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Introduction: This study evaluated the relationships between patient and cancer delivery factors with trust in oncology providers in a racial/ethnically diverse group of cancer patients., Methods: Data were analyzed from a prospective cohort study of women with hormone receptor positive (HR+) breast cancer. A standardized survey collected validated measures of trust in providers, psychosocial factors, and cancer care delivery factors. Multivariable logistic regression models and race-stratified models were employed to calculate odds ratios and 95% confidence intervals associated with trust., Results: Of the 567 participants, 28% identified as Black and the rest were White. Compared to White women Black women reported lower trust in providers. Four domains of cancer care delivery were significantly associated with patients' higher trust in their providers: general satisfaction with care (P < .0001), technical quality of the provider (P < .001), interpersonal manner of the provider (P = .0008) and provider communication (P = .0010). Race-stratified models revealed 2 significant cancer care delivery domains for both groups (ie, general satisfaction and interpersonal) and 2 care domains (technical quality and communication) that were only significant among White women., Conclusion: Efforts are needed to nurture trusting relationships between Black women and their oncology providers. Factors related to the organization and delivery of cancer care are modifiable targets for interventions as these were robust predictors of patient trust regardless of a woman's self-reported race. Investments in strategies that strengthen the structure and organization of care towards a structures of trust worthiness may better support providers and patients and ultimately reduce cancer care disparities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

•Situating engagement within the experience and priorities of survivors will enhance translational research and health equity.•The TRUST framework provides a guide to expand opportunities for community engagement in cardio-oncology for multiple constituents and across the care continuum.•Training community members as cardio-oncology champions may promote stakeholder representation.•Community connectors can support bidirectional engagement and support for survivors as they transition from active treatment., Competing Interests: Dr Sheppard is supported by the National Cancer Institute, Community Outreach and Engagement (PI: P30CA016059); the American Cancer Society (RSG-19-182-01-CPPB), which focuses on “Improving Communication and Adherence in Black Breast Cancer Survivors”; and the NCI Community Oncology Research Program (NCORP) (UG1CA189869), which is focused on the “VCU Massey Minority/Underserved NCI Community Oncology Research Program.” Dr Sutton is supported by the National Cancer Institute (R00CA256038). Dr Guha is supported by the American Heart Association-Strategically Focused Research Network Grant in Disparities in Cardio-Oncology (#847740, #863620) and the Department of Defense Prostate Cancer Research Program’s Physician Research Award (#HT94252310158). None of these funds supported this work. Dr Guha has an academic consulting relationship with Pfizer and Novartis; and his institution has received research funding from Sumitomo Pharma; however, there is no conflict of interest in submitting this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Purpose: Black women are more likely than White women to have obesity, and obesity is associated with worse breast cancer prognosis. Weight perception, however, has not been studied as a potential mediator of obesity disparities in women with breast cancer. In this study, we sought to describe racial differences and the association of lifestyle factors with weight perception., Methods: In this cross-sectional study design, Black and White women with a new primary breast cancer were surveyed about socio-demographics, weight perception, diet, and exercise habits. Height and weight were measured at enrollment. We classified women with a BMI ≥ 25 kg/m 2 or waist circumference ≥ 88 cm who reported that they were "about the right weight" as under-perceivers. Chi-square and t tests were used to assess study variables (e.g., race, physical activity) associated with under-perception of weight. Logistic regression models were fit to evaluate for racial differences in under-perception while controlling for other covariates., Results: Of 1,197 women with newly diagnosed breast cancer, the average age was 58 years, and 909 (75.9%) were White. Nine hundred eighteen (77%) had stage I cancer, 1,035 (87%) had estrogen receptor positive cancer, and 795 (66%) were privately insured at time of diagnosis. Seven hundred eighty-nine (66%) women had abdominal obesity (waist circumference ≥ 88 cm), while 366 (31%) women had a BMI ≥ 25 kg/m 2 . Overall, 24% of women were under-perceivers. Compared to White women, Black women with WC ≥ 88 cm more frequently under-perceived their weight (24% vs. 14% p < 0.0001) were more obese with BMI > 30 kg/m 2 (51% vs. 23%, p < 0.0001) and had lower physical activity (22% vs. 77%, p < 0.0001). After controlling for age, education, and stage, Black women remained more likely to under-perceive their weight relative to White women for those with BMI ≥ 25 kg/m 2 (OR: 2.64; 95% CI: 1.4-4.6) or waist circumference ≥ 88 cm (OR: 2.89; 95% CI: 1.8-4.5). With respect to