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This is the schema of the clinical study design. This is a Phase 2 trial of TM in breast cancer at high risk of recurrence. Eligible patients received TM for 2 years to achieve a target CP level of < 17 mg/dL. Primary endpoint was effect on VEGFR2+ EPCS.

This is the demographics table containing brief summary of baseline patient characteristics of patients enrolled on trial.

This section contains details of all mixed models utilized in the statistical analyses. The inferential tests performed in this paper necessitates a multiple comparisons adjustment, and details of the adjustment procedure is included in this section as well.

Purpose: Bone marrow–derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models.Experimental Design: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition.Results: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II–III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012).Conclusions: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted.

This is the demographics table containing detailed baseline patient characteristics listed for each of the 75 patients. The data is de-identified.

To address the need for cost-of-care conversations in prenatal care, the CONTINUE (cost conversations inroutineprenatal care) study was conducted with prenatal patients to better understand the benefits of implementing a cost-of-care conversation “cost” tool into routine obstetrics (OB) care. This research team conducted a multi-phase, mixed-methods research study to identify 18 target benefits of a cost tool to initiate and standardize cost-of-care conversation and, subsequently, developed and validated a cost tool. The cost tool was piloted and data pertaining to cost tool benefits were collected through interviews and surveys. To comprehensively assess the cost tool’s utility, exploratory factor analysis was performed to classify the underlying factor structure of the 18 benefit item responses. Data includes patients’ self-reported experiences of benefit items, as collected from third trimester prenatal patient participants who received the tool at the beginning of their prenatal care in three midwestern-based hospital clinics within one healthcare system. The present study describes the factor analysis approach used to identify the three final factors that emerged from the data. This analysis provides a framework for exploring patient-specific predictors of experiencing the benefit-related factors of a cost tool incorporated into routine OB care.Statements and DeclarationsThis study was funded by the Robert Wood Johnson Foundation, #77290.

Background Patient navigation is an increasingly widespread intervention to address the persistent, severe, and disproportionate breast cancer (BC) burden that African Americans (AA) face. Navigation may have more widespread effects than previously estimated due to patient-driven diffusion of BC information. Methods This pilot study examined the network effects of a randomized controlled trial via recruitment of navigated and non-navigated AA BC patients as well as their network members. We estimated study arm differences in patient BC promotion (i.e., number of individuals to whom BC patients promote BC screening) and network BC screening (i.e., % BC screening among network members). Results Among our sample of 100 AA BC patients, navigated patients promoted BC screening to more individuals than non-navigated patients. BC patients were more likely to promote BC screening to children and individuals with whom they communicated more frequently. Some models further suggested more network BC screening among "navigated" network members relative to "non-navigated" network members. Conclusions Navigated AA patients promoted BC screening more widely throughout their networks than non-navigated AA BC patients. There were also suggestive findings regarding increased BC screening among their network members. Our pilot study highlights the potential for social network analysis to improve the precision of intervention effect estimates and to inform future innovations (e.g., integrating navigation and network-based interventions) with multilevel effects on cancer health disparities.

Purpose Given the current life expectancy and number of individuals living with Down syndrome (DS), it is important to learn common occurrences of disease conditions across the developmental lifespan. This study analyzed data from a large cohort of individuals with DS in an effort to better understand these disease conditions, inform future screening practices, tailor medical care guidelines, and improve utilization of health care resources. Methods This retrospective, descriptive study incorporated up to 28 years of data, compiled from 6078 individuals with DS and 30,326 controls matched on age and sex. Data were abstracted from electronic medical records within a large Midwestern health system. Results In general, individuals with DS experienced higher prevalence of testicular cancer, leukemias, moyamoya disease, mental health conditions, bronchitis and pneumonia, gastrointestinal conditions, thyroid disorder, neurological conditions, atlantoaxial subluxation, osteoporosis, dysphagia, diseases of the eyes/adnexa and of the ears/mastoid process, and sleep apnea, relative to matched controls. Individuals with DS experienced lower prevalence of solid tumors, heart disease conditions, sexually transmitted diseases, HIV, influenza, sinusitis, urinary tract infections, and diabetes. Similar rates of prevalence were seen for lymphomas, skin melanomas, stroke, acute myocardial infarction, hepatitis, cellulitis, and osteoarthritis. Conclusions While it is challenging to draw a widespread conclusion about comorbidities in individuals with Down syndrome, it is safe to conclude that care for individuals with DS should not automatically mirror screening, prevention, or treatment guidelines for the general U.S. population. Rather, care for those with DS should reflect the unique needs and common comorbidities of this population.

