Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer

Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab

They Lift My Spirit Up: Stakeholders’ Perspectives on Support Teams for African Americans Facing Serious Illness

Active social and spiritual support for persons with cancer and other serious illnesses has been shown to improve psychological adjustment to illness and quality of life

Carrying the Burden: Perspectives of African American Pastors on Peer Support for People with Cancer

For African Americans facing advanced cancer, churches are trusted sources of support and ideal settings to improve access to supportive care. The Support Team model enhances community support for practical, emotional, and spiritual caregiving. We report on focus groups with pastors of 23 Black Churches and explore their perspective on the Support Team model for church members with cancer. Pastors describe the needs of church members facing cancer from a holistic perspective and recognize opportunities for synergistic faith-health collaboration. The results of this study indicate potential benefits of the Support Team model in Black Churches to reduce silent suffering among individuals facing cancer

Circles of Care: Development and Initial Evaluation of a Peer Support Model for African Americans With Advanced Cancer

Peer support interventions extend care and health information to underserved populations yet rarely address serious illness. Investigators from a well-defined academic–community partnership developed and evaluated a peer support intervention for African Americans facing advanced cancer. Evaluation methods used the Reach, Efficacy, Adoption, Implementation, Maintenance (RE-AIM) framework. Investigators initially recruited and trained 24 lay health advisors who shared information or support with 210 individuals. However, lay advisors reported barriers of medical privacy and lack of confidence working alone with people with cancer. Training was modified to match the support team model for peer support; training reached 193 volunteers, 104 of whom formed support teams for 47 persons with serious illness. Support teams were adopted by 23 community organizations, including 11 African American churches. Volunteers in teams felt prepared to implement many aspects of supportive care such as practical support (32%) or help with cancer or palliative care resources (43%). People with serious illness requested help with practical, emotional, spiritual, and quality of life needs; however, they rarely wanted advocacy (3%) or cancer or palliative care resources (5%) from support teams. Volunteers had difficulty limiting outreach to people with advanced cancer due to medical privacy concerns and awareness that others could benefit. Support teams are a promising model of peer support for African Americans facing advanced cancer and serious illness, with reach, adoption, and implementation superior to the lay advisor model. This formative initial evaluation provides evidence for feasibility and acceptance. Further research should examine the efficacy and potential for maintenance of this intervention

A phase 1 study of PARP-inhibitor ABT-767 in advanced solid tumors with BRCA1/2 mutations and high-grade serous ovarian, fallopian tube, or primary peritoneal cancer

Purpose This phase 1 study examined safety, pharmacokinetics (PK), and efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-767 in patients with advanced solid tumors and BRCA1/2 mutations or with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Methods Patients received ABT-767 monotherapy orally until disease progression or unacceptable toxicity. Dose was escalated from 20mg once daily to 500mg twice daily (BID). Dose-limiting toxicities, recommended phase 2 dose (RP2D), food effect, objective response rate, and biomarkers predicting response were determined. Results Ninety-three patients were treated with ABT-767; 80 had a primary diagnosis of ovarian cancer. ABT-767 demonstrated dose-proportional PK up to 500mg BID and half-life of 2h. Food had no effect on ABT-767 bioavailability. Most common grade 3/4 treatment-related adverse events were nausea, fatigue, decreased appetite, and anemia. Anemia showed dose-dependent increase. RP2D was 400mg BID. Objective response rate by RECIST 1.1 was 21% (17/80) in all evaluable patients and 20% (14/71) in evaluable patients with ovarian cancer. Response rate by RECIST 1.1 and/or CA-125 was 30% (24/80) in patients with ovarian cancer. Mutations in BRCA1 or BRCA2, homologous recombination deficiency (HRD), and platinum sensitivity were associated with tumor response. Median progression-free survival was longer for HRD positive (6.7months) versus HRD negative patients (1.8months) with ovarian cancer. Conclusions ABT-767 had an acceptable safety profile up to the established RP2D of 400mg BID and dose-proportional PK. Patients with BRCA1 or BRCA2 mutation, HRD positivity, and platinum sensitivity were more sensitive to ABT-767

A phase 1 study of PARP-inhibitor ABT-767 in advanced solid tumors with BRCA1/2 mutations and high-grade serous ovarian, fallopian tube, or primary peritoneal cancer

