scholarly journals Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-5103

2017 ◽  
pp. 1-9 ◽  
Author(s):  
Bryan P. Schneider ◽  
Fei Shen ◽  
Guanglong Jiang ◽  
Anne O’Neill ◽  
Milan Radovich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
The United States ◽  
Genetic Ancestry ◽  
Phase Iii ◽  
European Ancestry ◽  
Induced Hypertension ◽  
The Impact ◽  
Dose Reductions

Purpose Racial disparity in breast cancer outcomes exists between African American and white women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOG-ACRIN-5103. The primary efficacy end point, invasive disease–free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results Overall, AAs had significantly inferior DFS ( P = .002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor–positive subgroup ( P = .03), with a similar, nonsignificant trend for those who had triple-negative breast cancer ( P = .12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10−11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P = .02), with a trend for more congestive heart failure (OR, 1.8; P = .08). AAs had significantly more dose reductions in paclitaxel ( P = 6.6 × 10−6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS ( P = .03), whereas in EAs, dose reductions did not have an impact on outcome ( P = .35). Conclusion AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN-5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population.

Impact of African ancestry on the relationship between BMI and survival in early stage breast cancer: Retrospective analysis from E5103.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1010-1010
Author(s):  
Tarah Jean Ballinger ◽  
Guanglong Jiang ◽  
Fei Shen ◽  
Kathy Miller ◽  
Bryan P. Schneider
Keyword(s):  
Breast Cancer ◽  
Racial Disparities ◽  
Early Stage ◽  
African Ancestry ◽  
Genetic Ancestry ◽  
Early Stage Breast Cancer ◽  
European Ancestry ◽  
A Genome ◽  
The Impact ◽  
The Relationship

1010 Background: Both Black race and obesity are associated with worse survival in early stage breast cancer. Obesity disproportionately affects Black women; however, the degree this contributes to racial disparities in breast cancer remains unclear. Prior work evaluated heterogeneous populations or used self- reported race, rather than genetic ancestry. African ancestry is associated with higher BMI and worse survival in breast cancer; however, the intersection between genetic ancestry and obesity on survival outcomes remains unknown. Methods: We analyzed data from the adjuvant trial E5103. Patients with high risk, HER2 negative breast cancer received doxorubicin/cyclophosphamide x 4, followed by weekly paclitaxel x 12, with or without bevacizumab. Genetic ancestry was determined on the 2,854 patients with available germline DNA, BMI, and outcome data using principal components from a genome-wide array. The primary objective assessed impact of BMI on DFS and OS by ancestry. Multivariate Cox proportional hazard models evaluated correlation between continuous or binary BMI and survival in African (AA) and European (EA) Americans. Results: 13.4% of patients were genetically classified as AA and 86.6% as EA. Higher continuous BMI was significantly associated with worse DFS and OS only in AAs (DFS: HR = 1.25 95% CI 1.07-1.46, p = 0.004; OS: HR = 1.38 95% CI 1.10-1.73, p = 0.005); not in EAs (DFS HR = 0.97 95% CI 0.90-1.05, p = 0.50; OS HR = 1.03 95% CI 0.93-1.14, p = 0.52). By disease subtype, BMI was associated with worse outcomes only in AAs with ER+, and not TNBC. By categorical BMI, WHO class III obesity (³ 40) significantly associated with worse DFS and OS only in AAs (DFS HR = 1.98, p = 0.010; OS HR = 2.07, p = 0.064), not in EAs (DFS HR = 0.97, p = 0.86; OS HR = 1.28, p = 0.30). Proportion of African ancestry (proAA) was associated with higher BMI and worse outcomes in the total population; however, within AAs there was no significant interaction between proAA and BMI on DFS (HR = 0.36, p = 0.06) or OS (HR = 0.38, p = 0.24). In AAs, BMI remained associated with DFS (HR = 2.78, p = 0.019), suggesting higher BMI is associated with worse DFS regardless of proAA. Coefficients for the interaction term indicate that as proAA increases the impact of BMI on outcome is lessened. Conclusions: Higher BMI is significantly associated with worse breast cancer outcomes in women of African ancestry in E5103, but not in those of European ancestry. Categorically, this association was significant only for severe obesity, indicating the relationship may depend on the degree of obesity. As proAA increased in AAs, the impact of BMI on outcome was lessened, suggesting other host factors may contribute more to obesity’s influence on outcome than genetics. Determination of the optimal populations for weight loss interventions will advance precision medicine efforts to impact racial disparities and outcomes in early stage breast cancer.