Objectives Increased exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a result of having an essential job is compounded by factors such as age, race, and ethnicity. We used a cross-sectional study design to describe disparities in the seroprevalence of SARS-CoV-2 immunoglobulin G (IgG) test results by demographic characteristics and clinical roles among a cohort of health care workers employed by the largest Midwestern health care system in the United States. Methods We collected 16 233 SARS-CoV-2 IgG serum samples from June 8 through July 10, 2020, from a convenience sample of Illinois- and Wisconsin-based adult health care workers. The research team, in collaboration with ACL Laboratories, used a SARS-CoV-2 IgG assay to detect the presence of SARS-CoV-2 IgG antibodies. Study data included SARS-CoV-2 IgG assay results and demographic characteristics of workers (age, sex, race, ethnicity, clinical role, zip code). We generated crude and adjusted odds ratios (ORs) to describe disparities in seroprevalence distribution among demographic and social factors. Results Of 16 233 IgG serum samples tested, 622 (3.8%) test results were positive for SARS-CoV-2. We found significant disparities in SARS-CoV-2 positivity by age, race, ethnicity, and clinical role. Participants aged 32-82 had lower adjusted ORs (aORs) of positive IgG than participants aged 18-31 (aOR range, 0.54-0.66). Odds of positivity were higher among Black (aOR = 3.86), Asian (aOR = 1.42), and mixed-race (aOR = 1.99) workers than among White workers; among Hispanic workers (aOR = 1.80) than among non-Hispanic workers; and among coronavirus disease 2019 (COVID-19) clinical workers (aOR = 1.86) than among nonclinical workers. Conclusions Public health efforts should focus on increasing COVID-19 safety messaging, testing, vaccination, and other prevention efforts for people who are young, non-White, Hispanic, and working in COVID-19–clinical units.

PURPOSE: Social support improves several quality of life (QOL) domains among African American breast cancer survivors. Further, how different dimensions of social support are associated with QOL among African American breast cancer survivors may differ from other populations. This study explores this hypothesis by examining associations of positive social support (supportive interactions that promote affection) and negative social support (non-supportive interactions or interactions wherein the provider of support may not have the best intended actions) with QOL among Chicago-based African American breast cancer survivors. METHODS: Study participants were eligible if they: 1) identified as being an African American female, 2) were at least 18 years of age or older, and 3) were diagnosed with breast cancer during or after navigation was implemented at the study hospital. Participants completed validated questionnaires via telephone or in-person interviews. RESULTS: Among our sample of 100 participants, positive support was associated with greater mental well-being in non-imputed (Std β=1.60, CI: 0.51, 2.69, p= 0.004) and imputed models (Std β= 1.67, CI: 0.68, 2.73, p=0.001). There was also a weaker inverse association with negative support and mental well-being when using non-imputed data (Std β=−0.82, CI: −1.65, 0.02, p= 0.05). CONCLUSIONS: Our findings suggest that positive support, in particular, is highly influential for improving mental well-being among African American breast cancer survivors. Simultaneously, negative support appears to be an independent, albeit weaker, determinant of mental well-being.

The aim of the study is to identify factors associated with breakthrough infection among a cohort of Midwestern healthcare personnel (HCP).SARS-CoV-2-positive test results between March 1, 2020, and July 31, 2021, were collected from electronic medical records of HCP to identify breakthrough infections.Healthcare personnel who were younger than 35 years, received the Pfizer vaccine, and worked in COVID clinical units had greater adjusted odds of breakthrough infection. COVID infection before full vaccination was associated with reduced odds of breakthrough infection.Our study concluded that the most vulnerable HCP are younger, working in COVID-19 clinical units, and received Pfizer-BioNTech primary series vaccines. Healthcare personnel who had COVID before vaccination were at reduced risk of breakthrough infection, indicating that supplemental immunity could better protect at-risk HCP groups.

