patient data to examine symptom change over time, frequencies of screening, the impact on patients’ health outcomes, the overlapping sustainability constraints encountered and mitigation plans. Discussion: Embedding the use of PRO into existing hospital structures requires constant review involving administrative, clinician and patient engagement. PRO data can be used to better identify the needs of a specific cancer type population and create tailored care paths. Citation Format: Ashley Kushneryk, Rosana Faria. Real-word implementation of patient report outcomes: Sustainability constraints and impact on patients health outcomes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-17-17.

Background: In India, most patients maintain a personal copy of their medical record in paper form which is hard to manage and collate. Newly diagnosed cancer patients and their doctors have an insurmountable task of consuming and using that information let alone centralizing the diagnosis, testing, and treatment information throughout the cancer care journey. Making this information available in an easy to consume format as well as recording a patient’s cancer experience is a technical challenge. We piloted an innovative mobile application to address this pain point for medical teams, patients and caregivers. Method: Pilot engagement was performed with 100+ patients of which 30 were female breast cancer patients seen for active treatment in 2019 at a non-profit oncology center in the suburb of New Delhi, India. Systematic medical information was captured on stage, TNM, hormone receptors, HER2 status, tumor size, tests, and treatments. We assessed the utility of the mobile application for the purpose of comprehensive cancer information management and ease of use by medical team, patient and their caregivers. Results: Data for a total of 30 female patients was captured. Patients were between the ages of 23 and 68, mean age 46. Of these patients, the cases were primarily late stage (III and IV) invasive ductal carcinoma. 26% of the women were Stage IV, 20% were Stage III, 26% were Stage II and 26% had not finished staging work-ups. One woman had inflammatory breast cancer and one woman was BRCA positive. Of the cases, 47% were HR+/HER2- cases, 20% were triple negative, and 13% of cases were HR+/HER2+. 20% had not yet received final pathologic assessment. The chemotherapy treatments included were doxorubicin, cyclophosphamide, carboplatin, paclitaxel, adriamycin, and epirubicin. Some of the women also were given radiotherapy. Clinic staff reported that the application was easy to use and helpful. We continue to enhance the application with staff feedback. Conclusion: We demonstrate feasibility and value of moving to a next generation digitized mobile platform circumventing the need for a traditional EMR system at a busy oncology clinic within a non-profit medical center in the suburb of New Delhi, India. Using the pilot, we make a case that this type of technology has the ability to transform cancer care for rural and low-resource health centers that are practicing on the frontlines of cancer care. We also demonstrate that it is easy to capture rich patient longitudinal data using this innovative platform. Citation Format: Rishi Gupta, Rohit Mahatma, Nayan Sonawane, Shilpa Mahatma, Tarun Kumar, Sharon Hensley Alford. An innovative approach to breast cancer patient engagement through frontline data capture and management using a mobile application for cancer diagnosis, test, and treatment at a non-profit tertiary cancer center in India [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-12-02.

Background: IOM, ASCO and Commission on Cancer have emphasized the provision of survivorship care plans (SCPs) to cancer patients. Cancer Care Ontario (CCO) aims to ensure that SCPs are developed and shared with healthcare providers (HCPs) to facilitate integrated cancer care. In 2016, a randomized mixed-methods study at St. Michael’s Hospital (SMH) provided a paper based Personalized Multifaceted Care Plan (PMCPs) to breast cancer (BC) patients, which included an upfront treatment plan. The PMCP was generated by entering non-repetitive patient data into a care plan database software developed by the team. The study results showed that patients and primary care providers (PCPs) found PMCP to be useful. Despite the benefits, implementation of SCPs as standard of care remained a challenge due to lack of designated personnel for developing SCP and limited resources causing poor provider buy-in. In 2017, we initiated a quality improvement (QI) project to implement the PMCP by integrating it into existing workflow by involving the care team. Methods: This REB approved QI project was done in two phases. Phase 1 was to identify key members to create the PMCP and to secure the software to the SMH IT server. In phase 2, the PMCPs were delivered to newly diagnosed invasive BC patients, receiving chemotherapy. The PMCPs were also shared with respective PCPs. At SMH, new patients diagnosed with BC are seen initially at the Multidisciplinary Clinic (MDC) by a medical and radiation oncologist, and a patient navigator (PN) to plan treatment. In phase 1, the PN who coordinated the MDC was identified as the most appropriate care team member to initiate the PMCP. To incorporate the PMCP into the PN’s