lifestyle factors, among women with BMI ≥ 25 kg/m 2 , those who met physical activity guidelines were less likely to under-perceive their weight compared to those who did not meet physical activity guidelines (OR: 0.37; 95% CI: 0.2-0.6), regardless of race., Conclusions: We found racial differences in weight perception and identified social determinants and lifestyle factors such as lower education and physical inactivity that influenced under-perception of weight among newly diagnosed breast cancer patients., Implications for Cancer Survivors: Since obesity is associated with worse breast cancer outcomes, identifying optimal modifiable factors to intervene upon to support weight management among breast cancer survivors is clinically important. Breast cancer patients' perceptions about their weight provide insight that may inform lifestyle behavior interventions to reduce obesity during survivorship care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We examined whether there are racial disparities in pain management, opioid medicine prescriptions, symptom severity, and quality of life constructs in breast cancer survivors., Methods: We conducted a secondary analysis of longitudinal data from the Women's Hormonal Therapy Initiation and Persistence (WHIP) study (n = 595), a longitudinal study of hormonal receptor-positive breast cancer survivors. Upon study enrollment, patients completed a survey assessing an array of psychological, behavioral, and treatment outcomes, including adjuvant endocrine therapy (AET)-induced symptoms, and provided a saliva biospecimen. Opioid prescription records were extracted from the health maintenance organizations (HMOs) pharmacy database. The final analytic sample included women with complete HMO pharmacy records for 1 year., Results: There were 251 eligible patients, of which 169 (67.3%) were White. The average age was 61.09 years old (SD = 11.07). One hundred seventy-two patients (68.5%) had received at least one opioid medication and 37.1% were prescribed opioids longer than 90 days (n = 93). Sixty-four Black patients (78%) had a record of being prescribed with opioids compared to 64% of White patients (n = 108, p = 0.03). Black patients reported worse vasomotor, neuropsychological, and gastrointestinal symptoms, as well as lower quality of life and greater healthcare discrimination than White patients (p's < 0.05). Black patients were more likely to be prescribed opioids for 90 days or longer compared to White patients, when controlling for age, marital status, income, body mass index (BMI), cancer stage, and chemotherapy status (adjusted Odds Ratio = 2.72, p = 0.014)., Conclusion: Findings indicate that there are racial differences in opioid prescriptions supplied for pain management and symptomatic outcomes. Future research is needed to understand the causes of disparities in cancer pain management and symptomatic outcomes., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Surveillance mammography is recommended annually for early detection of disease relapse among breast cancer survivors; yet Black women have poorer national rates of surveillance mammography compared to White women. Factors that influence racial disparities in surveillance mammography rates are poorly understood. The purpose of this study is to evaluate the contribution of health care access, socioeconomic status, and perceived health status on adherence to surveillance mammography among breast cancer survivors., Methods: This is a secondary analysis of a cross-sectional survey among Black and White women ≥ 18 years, who reported a breast cancer diagnosis and completed breast surgery and adjuvant treatment from the 2016 Behavioral Risk Factor Surveillance System National Survey (BRFSS). Bivariate associations (chi-squared, t-test) for independent variables (e.g., health insurance, marital status) were analyzed with adherence to nationally recommended surveillance guidelines defined as two levels: adherent (received a mammogram in the last 12 months), vs. non- adherent ("received a mammogram in the last 2-5 years, 5 or more years or unsure). Multivariable logistic regression models were used to evaluate the relationship between study variables with adherence, while adjusting for potential confounders., Results: Of 963 breast cancer survivors, 91.7% were White women with an average age of 65. 71.7% reported a surveillance mammogram in the last 12 months, while 28.2% did not. Diagnosed > 5 years (p < 0.001); not having a routine checkup visit within 12 months (p = 0.045); and not seeing a doctor when needed due to cost (p = 0.026), were significantly related to survivor's non-adherence to surveillance mammography guidelines. A significant interaction was found between race and residential area (p < 0.001). Compared to White women, Black women living in metropolitan/suburban residential areas were more likely to receive surveillance guidelines (OR:3.77;95% CI: 1.32-10.81); however Black women living in non-metropolitan areas were less likely to receive a surveillance mammogram compared to White women living in non-metropolitan areas (OR: 0.04; 95% CI: 0.00-0.50)., Conclusion: Findings from our study further explain the impact of socioeconomic disparities on racial differences in the use of surveillance mammography among breast cancer survivors. Black women living in non-metropolitan counties are an important subgroup for future research and screening and navigation interventions., (© 2023. The Author(s).)