Small animal Review

2021 ◽  
Vol 26 (3) ◽  
pp. 5-5
Author(s):  
Alex Gough
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Pulmonary Oedema ◽  
Potential Role ◽  
Lung Ultrasound ◽  
Small Animal ◽  
Shock Index ◽  
Cardiogenic Pulmonary Oedema ◽  
The Impact

Summary In this month's Small Animal Review, we summarise three recently published papers from other veterinary journals. The papers for this issue explore the impact of open registries on inbreeding, in the working Australian Kelpie population particularly, and the impact of vehicle trauma on the canine shock index, as well as the potential role for lung ultrasound in monitoring for cardiogenic pulmonary oedema in dogs being treated for left-sided congestive heart failure.

scholarly journals Standards of laboratory practice: cardiac drug monitoring

1998 ◽  
Vol 44 (5) ◽  
pp. 1096-1109 ◽  
Author(s):  
Roland Valdes ◽  
Saeed A Jortani ◽  
Mihai Gheorghiade
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Drug Monitoring ◽  
Free Fraction ◽  
Therapeutic Index ◽  
Therapeutic Monitoring ◽  
Therapeutic Drug ◽  
Laboratory Practice ◽  
Clinical Complications ◽  
The Impact

Abstract In this Standard of Laboratory Practice we recommend guidelines for therapeutic monitoring of cardiac drugs. Cardiac drugs are primarily used for treatment of angina, arrhythmias, and congestive heart failure. Digoxin, used in congestive heart failure, is widely prescribed and therapeutically monitored. Monitoring and use of antiarrhythmics such as disopyramide and lidocaine have been steadily declining. Immunoassay techniques are currently the most popular methods for measuring cardiac drugs. Several reasons make measurement of cardiac drugs in serum important: their narrow therapeutic index, similarity in clinical complications and presentation of under- and overmedicated patients, need for dosage adjustments, and confirmation of patient compliance. Monitoring may also be necessary in other circumstances, such as assessment of acetylator phenotypes. We present recommendations for measuring digoxin, quinidine, procainamide (and N-acetylprocainamide), lidocaine, and flecainide. We discuss guidelines for measuring unbound digoxin in the presence of an antidote (Fab fragments), for characterizing the impact of digoxin-like immunoreactive factor (DLIF) and other cross-reactants on immunoassays, and for monitoring the unbound (free fraction) of drugs that bind to α1-acid glycoprotein. We also discuss logistic, clinical, hospital, and laboratory practice guidelines needed for implementation of a successful therapeutic drug monitoring service for cardiac drugs.

scholarly journals Congestive heart failure-related hospital deaths across the urban-rural continuum in the United States

2019 ◽  
Vol 16 ◽  
pp. 101007
Author(s):  
Kristin Primm ◽  
Alva O. Ferdinand ◽  
Timothy Callaghan ◽  
Marvellous A. Akinlotan ◽  
Samuel D. Towne ◽  
...  
Keyword(s):  
United States ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
The United States ◽  
Urban Rural ◽  
Hospital Deaths

Atrial fibrillation and congestive heart failure: what is the impact of long-term anticoagulation on outcomes

2004 ◽  
Vol 10 (4) ◽  
pp. S110
Author(s):  
Lynn G. Tarkington ◽  
Salvatore L. Battaglia ◽  
April W. Simon ◽  
Steven D. Culler ◽  
Edmund R. Becker ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Congestive Heart Failure ◽  
The Impact

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

Kwashiorkor in the United States

PEDIATRICS ◽  
1980 ◽  
Vol 66 (6) ◽  
pp. 972-976
Author(s):  
H. Peter Chase ◽  
Vijay Kumar ◽  
Richard T. Caldwell ◽  
Donough O'Brien
Keyword(s):  
United States ◽  
Heart Failure ◽  
Congestive Heart Failure ◽  
Skin Rash ◽  
The United States ◽  
Protein Restriction ◽  
Bleeding Tendency ◽  
Parenteral Alimentation

Kwashiorkor, with typical edema and skin rash is occasionally seen in affluent countries as a result of severe protein restriction. Treatment is with a lactose-free formula after rehydration and sometimes after a period of parenteral alimentation. Complications of therapy included: diarrhea, congestive heart failure, infections, a bleeding tendency, and seizures. Two of the 14 children in this series died.

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