Objectives The objective of this study is to explore the characteristics of the subset of patients with hematologic malignancies (HMs) who had little to no change in SARS-CoV-2 spike antibody index value levels after a third mRNA vaccine dose (3V) and to compare the cohort of patients who did and did not seroconvert post-3V to get a better understanding of the demographics and potential drivers of serostatus. Study design This retrospective cohort study analyzed SARS-CoV-2 spike IgG antibody index values pre and post the 3V data on 625 patients diagnosed with HM across a large Midwestern United States healthcare system between 31 October 2019 and 31 January 2022. Methods To assess the association between individual characteristics and seroconversion status, patients were placed into two groups based on IgG antibody status pre and post the 3V dose, (−/+) and (−/−). Odds ratios were used as measures of association for all categorical variables. Logistic regressions were used to measure the association between HM condition and seroconversion. Results HM diagnosis was significantly associated with seroconversion status (P = 0.0003) with patients non-Hodgkin lymphoma six times the odds of not seroconverting compared with multiple myeloma patients (P = 0.0010). Among the participants who were seronegative prior to 3V, 149 (55.6%) seroconverted after the 3V dose and 119 (44.4%) did not. Conclusion This study focuses on an important subset of patients with HM who are not seroconverting after the COVID mRNA 3V. This gain in scientific knowledge is needed for clinicians to target and counsel these vulnerable patients.

ImportanceGiven the overwhelming worldwide rate of infection and the disappointing pace of vaccination, addressing reinfection is critical. Understanding reinfection, including protection longevity after natural infection, will allow us to better know the prospect of herd immunity, which hinges on the assumption that natural infection generates sufficient, protective immunity. The primary aim of this paper is to provide data on SARS-CoV-2 reinfection over a 10-month period.ObjectiveThe primary objective of this study is to establish the incidence of reinfection of COVID-19 among healthcare employees who experienced a prior COVID-19 infection.DesignThis observational cohort study followed a convenience sample of 2,625 participants who experienced a COVID-19 infection for subsequent COVID-19 infection.SettingHealthcare employees were recruited across a large Midwestern healthcare system. Positive PCR test results were administered and recorded by the system-affiliated lab serving Illinois and Wisconsin.ParticipantsAdult healthcare system employees who enrolled in a research study focused on SARS-CoV-2 antibodies (N = 16,357) and had at least one positive PCR test result between March 1, 2020 and January 10, 2021 were included (N = 2,625).ExposurePositive PCR test for SARS-CoV-2Main Outcome(s) and Measure(s)The primary outcome is incidence of COVID-19 reinfection, defined by current CDC guidelines (i.e. subsequent COVID-19 infection ≥ 90 days from prior infection). COVID-19 recurrence, defined as subsequent COVID-19 infection after prior infection irrespective of time, is also described.ResultsOf 2,625 participants who experienced at least one COVID-19 infection during the 10-month study period, 156 (5.94%) experienced reinfection and 540 (20.57%) experienced recurrence after prior infection. Median days were 126.50 (105.50-171.00) to reinfection and 31.50 (10.00-72.00) to recurrence. Incidence rate of COVID-19 reinfection was 0.35 cases per 1,000 person-days, with participants working in COVID-clinical and clinical units experiencing 3.77 and 3.57 times, respectively, greater risk of reinfection relative to those working in non-clinical units. Incidence rate of COVID-19 recurrence was 1.47 cases per 1,000 person-days.Conclusions and RelevanceThis study supports the consensus that COVID-19 reinfection, defined as subsequent infection ≥ 90 days after prior infection, is rare, even among a sample of healthcare workers with frequent exposure.