existing workflow, a Transfer of Accountability (TOA) document was designed using the care plan software to replace a patient summary that was created in silos. The TOA was electronically shared with the team and had most of the information provided in the PMCP. The primary outcome measures were proportion of information completed to generate the PMCP and care plans delivered by patients’ care team. Secondary Outcome measures were patient and provider satisfaction with PMCP assessed using surveys at three time points and single time point respectively. Data were summarized using median and IQR as well as frequency and percentages. Data was also shared at QI team meetings, practice patterns were observed for changes and incorporated into subsequent PDSA cycles. Results: From 2017 to 2019, 90% (120/134) of eligible BC patients were provided with the PMCP. At the first 2 PDSA cycles 100% PMCP preparation and delivery was done by research staff. We have achieved 80% compliance in Phase 1 by involving the PN in data entry for PMCP while preparing the TOA document. TOA had been incorporated into standard of care at MDC and a recent nursing project found that HCPs surveyed perceived TOA to be a useful tool in information exchange and care coordination. Patient satisfaction surveys for PMCP found their responses were consistent over all time points with high levels of agreement. Surveys also showed that 73% (86/117) patients agreed that the PMCP helped with communication with their PCPs and 81% (95/117) agreed it helped with communication with the team. Of the 25 PCPs and 5 oncology HCPs surveyed, 91% (22/25) PCPs and 100% (5/5) oncology HCPs agreed that the PMCP should be incorporated into BC care. Conclusions: Implementation of SCPs with a multidisciplinary approach is feasible in BC care. Integration of SCPs within the existing work flow and involvement of members of the care team can lead to increased SCP uptake, better care coordination, sustainability and provider buy-in. With the high patient and provider satisfaction with PMCP, and recommendation by CCO, we are in the process of integrating PMCPs for BC patients as standard of care in the oncology clinic. Citation Format: Rashida Haq, Amy Kong, Ronita Lee, Geetha Mukherji, Christine Brezden-Maesley, Pauline Gulasingam. A multidisciplinary approach to implement personalized multifaceted care plans in standard breast cancer care: A quality improvement project [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-16.

Background: Breast cancer is a disease that can recur even after 20 years of diagnosis. At the moment it remains difficult to predict which women will have a late relapse as most scientific research is conducted for relapse within 10 years following diagnosis. A recent meta-analysis by Pan et al was the first to look at risk factors for relapse in the second decade after diagnosis. However this paper mostly included patients that were treated before the year 2000, which makes the results less applicable to patients nowadays. Objective: We retrospectively explored known early relapse risk factors for late relapse in a population that was diagnosed between year 2000 and 2008, 10-year disease-free and treated in one center. Patients and methods: We included all patients, diagnosed with invasive breast cancer who remained disease-free for 10 years. We selected these from a prospectively managed database of consecutive treated patients in the University Hospitals Leuven for early breast cancer, diagnosed between 01-01-2000 and 01-08-2008. We analyzed the association of patient and tumor characteristics for relapse during the second decade after diagnosis. A disease-free survival event (invasive or in situ) was defined as local (ipsi- and contralateral breast), loco-regional (ipsi- and contralateral axillary, internal mammary and subclavian lymph nodes) or metastatic. For the statistical analysis we used Cox proportional hazard models, with time to recurrence as response variable. Furthermore, a multivariable model of independent predictors was constructed using backward selection. Results: 2757 patients were included with a median follow-up of 13.78 years since initial diagnosis (range=10.01-18.65). Out of this group, 179 patients (6,5%) had a disease-free survival event (6 were in situ carcinoma). The multivariate analysis showed a higher risk of relapse in patients with a younger age (HR=1.044, p=0.0002), higher BMI (HR=1.036, p=0.0243) and postmenopausal status at diagnosis (HR=2.266, p=0.0012), higher tumor grade (HR=1.943, p=0.0151), more lymph node involvement (HR=1.626, p Conclusion: Several patient and tumor related factors proved to be significant independent risk factors for late relapse (>10 years after diagnosis). Our findings may help to differentiate between patients with high and low risk of relapse beyond 10 years of treatment and in this way, provide them with a more personalized form of follow-up. Citation Format: Anne-Sophie Vertongen, Hans Wildiers, Kevin Punie, Floris Giuseppe, Vergote Ignace, Patrick Berteloot, Toon Van Gorp, Ann Smeets, Els Van Nieuwenhuysen, Han Sileny, Ines Nevelsteen, Annouschka Laenen, Caroline Weltens, Hilde Janssens, Patrick Neven. Risk of breast-cancer recurrence after a 10-year disease-free interval [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-18.