Purpose: Social support is associated with breast cancer survivors' health-related quality of life (HRQoL). More nuanced information is needed regarding aspects of social support associated with different HRQoL domains among diverse populations. We assessed the association between emotional/informational and tangible support and five HRQoL domains and evaluated race as an effect modifier., Methods: African American and White women (n = 545) diagnosed with hormone-receptor-positive breast cancer completed a survey that assessed sociodemographic, clinical, and psychosocial factors. We assessed bivariate relationships between emotional/informational and tangible support along with overall HRQoL and each HRQoL domain.We tested interactions between race and emotional/informational and tangible social support using linear regression., Results: The sample included African American (29%) and White (71%) breast cancer survivors. Emotional/informational social support had a statistically significant positive association with emotional well-being (β = .08, p = 0.005), social well-being (β = 0.36, p < 0.001), functional well-being (β = .22, p < .001), breast cancer concerns (β = .16, p = 0.002), and overall HRQoL (β = .83, p < .001). Similarly, tangible social support had a statistically significant positive association with emotional well-being (β = .14, p = 0.004), social well-being (β = .51, p < .001), functional well-being (β = .39, p < .001), and overall HRQoL (β = 1.27, p < .001). The interactions between race and social support were not statistically significant (p > 0.05)., Conclusions: Results underscore the importance of the different social support types among breast cancer survivors, regardless of survivors' race., Implications for Cancer Survivors: Population-based interventions can be standardized and disseminated to provide guidance on how to increase emotional/information and tangible support for all breast cancer survivors by caregivers, health providers, and communities., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The use of surveillance mammography following a breast cancer (BC) diagnosis is associated with early detection of disease relapse and increased overall survival; yet Black women compared to White women have the lowest surveillance mammography rates, with limited explanation. To further understand this racial disparity the present study examines the association of mammography beliefs, knowledge, and healthcare delivery factors on receipt of surveillance mammography among Black and White breast cancer survivors., Methods: This is a convergent parallel mixed method study design of an online survey and online focus groups among Black and White BC survivors (N = 266) recruited from community engagement. The online focus groups consisted of a series of theory-informed questions via social media platforms (eg Breastcancer.org, Quora, Reddit). An in-depth thematic analysis approach was used to extract themes from online focus group data. Bivariate (χ 2 ) and multivariable logistic regression analyses were conducted using the survey data to examine associated factors with receipt of a surveillance mammography within 12 months (yes vs. no)., Results: 76% (n = 177) of women were Black, 62% were <5 years since diagnosis, 98% had health insurance, with an age range from 23 to 79 (mean = 55) years. 72% of the sample received a surveillance mammogram relative to 27%. Women more frequently received a surveillance mammogram if they reported perceived mammography benefits (<.001), underwent lumpectomy (P< .001) and had health insurance (P = .04). Black women without communication about surveillance care with providers had a lower likelihood of receiving a surveillance mammogram (OR:0.09,95% CI: 0.01-0.45, P = .003). Thematic findings from online focus groups included motivators for receipt of surveillance mammograms: physician recommendation, regular physical exams, and knowledge of recommended guidelines. Barriers of non-receipt of surveillance mammograms included: transportation, medical cost/financial barriers, feeling ignored from providers, and medical mistrust., Conclusion: Women may require more individualized information regarding their surveillance care to support routine guideline concordant follow-up. Patient-provider-communication is an integral part of Black survivors' surveillance care needs. Improving patient-provider communication for Black women's is necessary to address this group cancer care needs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Breast cancer beliefs are widely studied to improve preventative screening behaviors in women without cancer; however, limited research has examined breast cancer beliefs among breast cancer survivors. To fill this gap in research we investigated racial differences and the predicting role of influential factors (e.g., stage) in survivors' beliefs about their breast cancer., Methods: This study is a secondary analysis of data from the Narrowing Gap in Adjuvant Therapy Study (2006-2011), where Black (N = 210) and White women (N = 149) were interviewed within 20 weeks following their breast cancer diagnosis and primary surgery in Washington DC and Detroit, MI. Outcomes of this analysis were perceived susceptibility to a breast cancer recurrence and perceived severity of breast cancer. Bivariate analyses were conducted to assess racial differences in sample characteristics, and on the study outcomes. Adjusted multiple regression models examined