Patient navigation is an increasingly widespread intervention to address the persistent, severe, and disproportionate breast cancer (BC) burden that African Americans (AA) face. Navigation may have more widespread effects than previously estimated due to patient-driven diffusion of BC information.This pilot study examined the network effects of a randomized controlled trial via recruitment of navigated and non-navigated AA BC patients as well as their network members. We estimated study arm differences in patient BC promotion (i.e., number of individuals to whom BC patients promote BC screening) and network BC screening (i.e., % BC screening among network members).Among our sample of 100 AA BC patients, navigated patients promoted BC screening to more individuals than non-navigated patients. BC patients were more likely to promote BC screening to children and individuals with whom they communicated more frequently. Some models further suggested more network BC screening among "navigated" network members relative to "non-navigated" network members.Navigated AA patients promoted BC screening more widely throughout their networks than non-navigated AA BC patients. There were also suggestive findings regarding increased BC screening among their network members. Our pilot study highlights the potential for social network analysis to improve the precision of intervention effect estimates and to inform future innovations (e.g., integrating navigation and network-based interventions) with multilevel effects on cancer health disparities.

e19513 Background: Patients (Pts) with hematologic malignancies (HM) are at greater risk of severe morbidity and mortality caused by COVID19 and show a lower response to the two-dose COVID19 mRNA vaccine series. The primary vaccine series now includes a third dose of the COVID19 vaccine (3V) for immunocompromised Pts. The objective of this study was to explore the characteristics of HM patients who had no change in SARS-CoV-2 spike protein titer levels post 3V (-/-) to gain a better understanding of the drivers of serostatus. Methods: This retrospective cohort study analyzed Pt data on SARS-CoV-2 spike IgG antibody titers pre- and post- 3V across the healthcare system. This study included 268 fully vaccinated HM Pts diagnosed with HM between October 31, 2019 and January 31, 2022 and had a negative serostatus prior to 3V. Post 3V titers were obtained 21 days after 3V. Demographics, association between characteristics and seroconversion status, and odds ratios were all assessed (table). Results: Pts with Non-Hodgkin lymphoma (NHL) had 6 times the odds of not seroconverting compared to multiple myeloma (MM) (CI 1.88 – 19.12, P = .0010). NHL also have about 14 times the odds of not seroconverting compared to Pts diagnosed with other HM conditions, which included: neoplasms of uncertain behavior and disorders of white blood cells (CI 1.72 – 112.44, P = .0021). 90% of seronegative Pts showed no spike IgG antibody reaction to 3V as indicated by pre- and post- 3V index values. Demographics, previous COVID19 infection, and vaccine type were not significantly associated with seroconversion. Conclusions: HM patients who are not seroconverting after 3V, suggest a prioritized population for continued increased behavioral precautions, additional vaccination efforts, including a fourth dose of an mRNA COVID19 vaccine, as well as passive immunity boosting through monoclonal and polyclonal antibodies.[Table: see text]

Introduction: Standard economic evaluation methods may underestimate the value of health equity interventions by focusing exclusively on program costs and direct effects on participants' health. Yet, these interventions have spillover effects – wherein participants transition from being intervention recipients to becoming health advocates for their social networks. Consequently, interventions may improve the health of participants and other community members who are not directly connected with interventions. This study demonstrates the utility of incorporating spillover effects by comparing incremental cost-effectiveness ratios via a patient navigation intervention to promote mammography screening among African American (AA) women. Specifically, we compare the relative costs and cost-effectiveness when including mammography uptake of: (1) AA intervention participants (egos) only versus (2) AA intervention participants (egos) and their screening eligible social network members (alters). Methods: Our study draws from two studies: (1) an individual randomized trial to test the efficacy of patient navigation on mammography uptake (Patient Navigation in Medically Underserved Areas [PNMUA]) and (2) an observational ancillary study to test the effects of PNMUA on breast cancer survivor egos and their alters (Offering AA Survivors Increased Support [OASIS]). Overall, we used a healthcare system perspective. For 2021 cost data, we collected data from study records and expense reports. For effects data, we used: (1) medical record data for egos' mammography uptake, (2) self-report data from egos regarding their alters' mammography uptake, and (3) self-report data from alters about their own mammography uptake. We consequently computed incremental cost-effectiveness ratios (ICERs), using different data sources, to assess the impact of estimating spillover effects on economic evaluation of patient navigation. Results: Total cost of the intervention was $196,601. The greatest expense were breast cancer navigators' salaries and fringe rates ($126,745). In PNMUA, more navigated vs. non-navigated egos obtained biennial mammograms (45% vs. 39%). In terms of spillover effects, more navigation arm alters obtained biennial mammograms compared to alters in the non-navigated arm (ego self-report: n=1296 vs 949; alter self-report: n=1521 vs. 1195). Navigation had lower value when only incorporating participants' mammography uptake ($3,277 per each additional woman screened) versus when incorporating spillover effects ($2,027-$2,114 per each additional woman screened). Conclusion: Our results suggest breast cancer navigation programs may be more valuable when including spillover effects. This case study provides insight with real-world applicability into integrating spillover effects into economic evaluation. Our methods offer a new avenue for improved cost and effect estimates of health equity interventions, which may be useful for assessing future resource allocation in healthcare practice and policy. Citation Format: Nyahne Bergeron, Veronica Fitzpatrick, Carl Asche, Karriem S. Watson, Aditya S. Khanna, Bridgette Hempstead, Elizabeth A. Calhoun, Jean McDougall, Yamilé Molina. The value of estimating spillover effects in health equity interventions: A case study to promote mammogram uptake among African American women and their social networks [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-208.

