Effect of Eplerenone on Diastolic Function in Women Receiving Anthracycline-Based Chemotherapy for Breast Cancer.
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ABSTRACT:
SUBMITTER: Davis MK
PROVIDER: S-EPMC8352029 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Effect of Eplerenone on Diastolic Function in Women Receiving Anthracycline-Based Chemotherapy for Breast Cancer.
Davis Margot K MK Villa Diego D Tsang Teresa S M TSM Starovoytov Andrew A Gelmon Karen K Virani Sean A SA
JACC. CardioOncology 20191217 2
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Project description:Anthracycline chemotherapy is commonly used to treat breast cancer yet may increase the level of matrix metalloproteinases (MMP) -2 and -9, which increase the risk of atherosclerosis. While exercise has been shown to reduce the level of MMP in patients with diabetes, high intensity interval training (HIIT) has not been utilized to improve level of MMP in women with breast cancer receiving anthracycline chemotherapy. Thirty women were randomized to either 8-week HIIT or control (CON) group. The CON group was offered the HIIT intervention after 8 weeks. MMP-1, -2 -7, -9, tissue inhibitor of MMP (TIMP) -1, and-2 were measured at baseline and post-intervention. Repeated measures ANCOVA and paired t-test were performed to assess changes in MMP and TIMP. Post-intervention, no significant between-group differences were observed for MMP and TIMP. However, within-group decrease in MMP-9 was observed in the HIIT group [104.3(51.9) to 65.2(69.1); P = 0.01]. MMP-9 in the CON group was not significantly changed [115.5(47.2) to 90.4(67.9);]. MMP-2 significantly increased in both the HIIT group [76.6(11.2) to 83.2(13.1); P = 0.007) and the CON group [69.0(8.9) to 77.6(11.1) P = 0.003). It is unclear whether an 8-week HIIT intervention influences MMP-9 in breast cancer patients undergoing anthracycline chemotherapy. Additional investigations are required to understand the exercise-induced changes in MMP-2 and -9 in women undergoing anthracycline chemotherapy.
| S-EPMC7125197 | biostudies-literature
Project description:Anthracycline-based chemotherapy (ANT) remains among the most effective therapies for breast cancer. Cardiotoxicity from ANT represents a severe adverse event and may predominantly manifest as heart failure. While it is well-recognised that left ventricular systolic heart failure assessment is key in ANT-treated patients, less is known about the relevance of LV diastolic functional impairment and its characterisation. Studies reporting on echocardiographic diastolic function parameters before and after ANT in breast cancer patients without cardiac disease were included. We evaluated pulsed wave (E/A ratio and mitral E-wave deceleration time (EDT)) and tissue Doppler (mean velocities of the mitral ring in the early diastole (e') and E/e' ratio) echocardiographic parameters. A total of 892 patients from 13 studies were included. E/A ratio was significantly reduced at the end of ANT while EDT was not influenced by ANT. Additionally, e' and E/e' ratio showed no significant change after ANT. A modest reduction in LV ejection fraction and global longitudinal strain was observed at the end of ANT therapy. ANT had a modest early impact on E/A ratio, without changing EDT, e', or E/e' in patients with breast cancer without cardiac disease. Randomised studies on larger populations, using new parameters are required to define the role of diastolic dysfunction in the early diagnosis of ANT-induced cardiotoxicity.
| S-EPMC8432074 | biostudies-literature
Project description:Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC). From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R(2)=34%), complete tumour response (P=0.02, R(2)=12%), progressive disease (P<0.001, R(2)=38%) and time to progression (P<0.0001, R(2)=56%); R(2) is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good.
| S-EPMC2361525 | biostudies-other
Project description:Breast cancer is a heterogeneous group of diseases with diverse clinicopathological and molecular features. At present, chemo-resistance still poses a major obstacle to successful treatment of HER-2 negative breast cancer. Reliable biomarkers are urgently needed to accurately predict the therapeutic sensitivity and prognosis of such patients. In this study, we identified 3145 distant relapse-free survival (DRFS) associated genes in 310 patients with HER-2 negative breast cancer receiving taxane and anthracycline-based chemotherapy in the GSE25055 dataset using univariate survival analysis. Four genes (SRPK1, PCCA, PRLR and FBP1) were further selected by a robust likelihood-based survival model. A risk score model was then constructed with the regression coefficients of the four signature genes. Patients in the training set were successfully divided into high- and low-risk groups with significant differences in DRFS between the two groups. The predictive value was further validated in GSE25065 dataset and similar results were observed. Moreover, the 4-gene signature was proved to have superior prognostic power compared with several clinical signatures such as tumor size, lymph node invasion, TNM stage and PAM50 signature. Our findings indicated that the 4-gene signature was a robust prognostic marker with a good prospect of clinical application for HER-2 negative breast cancer patients receiving taxane-anthracycline combination therapy.