correlates between independent variables (e.g., sociodemographic/clinical) and women's breast cancer beliefs about susceptibility of a recurrence and disease severity., Results: Most of the sample were Black women (58%), had breast-conserving surgery (64%), and were privately insured (67%). Black women reported higher perceived disease severity beliefs than White women (p = 0.004). Other associated factors with greater perceived severity beliefs included lower education (p = 0.008), public health insurance (p = 0.021) and greater levels of medical mistrust (p = 0.016). In our adjusted multiple regression models' women with lower satisfaction regarding financial aspects of their healthcare were more likely to have higher perceived severity beliefs (p = 0.007); women with stage II cancer compared to stage I had greater susceptibility beliefs to a cancer recurrence (p = 0.001)., Conclusion: We found racial differences in women's perceived severity beliefs, and identified theory-based clinical and psychosocial correlates in survivor's breast cancer beliefs by race. Specifically, women diagnosed at stage (II) compared to stage (I) reported greater perceived susceptibility to a recurrence. Survivors diagnosed at stage (I) and (III) cancers may serve as important target groups to monitor their surveillance and follow-up behaviors. This study contributes salient predictors in survivors' beliefs about their BC and informs navigation strategies to improve cancer survivorship recommendations in the context of psycho-oncology and follow-up cancer care., (© 2022 John Wiley & Sons Ltd.)

Objective: Inclusion of women in biomedical cancer research have the potential to close gaps in cancer health disparities and improve adjuvant therapies for women; yet samples needed to advance this area of science are lacking. We developed low-cost educational recruitment strategies to increase our collection of biospecimens from women. Materials and Methods: Women diagnosed with hormone receptor positive (HR+) breast cancer that initiated hormonal therapy were recruited from three integrated health systems. The analytical sample ( n  = 144) consisted of women who consented but did not return a saliva sample within 1 year of the initial assessment (baseline). Brief informational recruitment materials were developed via published literature and preliminary data. Women received recruitment materials, which included a personalized information letter, a colorful low-literacy instruction sheet, a postage-paid envelope, and collection kits. We evaluated intervention materials and performed descriptive and bivariate statistics to describe factors associated with biospecimen donation. Results: Of the total sample, 61% were white and 34% were black. Overall, 29 surveys (20%) and 25 (17%) saliva kits were returned. Women found the materials helpful and easy to read and understand. Women with higher levels of functional well-being and lower ratings of religiosity were more likely to return biospecimens ( p  < 0.005) after receiving enhanced materials. Conclusion: This article provides recruitment strategies to enhance biospecimen samples among women. Receipt of brief informational print materials inclusive of personalized messages enhanced our outreach strategies and increased our overall biospecimen provision rate by 17%. The inclusion of messages with a focus on spirituality and other cultural messages may further increase biospecimen provision in racial/ethnic diverse groups of women; however, further study is needed to support this claim. Clinical Trail Registration Number: NCT02992730.

Background: Adjuvant endocrine therapy (AET) improves outcomes in women with hormone receptor-positive (HR + ) breast cancer. Suboptimal AET adherence is common, but data are lacking about symptoms and adherence in racial/ethnic minorities. We evaluated adherence by race and the relationship between symptoms and adherence., Methods: The Women's Hormonal Initiation and Persistence study included women diagnosed with nonrecurrent HR + breast cancer who initiated AET. AET adherence was captured using validated items. Data regarding patient (e.g., race), medication-related (e.g., symptoms), cancer care delivery (e.g., communication), and clinicopathologic factors (e.g., chemotherapy) were collected via surveys and medical charts. Multivariable logistic regression models were employed to calculate odds ratios and 95% confidence intervals (CIs) associated with adherence., Results: Of the 570 participants, 92% were privately insured and nearly one of three were Black. Thirty-six percent reported nonadherent behaviors. In multivariable analysis, women less likely to report adherent behaviors were Black (vs. White; OR, 0.43; 95% CI, 0.27-0.67; P < 0.001) and with greater symptom burden (OR, 0.98; 95% CI, 0.96-1.00; P < 0.05). Participants more likely to be adherent were overweight (vs. normal weight) (OR, 1.58; 95% CI, 1.04-2.43; P < 0.05), sat ≤ 6 hours a day (vs. ≥6 hours; OR, 1.83; 95% CI, 1.25-2.70; P < 0.01), and were taking aromatase inhibitors (vs. tamoxifen; OR, 1.91; 95% CI, 1.28-2.87; P < 0.01)., Conclusions: Racial differences in AET adherence were observed. Longitudinal assessments of symptom burden are needed to better understand this dynamic process and factors that may explain differences in survivor subgroups., Impact: Future interventions should prioritize Black survivors and women with greater symptom burden., (©2021 American Association for Cancer Research.)