This paper examines the epidemiology of nonfatal firearm violence (NFFV) on the Westside of Chicago over three finite time periods: 2005–2008, 2009–2012, and 2013–2016. The trend analysis will look at any significant changes over the time periods and describe the demographic characteristics of NFFV. A descriptive analysis of Mount Sinai Hospital (MSH) Emergency Department (ED) data was conducted. NFFV patients were identified by specific firearm ICD-9 primary eCode injury categories: accident, assault, legal intervention, undetermined intent, suicide or self-inflicted injury, and legal intervention. The Pearson Chi-square test was conducted to statistically compare the categorical frequencies of the Chicago metropolitan region of injury, cause of firearm related injury, and place of injury by time period. There were a total of 3962 nonfatal hospitalizations at MSH between the three time periods due to gun violence related injuries. Overall, nonfatal hospitalizations were most frequent for those between age groups 16–24 (52.5%). The number of nonfatal hospitalizations decreased with increasing age for the age groups 35–44 (9.7%), 45–54 (3.2%), and > 54 (1.2%). There were significantly more nonfatal hospitalizations in males (n = 3649) than females (n = 312) across the three time periods. However, there was a 74.7% increase in female nonfatal hospitalizations from 2009–2012 to 2013–2016. There were significant racial differences in nonfatal hospitalizations between the three time periods. NFFV continues to be problem on the Westside of Chicago, particularly for young, Black men. The incidence of gun violence however has not changed significantly between 2005 and 2016.

Background: Tumor infiltrating lymphocytes (TILs) evaluated in the primary tumor biopsy or surgical resection have been well established as having prognostic significance in patients with triple negative breast cancer (TNBC) and HER2+ breast cancer treated with adjuvant chemotherapy (Savas et. al, Nat Rev Clin Oncol 2016). In TNBC, stromal TILs behave as a continuous variable with every 10% increase in TIL resulting in a decrease in risk of recurrence and death. The definition of lymphocyte-predominant breast cancer (LPBC) has been used for tumors that contain 50%–60% TILs and usually have a particularly good outcome (Salgado et al, Ann Oncol 2015). Our group recently demonstrated in a phase II single arm study that tetrathimolybdate (TM), a copper-depleting agent, resulted in improved event free survival (EFS) for TNBC patients compared to historical controls. The 2-year event-free survival (EFS) for stage 2-3 and stage 4 NED was 91% and 67%, respectively. In this analysis, our goal was to explore whether the encouraging results we observed were influenced by enrolling TNBC patients with better prognostic factors at initial diagnosis, namely higher stromal TIL score, in our copper depletion trial. Methods: Archived primary breast tissue was available from 67 of the 75 patients enrolled in the phase II TM trial. The phase II study included patients with stage II TNBC or stage III or IV NED breast cancer patients, who were treated with TM for 2 years or until relapse. Here we focused on the 30 patients with TNBC. The demographic data for the patients is included in the following table. Patient DemographicsAge at diagnosisStage at study entryPrior Adjuvant or Neoadjuvant therapyNumber of prior chemotherapy regimens in metastatic setting%Tumor Infiltrating Lymphocytes504Adjuvant110543AAdjuvantn/a30563AAdjuvantn/a20513CNeoadjuvantn/a The number of TILs in each sample was calculated by an experienced pathologist using published criteria (Salgado et al, Ann Oncol 2015). We used TILs >50% to define LPBC. Results: Overall, we found that only 3/30 (10%) of TNBC patients had TILs >50%. In addition, 14/30 (46.7%) of TNBC patients had tumors with 10% v. Conclusions: Only 10% of TNBC patients enrolled in the study had LPBC at diagnosis thus indicating that this cohort was not enriched for patients with immunogenic tumors. When stratified by TILs >10% or Citation Format: Rybstein MD, Nackos E, Kornhauser N, Cigler T, Andreopoulou E, Moore A, Cobham M, Fitzpatrick V, Demaria S, Vahdat LT. Tumor infiltrating lymphocytes (TILS) among high risk for recurrence breast cancer patients treated with tetrathimolybdate (TM) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-10.