Background: Leaving involved margins after mastectomy for breast cancer has been associated with an increased risk of local recurrence. Current guidelines endorse a policy that negative margins of no ink on tumour represent sufficient margin for local control and that the routine practice of obtaining a more widely negative margin is not indicated. We performed a systematic review of the literature and meta-analysis of studies analysing the impact of margin involvement after mastectomy on subsequent local recurrence. Methods: A systematic review was carried out searching MedLine, EmBase and ProQuest databases using the terms ‘mastectomy’, ‘resection margin’, ‘deep margin’, ‘margin status’ ‘fascia’ and ‘muscle invasion or infiltration’ from 1980 - 2019. In total 2,199 papers were screened and 33 studies were included in the quantitative synthesis. Statistical Methods: Meta-analysis was conducted using random effects modelling, pooling hazard ratios (HR), and odds ratios (OR) from binary outcome data. The associations between positive margins and local recurrence were stratified by positive margin distance and analysed according to use of adjuvant radiotherapy and follow up duration. Results: In total 37,738 patients, with a median age of 54.5 years, were included in the quantitative synthesis. Positive margins were associated with increased local recurrence on univariable analyses (HR 2.99, 95%CI: 2.99, 2.15 - 4.15), multivariable adjusted analyses (HR, 2.61, (95%CI 2.03-3.35) (which included Molecular Phenotype, Stage and Node status) as well as binary outcome data (OR, 95%CI: 2.75, 1.94-3.88). Positive margins were consistently associated with increased local recurrence, regardless of the distance of the tumour from the margin defined as positive (HR, 95%CI, tumour at ink: 2.39, 1.53-3.72; margin 5 years compared to 5 years OR 3.50, 2.13 - 5.75). Data were available from five studies for patients not receiving radiotherapy. In this subgroup positive margins were associated with a 3-fold risk of local recurrence (OR: 3.01, 1.96-4.61). Conclusions: On meta-analysis the risk of local recurrence after mastectomy is associated with margin proximity. Most data on margin status has related to breast conserving surgery. Adequate surgical margin clearance greater than 2mm margin after mastectomy is required to prevent local recurrence and International guidelines should reflect this finding. Citation Format: James Bundred, Sarah Michael, Sarah Bowers, Nicola Barnes, David Dodwell, Yasmin Jauhari, Nigel Bundred. Do surgical margins matter after mastectomy? A meta-analysis of 37,738 breast cancer patients in 33 studies [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-07.

Background: Palbociclib in combination with endocrine therapy (ie, an aromatase inhibitor [AI] or fulvestrant) is a current standard of care for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer (ABC/mBC). Findings from the PALOMA clinical trials have shown that patients receiving palbociclib with AI or fulvestrant maintained stable quality of life (QoL). However, no data are currently available from real-world settings regarding patients’ QoL experiences while receiving palbociclib. Methods: This noninterventional, prospective, multicenter study evaluated female and male patients diagnosed with HR+/HER2- ABC/mBC and treated with palbociclib as indicated by the attending physician in the routine course of care. QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 