Purpose: Black breast cancer patients delay and underutilize adjuvant breast cancer therapies; yet, very few studies have specifically examined Black women's attitudes toward breast cancer therapy. This study observed the influence of self-reported interpersonal processes of care (e.g. self-efficacy) clinical and sociodemographic factors and sociocultural (e.g. religiosity), related to Black breast cancer patients' attitudes toward radiation and systemic therapies (chemotherapy and adjuvant endocrine therapy - "AET")., Methods: This was a secondary analysis of data from the Narrowing Gaps in Adjuvant Therapy Study (2006-2011). The analysis included 210 Black women who were newly diagnosed with breast cancer. Bivariate and multiple regression analyses were performed between independent variables (e.g., demographics) and three outcome variables (chemotherapy, AET, and radiation therapy) to asses women's perceptions of therapy type. The lasso method was used to select variables correlated with therapy attitudes., Results: Most women reported negative attitudes toward AET (56%) and radiation (54%); fewer negative attitudes were observed toward chemotherapy (47%). Higher education and greater perceived susceptibility of a recurrence were associated with more positive attitudes toward chemotherapy. Regarding radiation therapy, women with greater patient satisfaction were more likely to have more positive attitudes., Conclusions: Our study findings may aid in the development of behavioral interventions targeted to mitigate Black women breast cancer treatment disparities. We found modifiable factors (e.g. communication, satisfaction ratings) that support opportunities for clinicians to better address Black women's needs regarding adjuvant treatment options. The development of tailored interventions for newly diagnosed Black breast cancer patients on patient related factors in health care are warranted for Black women with lower educational levels., (Published by Elsevier Inc.)

The benefits of genetic counseling and testing for hereditary breast and/or ovarian cancer (HBOC) are well documented; however, Black women are less likely to use these services compared to White women. Mistrust of the medical system has been associated with Black women's use of genetic counseling and testing (GCT). However, relatively little is known about the correlates of medical mistrust in Black women at increased risk of HBOC. In this study, we examined the prevalence and predictors of medical mistrust in 94 Black women at-risk of HBOC. Most women were married (48.7%) and had at least some collegiate education (57.1%). While no predisposing characteristics were significantly related to medical mistrust, bivariate analysis indicated significant relationships between mistrust and fatalism (p=0.04), perceptions of discrimination in the healthcare setting (p=0.01), and self-efficacy in obtaining GCT (p=0.01). Multivariable analysis revealed that women who reported more discriminatory experiences and women with less confidence in obtaining GCT expressed greater medical mistrust. Multilevel approaches are needed to address psychosocial factors associated with feelings of mistrust. Future efforts must not solely focus on educating women on the importance of and need for GCT; addressing structural barriers, such as patient-provider interactions, that contribute to mistrust must become a priority.

Studies indicate that Black patients report higher medical mistrust compared to their White counterparts. However, little is known about factors associated with higher medical mistrust among Black breast cancer patients. We examined predictors of medical mistrust and relationships between medical mistrust, subscales of mistrust, and process of care factors to identify opportunities to promote positive healthcare interactions between the trustees (e.g., providers) and Black breast cancer patients, or the trustors. A secondary analysis was conducted of survey data from 210 Black women with confirmed diagnosis of invasive breast cancer. Participants completed telephone surveys consisting of questions pertaining to sociodemographics, attitudes, and beliefs about medical care and breast cancer treatments. Multiple linear regression determined factors associated with medical mistrust and mistrust subscales. Most participants (61%) were over the age of 50 and currently single (64.8%). Women with greater medical mistrust reported less satisfaction with the trustee's technical ability (p < 0.0001) and greater satisfaction with their own propensity to access care (p < 0.05). Additionally, women with public insurance demonstrated greater mistrust (p < 0.01) and suspicion (p < 0.05) than women with private insurance, and women with less education reported greater perceived discrimination than women who have at least a bachelor's degree. Findings from this study may inform future endeavors to educate providers on ways to effectively interact with and treat Black breast cancer patients. Opportunities to develop interventions that address and tackle issues of mistrust as reported by Black patients may contribute to ongoing efforts to reduce health disparities.