Background: Metals have emerged as a viable therapeutic target for a new generation of anti-cancer and anti-metastatic agents. Copper, an essential trace element, serves as an important catalytic cofactor in several biological functions and has emerged as an essential factor in carcinogenesis. Among other elements, bone marrow derived VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent lysyl oxidase (LOX) are key elements in tumor progression. We hypothesized tetrathiomolybdate (TM)-associated copper depletion (CD) inhibits tumor metastases by reducing the number of EPCs and other copper dependent processes in the pre-metastatic niche. These results are an update of our previously reported study (Chan N, Willis A, Kornhauser N et al. Influencing the Tumor Microenvironment: Phase 2 Study of Copper Depletion with Tetrathiomolybdate in High Risk Breast Cancer and Preclinical Models of Lung Metastases. Clin Cancer Res. October 21, 2016) with longer follow-up. Methods: A single arm phase II study of breast cancer (BC) patients (pts) at high risk for recurrence, defined as node+ triple negative (TNBC), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. TM was given to maintain ceruloplasmin (Cp) levels between 8-16 mg/dl for two years with an extension phase or until relapse. The primary endpoint was a change in EPCs measured by flow cytometry before and during treatment. Secondary endpoints included tolerability, safety, PFS and LOXL-2 levels. Results: Seventy-five pts received 2778 cycles of TM on the primary and extension study. The primary study treatment duration was 24 cycles (each cycle is 28 days) plus an extension phase. The median age is 51 years (range 29-66). Forty-five pts have stage 2/3 BC and 30 with stage 4 NED. Forty-eight percent of pts are TNBC and 40% of pts are stage 4 NED. Median Cp levels were monitored with each cycle. A decrease from 28 to 16 (p Conclusions: TM is safe, well tolerated and appears to affect multiple components of the tumor microenvironment that have been identified in pre-clinical models as important for progression. Ongoing studies in banked specimens are underway to further delineate its effect on copper dependent processes necessary for metastases. Randomized trials are warranted, especially in patients who are at high risk for relapse such as those with TNBC. Citation Format: Sahota S, Willis A, Kornhauser N, Ward M, Cobham M, Cigler T, Moore A, Andreopoulou E, Fitzpatrick V, Schneider S, Prima N, Wiener A, Ko D, De Laurentiis A, Warren JD, Rubinchik A, Mittal V, Vahdat LT. A phase II study of copper-depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence: Updated results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-02.

Purpose: To describe demographic factors and calculate prevalence of heart disease–related conditions among the adult Down syndrome (DS) sample population and to compare demographic and heart disease–related conditions between the DS sample population (n = 2342) and the general population. Methods: Using a retrospective, descriptive cohort study design, analyses were based on 20 years of data collected on the Adult Down Syndrome Center patient population. Prevalence of heart disease, stroke, and associated risk conditions are reported as counts (%) with corresponding odds ratio (OR) indicating odds of diagnosis among the DS sample compared with the general population. Corresponding Pearson c2P-values were calculated to represent statistically significant differences between prevalence of diagnoses in the DS sample compared with the general population. In cases where prevalence was low, Fisher’s Exact Test P-value were calculated. Results: Adults with DS had lower odds of diagnosis of heart disease and most associated risk conditions, specifically coronary heart disease (OR = 0.0537, P Conclusion: Adults with DS generally experience less heart disease and associated risk conditions commonly seen in the general population. Prevention and treatment guidelines for heart disease for the DS population should be adjusted after more research is conducted.