was collected at enrollment prior to receiving palbociclib (baseline), monthly for the first 3 months of treatment with palbociclib, and then every 3 months until the end of treatment or patient withdrawal or death. The EORTC QLQ-C30 could be completed using an interactive Web response system or a paper questionnaire. Here we report demographic characteristics and interim analysis of QoL assessments as measured by EORTC QLQ-C30 at baseline and at 3 and 6 months postbaseline. Descriptive analyses are presented for subscales of the EORTC QLQ-C30. Results: 522 patients who completed ≥6 months of palbociclib treatment as of May 20, 2019, were included in this interim analysis; 394 were prescribed palbociclib as first-line treatment. The remaining 128 patients initiated palbociclib in second and later lines. Median age at enrollment was 64 years, 98% of patients were female, and 83% were white. More than half of all patients (n=285) received palbociclib in combination with letrozole or anastrozole; of the remaining patients, 218 received palbociclib plus fulvestrant and 19 received palbociclib plus exemestane. Mean (SD) EORTC QLQ-C30 scores remained similar over the first 6 months of treatment: 66.2 (22.6) at baseline, 68.3 (19.7) at 3 months, and 70.2 (21.3) at 6 months. In addition, the mean scores for each functional scale and symptom scale on the EORTC QLQ-C30 also remained stable over the first 6 months (Table). With the exception of pain scores (which declined by 7 points), the change from baseline at 6 months generally was less than 5 points across the different subscales of EORTC QLQ-C30. Conclusions: The 522 patients examined in this interim analysis experienced stable to modestly improved QoL from baseline to 6 months after starting palbociclib. Changes from baseline in EORTC QLQ-C30 scores generally were below the 10-point threshold regarded as clinically meaningful. These early findings indicate that patients enrolled in the study have maintained their baseline QoL while being treated with palbociclib. Funding: Pfizer (NCT03280303) EORTC QLQ-C30Baseline3 Months6 MonthsGlobal Health/Quality of Life*n (missing)474 (48)292 (230)409 (113)Mean (SD) score66.2 (22.6)68.3 (19.7)70.2 (21.3)Functional scales score, mean (SD)*Physical functioning75.6 (23.3)75.8 (21.9)77.2 (21.4)Role functioning72.5 (31.9)76.7 (26.1)77.1 (26.8)Emotional functioning74.8 (22.8)77.7 (22.3)79.7 (20.5)Cognitive functioning78.8 (24.6)82.7 (20.6)80.1 (22.0)Social functioning76.4 (28.3)79.5 (25.5)81.5 (24.7)Symptom scales score, mean (SD)†Fatigue34.3 (25.7)35.0 (23.6)33.7 (22.2)Nausea and vomiting11.3 (20.2)10.4 (16.4)10.6 (19.3)Pain33.5 (30.0)27.3 (27.2)26.5 (26.9)Dyspnea22.2 (28.3)18.7 (22.5)18.8 (24.1)Insomnia29.3 (30.1)27.5 (31.7)27.4 (27.9)Appetite loss21.1 (27.9)19.4 (26.4)17.9 (26.5)Constipation18.4 (26.6)15.2 (23.8)16.0 (23.8)Diarrhea12.3 (22.1)12.0 (20.8)12.6 (22.0)Financial difficulties25.0 (32.4)23.9 (30.4)22.1 (29.5)*Higher scores indicate a better level of functioning. †Higher scores indicate more severe symptoms. Citation Format: Gabrielle Rocque, Joanne L Blum, Aldemar Montero, Ibrahim Nakhoul, Sobha Kurian, Richard C Frank, Bijoy Telivala, Mayank Ajmera, David Coblentz, Joseph C Cappelleri, Yao Wang, Debu Tripathy. Quality of life in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer treated with palbociclib in real-world practice settings [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-03.