Background: Adjuvant endocrine therapy (AET) is a critical therapy in that it improves survival in women with hormone receptor-positive (HR+) breast cancer (BC), but adherence to AET is suboptimal. The purpose of this study was to fill scientific gaps about predictors of adherence to AET among black and white women diagnosed with BC., Objective: To assess AET adherence in black and white insured women using multiple measures, including one that uses an innovative statistical approach., Methods: Black and white women newly diagnosed with HR+ BC were identified from 2 health maintenance organizations. Pharmacy records captured the type of oral AET prescriptions and all fill dates. Multivariable logistic regression was used to identify predictors of adherence defined in terms of proportion of days covered (PDC; ≥ 80%) and medication gap of ≤ 10 days. A zero-inflated negative binomial (ZINB) regression model was used to identify variables associated with the total number of days of medication gaps., Results: 1,925 women met inclusion criteria. 80% were PDC adherent (> 80%); 44% had a medication gap of ≤ 10 days; and 24% had no medication gap days. Race and age were significant in all multivariable models. Black women were less likely to be adherent based on PDC than white women (OR = 0.72, 95% CI = 0.57-0.90, P < 0.01), and they were less likely to have a medication gap of ≤ 10 days (OR = 0.65, 95% CI = 0.54-0.79, P < 0.001). Women aged 25-49 years were less likely to be PDC adherent than women aged 65-93 years (OR = 0.65, 95% CI = 0.48-0.87, P < 0.001). In the ZINB model, women were without their medication for an average of 37 days (SD = 50.5)., Conclusions: Racial disparities in adherence to AET in the study highlight a need for interventions among insured women. Using various measures of adherence may help better understand this multidimensional concept. There might be benefits from using both more common dichotomous measures (e.g., PDC) and integrating novel statistical approaches to allow tailoring adherence to patterns within a specific sample., Disclosures: This research was funded by the National Institutes of Health (R01CA154848). It was also supported in part by the NIH-NCI Cancer Center Support Grant P30 CA016059, the Laboratory of Telomere Health P30 CA51008, and the TSA Award No. UL1TR002649 from the National Center for Advancing Translational Sciences. The contents of this study are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Bosworth reports grants from Sanofi, Otsuka, Johnson & Johnson, and Blue Cross/Blue Shield of NC and consulting fees from Sanofi and Otsuka. The other authors have nothing to disclose. The datasets generated during and/or analyzed during the current study are not publicly available due to privacy reasons but are available from the corresponding author on reasonable request. The author does not own these data. Data use was granted to the author as part of a data use agreement between specific agencies and organizations.

Background: Adjuvant endocrine therapy reduces risk of recurrence and mortality in women with hormone receptor-positive breast cancer, yet many women never initiate it. We examined the influence of race, sociocultural factors, and process-of-care factors on initiation of adjuvant endocrine therapy in a racially diverse sample., Patients and Methods: Eligible women were originally recruited for the Narrowing the Gaps in Adjuvant Therapy Study (2006-2011). Sociocultural and process-of-care factors were collected via telephone surveys before adjuvant therapy. Clinical factors were abstracted from charts. Penalized LASSO (least absolute shrinkage and selection operator) logistic regression model was used to identify variables associated with initiation., Results: Of the 270 women, 55.6% were black and the rest were white. Most women (74.8%) initiated therapy. A significant interaction (P = .008) was found between race and age. Black women aged ≤ 50 years had the lowest initiation (59.7%) compared to black women > 50 years (87.1%), white women ≤ 50 years (73.7%), or white women > 50 years (72.0%). Multivariate analysis found that younger black women exhibited a marginally higher risk of noninitiation compared to older black women. Additionally, ratings of financial access, presence of comorbidities, and levels of communication were all associated with endocrine therapy initiation., Conclusion: Black women ≤ 50 years of age and women with financial constraints may be important subgroups for interventions. Patient-provider communication appears to be an important leverage point to foster therapy uptake., (Copyright © 2017 Elsevier Inc. All rights reserved.)