Purpose This phase 1 study examined safety, pharmacokinetics (PK), and efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-767 in patients with advanced solid tumors and BRCA1/2 mutations or with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Methods Patients received ABT-767 monotherapy orally until disease progression or unacceptable toxicity. Dose was escalated from 20 mg once daily to 500 mg twice daily (BID). Dose-limiting toxicities, recommended phase 2 dose (RP2D), food effect, objective response rate, and biomarkers predicting response were determined. Results Ninety-three patients were treated with ABT-767; 80 had a primary diagnosis of ovarian cancer. ABT-767 demonstrated dose-proportional PK up to 500 mg BID and half-life of ~2 h. Food had no effect on ABT-767 bioavailability. Most common grade 3/4 treatment-related adverse events were nausea, fatigue, decreased appetite, and anemia. Anemia showed dose-dependent increase. RP2D was 400 mg BID. Objective response rate by RECIST 1.1 was 21% (17/80) in all evaluable patients and 20% (14/71) in evaluable patients with ovarian cancer. Response rate by RECIST 1.1 and/or CA-125 was 30% (24/80) in patients with ovarian cancer. Mutations in BRCA1 or BRCA2, homologous recombination deficiency (HRD), and platinum sensitivity were associated with tumor response. Median progression-free survival was longer for HRD positive (6.7 months) versus HRD negative patients (1.8 months) with ovarian cancer. Conclusions ABT-767 had an acceptable safety profile up to the established RP2D of 400 mg BID and dose-proportional PK. Patients with BRCA1 or BRCA2 mutation, HRD positivity, and platinum sensitivity were more sensitive to ABT-767

Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo

Meeting Abstracts: Proceedings of the Thirteenth International Society of Sports Nutrition (ISSN) Conference and Expo Clearwater Beach, FL, USA. 9-11 June 201

Co-Culture of Amphibian Adrenal Cells: A Model of Medullary Control of Corticosteroidogenesis

115 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.Chromaffin-adrenocortical cellular interactions have become recognized as an important component of adrenocortical regulation, however, the mechanisms by which chromaffin cells modulate adrenocortical function are not well understood. To study chromaffin-adrenocortical cellular interactions directly, we developed primary frog (Rana pipiens) adrenal co-cultures. In these co-cultures, chromaffin cells extend processes that project toward or onto adrenocortical cells, mimicking their organization in vivo and indicating a potential for interaction between the two cell types. Furthermore, cultured chromaffin cells secrete norepinephrine, epinephrine and serotonin and respond to carbamylcholine, potassium, and veratridine stimulation; adrenocortical cells secrete a1dosterone and corticosterone and retain ACTH-responsiveness. To test whether chromaffin cells affect adrenocortical steroidogenesis, we used veratridine to selectively activate chromaffin cells. Prolonged chromaffin cell activation (24--96 hr) using 50 muM veratridine increased the number of contacts between chromaffin and adrenocortical cells and increased corticosterone secretion on days 3 (950%), and 4 (350%). alpha 2- and beta1,2-adrenergic and dopaminergic antagonists decrease corticosterone and aldosterone secretion while alpha2- and beta1,2-adrenergic agonists increase steroid secretion, suggesting that catecholamines mediate chromaffin-adrenocortical cellular interactions via these adrenergic receptor subtypes. Adrenocortical cell Fos protein expression was increased by chromaffin cell activation with 2 mM carbamylcholine (37%) or 50 muM veratridine (25%), demonstrating that chromaffin cell activation affects adrenocortical cells at the transcriptional level. The dynamic behavior of chromaffin and adrenocortical cells was assessed using time lapse microscopy. The effects of chromaffin cell activation on chromaffin cell morphology were evident within 30 minutes of verutridine treatment and included the establishment of growth cones, varicosities and rounded soma. Additionally, significant neurite outgrowth and branching, most often toward adrenocortical cells, was routinely observed, in contrast to control cultures. In both control and veratridine-treated cultures, substantial migration of adrenocortical cells towards chromaffin cells occurred, suggesting the presence of a trophic factor originating in the neuronal cells. Our results provide further evidence for reciprocal interactions between chromaffin and adrenocortical cells that affect cellular differentiation and modulation of steroid secretion. Furthermore, chromaffin and adrenocortical cells show activity-related plasticity that is likely to be important during development and in maintaining homeostasis.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Disparities in Use of Human Epidermal Growth Hormone Receptor 2–Targeted Therapy for Early-Stage Breast Cancer

PURPOSE: Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)–positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. METHODS: We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. RESULTS: Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). CONCLUSION: Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women