Background: Abemaciclib is an orally administered inhibitor of cyclin-dependent kinase (CDK) 4/6, dosed twice daily (BID) on a continuous schedule. Diarrhea is a frequently associated adverse event. It is predictable and manageable with antidiarrheal medication, typically occurs within the first month of therapy, and decreases over the duration of treatment. In the MONARCH 1, 2, and 3 studies, Grade 3 diarrhea was experienced by 9% to 20% of patients (pts) receiving abemaciclib. Study design/Objectives: Study I3Y-MC-JPCP (ClinicalTrials.gov, NCT03703466) was a multicenter, randomized, open-label phase 2 study designed to evaluate the impact of food on the incidence of Grade 3 or prolonged Grade 2 diarrhea in HR+, HER2− metastatic breast cancer (mBC) pts receiving abemaciclib monotherapy 200 mg orally BID during the first 3 cycles of study treatment. Methods: Pts with HR+, HER2− mBC and ECOG performance status ≤1 who had progressed after prior anti-estrogen therapy for mBC and received prior treatment with ≥1 chemotherapy regimen for mBC, but were CDK4/6i naive, were randomly assigned 1:1:1 to receive abemaciclib with a meal, in a modified fasted condition (defined as ≥1 h before or ≥2 h after a meal), or without regard to food. Primary study endpoints were the incidence of ≥Grade 3 diarrhea; incidence of Grade 2 diarrhea lasting >7 days; dose reductions, dose interruptions, and treatment discontinuations due to diarrhea; and use of antidiarrheal agents. Secondary endpoints included overall safety and pharmacokinetic analysis. A pt-held electronic diary was used to record daily information on number of stools, diarrhea, loperamide use, and timing of abemaciclib intake relative to meals. Compliance with diary completion was centrally monitored. Multicenter training and implementation of e-diaries used a variety of paper and electronic resources tailored to end user (research staff, site staff, patient). Physicians had real-time access to data enabling accurate assessment of diarrhea. Results: This study randomized 72 pts in five countries from December 2018 to April 2019; 71 pts (median age 56.0 y) were treated with abemaciclib in one of three study arms: with a meal (Arm 1, n=24), modified fasted condition (Arm 2, n=23) and without regard to food (Arm 3, n=24). Mean compliance for e-diary completion was 95.7% for the overall population. Mean compliance with meal conditions was 99.5% in Arm 1 and 95.2% in Arm 2 (not applicable for Arm 3). In Arms 1, 2 and 3, 83.3%, 78.3% and 91.7% of pts received ≥3 cycles, respectively. Primary endpoints during the first three treatment cycles are summarized (Table). Table 1Arm 1 (n=24)Arm 2 (n=23)Arm 3 (n=24)Overall (n=71)≥1 Grade 2 diarrhea lasting >7 days, %8.317.420.815.5≥1 Grade 3 diarrhea, %4.2*001.4≥1 Grade 4 diarrhea, %0000≥1 Dose reduction due to diarrhea, %16.78.712.512.7≥1 Dose interruption due to diarrhea, %16.74.38.39.9Treatment discontinued due to diarrhea, %0000Loperamide use, %95.891.395.894.4* Duration of Grade 3 diarrhea was 1 day. This study was descriptive and not powered to analyze differences between study arms. Overall, the most frequently reported Grade 3/4 treatment-emergent adverse events related to treatment were neutropenia (28.2%), leukopenia (11.3%), thrombocytopenia (7.0%), fatigue (5.6%), nausea (5.6%) and lymphopenia (5.6%). Details on patient-reported diarrhea incidence and management, and PK analyses will be presented at conference. Conclusions: Global compliance with e-diary completion and meal condition was >95%. Diarrhea at high grade occurred at much lower incidence than previously reported (1.4% overall) and was of short duration (1 day). Diarrhea was predominantly low grade and managed with loperamide and dose modifications in all meal cohorts. Citation Format: Elgene Lim, Frances Boyle, Meena Okera, Sherene Loi, Sema Sezgin Goksu, Gertjan van Hal, Daisy G Hartman, Jonathon Colby Gable, Gregory L Price, Anwar Hossain, M C Gainford, Meritxell Bellet Ezquerra. The impact of food on tolerability of abemaciclib in patients with previously treated hormone receptor-positive, HER2-negative, metastatic breast cancer: An open-label, randomized phase 2 study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-05.