During early preclinical development of therapeutic proteins, representative materials are often required for process development, such as for pharmacokinetic/pharmacodynamic studies in animals, formulation design, and analytical assay development. To rapidly generate large amounts of representative materials, transient transfection is commonly used. Because of the typical low yields with transient transfection, especially in CHO cells, here we describe an alternative strategy using stable transfection pool technology. Using stable transfection pools, gram quantities of monoclonal antibody (Mab) can be generated within 2 months post-transfection. Expression levels for monoclonal antibodies can be achieved ranging from 100 mg/L to over 1000 mg/L. This methodology was successfully scaled up to a 200 L scale using disposable bioreactor technology for ease of rapid implementation. When fluorescence-activated cell sorting was implemented to enrich the transfection pools for high producers, the productivity could be improved by about three-fold. We also found that an optimal production time window exists to achieve the highest yield because the transfection pools were not stable and productivity generally decreased over length in culture. The introduction of Universal chromatin-opening elements elements into the expression vectors led to significant productivity improvement. The glycan distribution of the Mab product generated from the stable transfection pools was comparable to that from the clonal stable cell lines., (© 2010 American Institute of Chemical Engineers)

Merck Research Laboratories has developed a highly productive Escherichia coli fermentation process to produce plasmid DNA for use as vaccines. The process consists of a fed-batch fermentation in a chemically defined medium. Initiation of the feed stream precedes a growth-limited phase in which plasmid DNA is amplified. The fermentation is only maximally productive for a small fraction of E. coli transformants designated as high-producers, while the predominant low-producer population does not amplify plasmid DNA. In experiments undertaken to probe this phenomenon, transposition of the 768-bp E. coli insertion sequence IS1 into an HIV DNA vaccine vector was observed in several low-producer clones. IS1 was found to insert in or near the neomycin resistance gene in nearly a dozen unique sites from within a single population of plasmid molecules. The fraction of IS1-containing plasmids within several clones was determined by quantitative polymerase chain reaction and was found to increase with increasing cultivation time in the chemically defined medium. Because transposition into an antibiotic-resistance gene is unlikely to affect plasmid amplification, the genomes of high- and low-producers of three different HIV DNA vaccine vectors were subsequently profiled by restriction fragment length polymorphism analysis. In all three cases, IS1 insertional mutations were found in the genomes of the predominant low-producers, while the genomes of the high-producers were indistinguishable from untransformed cells. The insertions reside on similarly sized fragments for two of the low-producer clones, and the fragment size is smaller for the third clone. The third clone also produces much less plasmid DNA than a typical low-producer. The results suggest the presence of an IS1 insertional mutation that affects plasmid replication and amplification, possibly in a position-dependent manner.

To date, the FDA has approved 18 monoclonal antibody (MAb) therapeutic drugs with targets ranging from asthma and rheumatoid arthritis to leukemia. Many of these approved products are produced in Chinese hamster ovary cells (CHO) making CHO a significant and relevant host system. We studied the applicability of CHOK1SV cells as a potential host cell line for MAb production in terms of timelines, achievable titers, transfectant stability, and reproducibility. CHOK1SV, developed by Lonza Biologics, is a suspension, protein-free-adapted CHOK1-derivative utilizing the glutamine synthetase (GS) gene expression system. CHOK1SV expresses the GS enzyme endogenously; thus, positive transfectants were obtained under the dual selection of methionine sulfoximine (MSX) and glutamine-free media. We examined outgrowth efficiencies, specific productivities, and achievable batch titers of three different IgG MAbs transfected into CHOK1SV. Reducing the MSX concentration in the initial selection medium resulted in a decreased incubation time required for transfectant colonies to appear. Specific productivities of "high-producers" ranged between 11 and 49 pg/c/d with batch titers ranging from 105 to 519 mg/L. Transfectant stability and the effects of MSX also were investigated, which indicated that the addition of MSX was necessary to maintain stable MAb production. Cell growth was stable regardless of MSX concentration.