In addition to a number of micro-convergences, this issue’s essays overwhelmingly evidence a shared project of contextualization. This common spirit emerges in the imperative to historicize, aimed ...

Background Studies show that patients want to engage in cost-of-care conversations and factor costs into the formulation of care plans. Low-income patients are particularly likely to defer care because of costs, suggesting that cost-of-care conversations may be an important factor in health equity. Little guidance is available to clinicians and health systems for how to integrate effective cost-of-care conversations into clinical practice or to address specific cost needs of low-income patients. Objective To develop a framework and tool to assist cost-of-care conversations with low-income patients during prenatal care. Design A qualitative study using human-centered design methods. Setting University medical center-based obstetrics-gynecology (ob-gyn) practice. Participants 20 pregnant or recently postpartum women, 16 clinicians, and 8 support and executive staff. Results Pregnant women accumulate substantial indirect costs that interfere with treatment adherence and stress patients and their relationships. Frequency and duration of appointments are primary drivers of indirect costs; the burden is exacerbated by not knowing these costs in advance and disproportionately affects low-income patients. Working with ob-gyn clinicians, staff, and patients, a paper-based tool was developed to help patients forecast treatment demands and indirect costs, and to help clinicians introduce and standardize cost conversations. Limitations Data were collected from a small number of stakeholders in a single clinical setting that may not be generalizable to other settings. The tool has not been tested for effects on adherence or clinical outcomes. Conclusion A communication tool that helps pregnant patients understand their care plan and anticipate indirect costs can promote cost-of-care conversations between clinicians and low-income patients. Primary funding source Robert Wood Johnson Foundation.

Background: Copper is an important catalytic cofactor in several biological functions and is essential for lysyl oxidase (LOX), a key enzyme in cross-linking collagen, which may play a role in tumor metastasis. We hypothesized that tetrathiomolybdate (TM)-associated copper depletion (CD) would inhibit tumor metastases by altering copper dependent collagen remodeling in the pre-metastatic niche. These results are an update of our previously reported clinical outcomes with longer follow-up and translational outcomes implicating the tumor microenvironment in metastatic transformation of BC. Methods: Pts at high risk for recurrence, node+ triple negative (TNBC) or stage 3/4 BC with no evidence of disease (NED), were enrolled on a phase II study of CD with TM. TM was given to maintain ceruloplasmin (Cp) levels between 8-16 mg/dl for two years (yrs) with an extension phase or until relapse. Median Cp levels were monitored with each cycle. Clinical endpoints included safety/tolerability and progression of disease (POD)/death. Event-free (EFS) and overall survival (OS) were calculated using Kaplan Meier survival analyses. Translational endpoints included markers of collagen cross-linking (LOXL-2), formation (PRO-C3), and degradation (C1M and C6M). Results: Seventy-five pts received 2993 cycles of TM on the primary (24 cycles, 28 days per cycle) and extension study. Median age was 51 yrs (range 29-66). Forty-five pts had stage 2/3 BC, and 30 pts were stage 4 NED. At a median follow-up of 8.4 yrs, the overall EFS was 71.4% and OS was 78.8%. The EFS and OS for the 36 pts with TNBC were 71.7% and 81%, and the EFS and OS for the 39 pts with Luminal/HER2+ BC were 71.2% and 78.6% respectively. TM was well tolerated with grade 3/4 toxicities including: neutropenia (1.9%), febrile neutropenia (0.03%), and fatigue (0.2%). LOXL2 levels were significantly decreased at 12 and 24 cycles compared with baseline (p Citation Format: Liu YL, Bager CL, Willumsen N, Kornhauser N, Cobham M, Andreopoulou E, Cigler T, Moore A, LaPolla D, Fitzpatrick V, Ward M, Warren JD, Mittal V, Vahdat LT. A phase II study of copper-depletion using tetrathiomolybdate (TM) in patients (pts) with high risk breast cancer (BC): Role of collagen processing and tumor microenvironment [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 PD9-07.

Purpose: Bone marrow–derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models. Experimental Design: Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition. Results: Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II–III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012). Conclusions: Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted.