Rationale: Breast cancer diagnosis at a young age is associated with higher risk of recurrence, second malignancy, mortality, morbidity, and impact on quality of life. Young breast cancer survivors face more life-years after treatment, with associated financial, emotional, and physical burdens. Long-term effects of treatment may include early menopause, fertility impairment, neuropathy, cardiovascular disease, lowered bone density, and risk of second malignancies. Young women with or at-risk for breast cancer often seek health information through mainstream print and digital media. However, they often find it does not address their unique concerns, is difficult to interpret, or even misleading. Media reports of breast cancer research are often unreliable, misleading, or confusing regarding which information is clinically relevant. Common flaws include exaggerating prevalence, ignoring potential side effects of treatment, and failing to discuss all treatment options. Young women with or at-risk for breast cancer, need accurate, clearly presented information based on sound evidence to help them make informed decisions about their specific health needs. To help women better understand media coverage about new research, Facing Our Risk of Cancer Empowered (FORCE) developed the CDC-funded XRAYS (eXamining Relevance of Articles to Young Survivors) program. XRAYS is an online resource that provides brief articles summarizing recent research relevant to young women with or at-risk for breast cancer. XRAYS articles rate the quality and relevance of research, the quality of media reporting, and suggest questions that may be useful to address with health care providers. One critical aim of XRAYS is to improve users’ understanding of the limitations of research methods and of media reporting. FORCE charged an independent evaluator with conducting an assessment of XRAYS’ effects on users’ understanding of methodological and reporting issues in media articles about research related to breast cancer. Objective: The objective of this study was to assess whether XRAYS improves readers’ understanding of limitations of study methods and media reporting more than reading media reports alone. Methods: To assess XRAYS’ impact on users’ understanding of limitations in research methods and reporting quality, an independent evaluator conducted a study with 36 volunteer participants who were attending a FORCE conference. Participants were randomly assigned to treatment or control groups. The treatment group read a media report and the corresponding XRAYS article. The control group read only the media report. After reading the materials, participants answered paper and pencil multiple choice questions about methodological limitations of the research discussed in the media report, and about limitations of the reporting itself. Results: Results are summarized in the table. GroupNMean Score (s.d.)t-score (d.f.)PComparison Group1742.85 (19.85)-3.08 (34) After reading the media article, the control group, on average, correctly identified fewer than half of the limitations in study methods or reporting, while, on average, after reading the media article with an XRAYS summary, the treatment group identified about two-thirds of the limitations. The difference between treatment and control groups was statistically significant. Conclusion: Results indicate that XRAYS is effective in supporting users in identifying more limitations in research and reporting than people who read media reports alone. Citation Format: Robin Hilary Pugh Yi, Piri Welcsch, Lisa Rezende, Craig Dearfield Ph.D., Kelly Owens, Susan J. Friedman. Effects of an online educational resource on lay audience understanding of limitations of quality in media reports and research methods [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-06.

In this study we have examined how the cytokine interleukin-2 (IL-2) synergizes with programmed cell death-1 (PD-1) directed immunotherapy during chronic lymphocytic choriomeningitis virus (LCMV) infection. PD-1 blockade in combination with IL-2 is one of the most effective combination therapies in this very stringent LCMV mouse model of life-long chronic infection with irreversible T-cell exhaustion. Our paper makes the following points: First, we show that the more effective viral control seen after PD-1 + IL-2 combination therapy compared to PD-1 monotherapy is mediated by the CD8+ T-cell response. Then we identify the virus-specific CD8+ T cells that proliferate and respond to the combination therapy and show that these are the same lymphoid resident PD-1+ TCF-1+ stem-like CD8+ T cells that act as resource cells to maintain the CD8+ T-cell response during chronic infection and also respond to PD-1 blockade. However, the combination therapy dramatically changes the differentiation program of these chronic resource CD8+ T cells and results in the generation of transcriptionally and epigenetically distinct effector CD8+ T cells that resemble highly functional effector CD8+ T cells seen after an acute viral infection. In contrast, PD-1 monotherapy does not modify the differentiation program and one gets more virus-specific CD8+ T cells but they are transcriptionally and epigenetically similar to what is seen in untreated chronically infected mice. This epigenetic inflexibility of exhausted CD8+ T cells is a potential barrier to PD-1 therapy and the ability of this combination therapy to modify the epigenetic signature of virus-specific CD8+ T cells during chronic infection could be an important determinant of the striking synergy seen between IL-2 therapy and PD-1 blockade. We also highlight the importance of blocking the PD-1/PD-L1 inhibitory pathway at the target site for effective viral control. Expanding the CD8+ T cell population and generating better effector cells is important but it is also critical to block PD-1 inhibitory signals at the target site for optimal immunotherapy. Finally, we show that CD25 engagement with IL-2 plays an important and essential role in the observed synergy between IL-2 cytokine and PD-1 blockade. Either blocking CD25 with an antibody or using a mutated version of IL-2 that does not bind CD25 but still binds CD122/132 almost completely abrogated the synergistic effects seen after PD-1/IL-2 combination therapy. There is currently considerable interest in PD-1 + IL-2 combination therapy for cancer patients and our fundamental studies defining the underlying mechanisms of how IL-2 synergizes with PD-1 blockade should inform these human translational studies. Citation Format: Masao Hashimoto. Understanding how IL-2 cytokine synergizes with PD-1 therapy during chronic viral infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB100.