The Integration of Value Assessment and Social Network Methods for Breast Health Navigation Among African Americans.

OBJECTIVES: A major strategy to reduce the impact of breast cancer (BC) among African Americans (AA) is patient navigation, defined here as individualized assistance for reducing barriers to healthcare use. The primary focus of this study was to estimate the added value of incorporating breast health promotion by navigated participants and the subsequent BC screenings that network members may obtain. METHODS: In this study, we compared the cost-effectiveness of navigation across 2 scenarios. First, we examine the effect of navigation on AA participants (scenario 1). Second, we examine the effect of navigation on AA participants and their networks (scenario 2). We leverage data from multiple studies in South Chicago. Our primary outcome (BC screening) is intermediate, given limited available quantitative data on the long-term benefits of BC screening for AA populations. RESULTS: When considering participant effects alone (scenario 1), the incremental cost-effectiveness ratio was $3845 per additional screening mammogram. When including participant and network effects (scenario 2), the incremental cost-effectiveness ratio was $1098 per additional screening mammogram. CONCLUSION: Our findings suggest that inclusion of network effects can contribute to a more precise, comprehensive assessment of interventions for underserved communities.

Characteristics of patients with hematologic malignancies without seroconversion post-COVID-19 third vaccine dosing.

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.

Real-World Third COVID-19 Vaccine Dosing and Antibody Response in Patients With Hematologic Malignancies.

Purpose: This study sought to describe the changes in immune response to a third dose of either Pfizer's or Moderna's COVID-19 mRNA vaccine (3V) among patients with hematologic malignancies, as well as associated characteristics. Methods: This retrospective cohort study analyzed pre-3V and post-3V data on 493 patients diagnosed with hematologic malignancies across a large Midwestern health system between August 28, 2021, and November 1, 2021. For antibody testing, S1 spike antigen of the SARS-CoV-2 virus titer was used to determine serostatus. Results: Among 493 participants, 274 (55.6%) were seropositive both pre- and post-3V (+/+) while 115 (23.3%) seroconverted to positive from prior negative following the third dose (-/+). The remaining 104 (21.1%) were seronegative both before and after 3V (-/-). No participant was seropositive pre-3V and seronegative post-3V (+/-). Results showed a statistically significant increase in the proportion of seropositivity after receiving a third COVID-19 vaccine (P<0.00001). Response to 3V was significantly associated with the 3V vaccine type (P=0.0006), previous COVID-19 infection (P=0.0453), and malignancy diagnosis (P<0.0001). Likelihood of seroconversion (-/+) after 3V was higher in the group of patients with multiple myeloma or related disorders compared to patients with lymphoid leukemias (odds ratio: 8.22, 95% CI: 2.12-31.79; P=0.0008). Conclusions: A third COVID-19 vaccination is effective in producing measurable seroconversion in many patients with hematologic malignancies. Oncologists should actively encourage all their patients, especially those with multiple myeloma, to receive a 3V, given the high likelihood of seroconversion.

Prevalence of Infectious Diseases Among 6078 Individuals With Down Syndrome in the United States.

A recent disease prevalence study of the largest documented Down syndrome (DS) cohort in the United States strongly suggested significant disparity in general infectious disease conditions among individuals with DS versus those without DS. In this follow-up retrospective analysis, we explored these differences in greater detail by calculating prevalence of 52 infectious diseases, across 28 years of data among 6078 individuals with DS and 30,326 age- and sex-matched controls, abstracted from electronic medical records within a large Midwestern health system. We found that the DS cohort had higher prevalence of pneumonias (including aspiration, viral, bacterial, pneumococcal, and unspecified/atypical); otitis externa; and the skin infections impetigo, abscess, and cellulitis. To the contrary, the DS cohort had lower prevalence of many respiratory infections other than pneumonia (including influenza, strep pharyngitis, upper respiratory infection, sinusitis, tonsillitis, laryngitis, bronchitis, scarlet fever, and otitis media); sexually transmitted infections (including bacterial vaginosis, chlamydia, genital herpes, HIV/AIDS, human papillomavirus, pelvic inflammatory disease, and trichomoniasis); mononucleosis; shingles; unspecified hepatitis; intestinal infections; and enteritis. These findings highlight that individuals with DS could be more or less prone to different infectious diseases than their non-DS matched counterparts. Additional research to understand why these differences exist and how they might affect the clinical approach to patients with DS is warranted.

Prevalence of Endocrine Disorders Among 6078 Individuals With Down Syndrome in the United States.

Findings from a recent study describing prevalence of common disease conditions in the largest documented cohort of individuals with Down syndrome (DS) in the United States strongly suggested significant disparity in endocrine disorders among these individuals when compared with age- and sex-matched individuals without DS. This retrospective, descriptive study is a follow-up report documenting prevalence of 21 endocrine disorder conditions, across 28 years of data, from 6078 individuals with DS and 30,326 age- and sex-matched controls, abstracted from electronic medical records within a large integrated health system. Overall, individuals with DS experienced higher prevalence of adrenal insufficiency and Addison's disease; thyroid disorders, including hypothyroidism, hyperthyroidism, Hashimoto's disease, and Graves' disease; prolactinoma/hyperprolactinemia; diabetes insipidus; type I diabetes mellitus; and gout. Conversely, those with DS had lower prevalence of polycystic ovary syndrome and type II diabetes mellitus. Many prevalences of endocrine conditions seen in individuals with DS significantly differ relative to their non-DS matched counterparts. These varied findings warrant further exploration into how screening for and treatment of endocrine conditions may need to be approached differently for individuals with DS.

Navigated African American breast cancer patients as incidental change agents in their family/friend networks.

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.

Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer.

Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls. We measured these collagen biomarkers in TM-treated patients on the phase II study and detected evidence of decreased collagen cross-linking and increased degradation over formation in those without disease compared to those who experienced disease progression. Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls. This study reveals novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.

Prevalence of Common Disease Conditions in a Large Cohort of Individuals With Down Syndrome in the United States.

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.

Understanding the relationship between positive and negative social support and the quality of life among African American breast cancer survivors.

PURPOSE: Social support improves several quality of life (QOL) domains among African American breast cancer survivors. How different dimensions of social support are associated with QOL among African American breast cancer survivors may however 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 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) were 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 ß=1.60, CI: 0.51, 2.69, p= 0.004) and imputed models (Std ß= 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 ß=-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.

Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases.

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. Clin Cancer Res; 23(3); 666-76. ©2016 AACR.