| S-EPMC5732731 | biostudies-literature
Project description:ImportanceSeveral studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue.ObjectiveTo determine whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with anthracycline-based chemotherapy.Design, setting, and participantsThe SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at 8 oncology departments in Italy. It was a prespecified interim analysis on the first 174 patients who had completed cardiac assessment at 12 months. The study recruitment was conducted between July 2015 and June 2020. The interim analysis was performed in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded.InterventionsCardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5 mg, once daily), ramipril (5 mg, once daily), and placebo, if tolerated.Main outcomes and measuresThe primary end point was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS).ResultsThe analysis was performed on 174 women (median age, 48 years; range, 24-75 years) who had completed a cardiological assessment at 12 months and reached the end of treatment. At 12 months, 3D-LVEF worsened by 4.4% in placebo arm and 3.0%, 1.9%, 1.3% in the ramipril, bisoprolol, ramipril plus bisoprolol arms, respectively (P = .01). Global longitudinal strain worsened by 6.0% in placebo arm and 1.5% and 0.6% in the ramipril and bisoprolol arms, respectively, whereas it was unchanged (0.1% improvement) in the ramipril plus bisoprolol arm (P < .001). The number of patients showing a reduction of 10% or greater in 3D-LVEF was 8 (19%) in the placebo arm, 5 (11.5%) in the ramipril arm, 5 (11.4%) in the bisoprolol, arm and 3 (6.8%) in the ramipril plus bisoprolol arm; 15 patients (35.7%) who received placebo showed a 10% or greater worsening of GLS compared with 7 (15.9; ramipril), 6 (13.6%; bisoprolol), and 6 (13.6%; ramipril plus bisoprolol) (P = .03).Conclusions and relevanceThe interim analysis of this randomized clinical trials suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodeling.Trial registrationClinicalTrials.gov identifier: NCT2236806.
| S-EPMC8391772 | biostudies-literature
Project description:PurposeWe examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines.MethodsWe used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS.ResultsOn Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS.ConclusionsWe observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.
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Project description:Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane-based chemotherapy.Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height2) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA).Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23-75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (<1,475 units) was significantly associated with hematologic (RR, 2.12; P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05).Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537-43. ©2017 AACR.
| S-EPMC5511549 | biostudies-literature
Project description:AimsPrognosis of patients for human epidermal growth factor receptor 2 (HER2)-negative breast cancer post neoadjuvant chemotherapy is not well understood. The aim of this study was to develop a novel pharmacophore-based signature to better classify and predict the risk of HER2-negative patients after anthracycline-and/or taxane-based neoadjuvant chemotherapy (NACT).Main methodsAnthracycline and taxane pharmacophore-based genes were obtained from PharmMapper. Drug-targeted genes (DTG) related clinical and bioinformatic analyses were undertaken in four GEO datasets.Key findingsWe used 12 genes from the pharmacophore to develop a DTG score (DTG-S). The DTG-S classification exhibited significant prognostic ability with respect to disease free survival (DFS) for HER2-negative patients who receive at least one type of neoadjuvant chemotherapy that included anthracycline and/or taxane. DTG-S associated with a high predictive ability for pathological complete response (pCR) as well as for prognosis of breast cancer. Using the DTG-S classification in other prediction models may improve the reclassification accuracy for DFS. Combining the DTG-S with other clinicopathological factors may further improve its predictive ability of patients' outcomes. Gene ontology and KEGG pathway analysis showed that the biological processes of DTG-S high group were associated with the cell cycle, cell migration, and cell signal transduction pathways. Targeted drug analysis shows that some CDK inhibitors and PI3K-AKT pathway inhibitors may be useful for high DTG-S patients.SignificanceThe DTG-S classification adds prognostic and predictive information to classical parameters for HER2-negative patients who receive anthracycline-and/or taxane-based NACT, which could improve the patients' risk stratification and may help guide adjuvant treatment.
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Project description:A chemotherapy induced phlebitis severity (CIPS) scale was developed in patients receiving anthracycline chemotherapy for breast cancer. A five-point severity scoring scale for chemotherapy-induced phlebitis was tested for inter-rater reliability. Ease of use was observed through timing assessments and a review of the completeness of documentation. A comparison of CIPS scale grade with participant reported severity scores was made. The final version was tested for inter-rater reliability, with 122 patient assessments. There was an 89.3% (109 of 122) agreement between the assessors (? = 0.82, SE ± 0.042, 95% CI 0.74-0.90). Mean time to complete the scale was 1 min 36 s and documentation was fully completed for 98% of assessments. Patient reported severity closely matched the CIPS grade (? = 0.54, SE ± 0.045, 95% CI 0.46-0.63). This new scale provides a list of symptoms associated with chemotherapy phlebitis, which can be scored quickly and accurately. It provides a reliable method for assessing chemotherapy-induced phlebitis, enabling a better understanding of its impact on patients' quality of life, and to inform the appropriate choice of peripheral or central intravenous administration. Multicentre testing of the CIPS scale is recommended.
| S-EPMC7141200 | biostudies-literature
Project description:Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.
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