2557 Background: The tumor microenvironment (TME) plays a critical role in the spread of tumors. Bone marrow derived VEGFR2+endothelial progenitor cells (EPCs) and copper-dependent lysyl oxidase (LOX) are key in tumor progression. We hypothesized TM-associated copper depletion inhibits tumor metastases by reducing the number of EPCs and other copper dependent (CD) processes in the pre-metastatic niche. These results are an update with longer follow-up. Methods: Phase II study of BC pts at high risk for recurrence, defined as node+ triple negative (TNBC), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. Ceruloplasmin (Cp) levels were maintained between 8-16 mg/dl for two years with an extension phase or until relapse. The primary endpoint was change in EPCs measured by flow cytometry before and during treatment. Secondary endpoints included tolerability, safety, PFS and LOXL-2 levels. Results: 75 pts received 2650 cycles of TM on primary and extension study. The median age is 51 years (range 29-66). Forty-five pts have stage 2/3 BC and 30 with stage 4 NED. TNBC pts were 48% and 40% of pts are stage 4 NED. Median Cp level decreased from 28 to 16 (p < 0.0001) after one cycle. Copper depletion was most efficient in TNBC where Cp levels dropped from 23.5 to 13 after one cycle. TM was well tolerated with grade 3/4 toxicities including: reversible neutropenia (2.3%), febrile neutropenia (0.04%), fatigue (0.2%). Five-year analysis showed a decrease in EPC’s (p = 0.004) and LOXL-2 (p < 0.001). At a median follow-up of 6.9 years, the EFS for 75 pts is 75.6%. PFS for 36 pts with TNBC is 79.2%. EFS for stage 2/3 TNBC is 90% and for stage IV TNBC is 66.7%. Conclusions: TM is safe, well tolerated and appears to affect multiple components of the TME creating an inhospitable environment for tumor progression especially in high risk patients such as TNBC. Randomized trials are warranted, especially in patients at high risk for relapse. Clinical trial information: UL1TR000457.

Background: The pre-metastatic niche mobilizes copper to assist in conditioning the tumor microenvironment facilitating tumor progression. This includes bone marrow derived VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent lysyl oxidase (LOX). We hypothesized that TM-associated CD would reduce EPCs and other copper dependent processes in the pre-metastatic niche in BC pts. Methods: Stage 2 triple negative BC, Stage 3 and stage 4 without any evidence of disease, (NED) BC pts, received oral TM to maintain ceruloplasmin (Cp) between 8-17mg/dL for 2 years or until relapse. Endpoints included change in EPCs, safety, disease-free (DFS) and overall survival (OS) and effect on biomarkers. Laboratory studies: MDA-LM2-luciferase cells were implanted into CB17-SCID mice, and treated with TM or water. Tumor progression was quantified by bioluminescence imaging (BLI), CD status by Cp oxidase levels, lysyl oxidase (LOXL2) activity by ELISA, and collagen deposition by Picrosirius Red staining and Second Harmonic Generation (SHG) imaging analysis. Results: 75 pts (45 stage 2/3 BC, 30 stage 4 NED) received over 2400 cycles of TM on the primary and extension studies. Median age: 51 yrs (range 29-66). Of the 75 pts, 48% had TNBC, 40% were stage 4 NED. Median Cp level decreased from 28 at baseline to 15.5 (p Conclusions: TM is safe, well tolerated and appears to affect multiple copper dependent biologic processes in the tumor microenvironment known to be important for tumor progression, most striking in TNBC. Randomized trials in a high risk for relapse population are warranted. Citation Format: Eleni Nackos, Sharrell Lee, Amy Willis, Naomi Kornhauser, Maureen Ward, Marta Cobham, Tessa Cigler, Anne Moore, Veronica Fitzpatrick, Sarah Schneider, Alysia Wiener, Jessica Guillaume-Abraham, Bo Ri Seo, J David Warren, Anna Rubinchik, Claudia Fischbach, Vivek Mittal, Linda Vahdat. Copper depletion as a strategy to affect the tumor microenvironment in breast cancer patients at high risk of relapse and in triple negative preclinical models of breast cancer: Updated results of a phase II study of tetrathiomolybdate (TM) in breast cancer (BC) patients (pts) at high risk for recurrence. [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 LB-349.

11008 Background: Bone marrow derived endothelial progenitor cells (EPCs) and copper-dependent pathways are critical components to remodeling the tumor microenvironment and creating the pre-metasta...