Project description:BackgroundMuscle dysfunction and sarcopenia have been associated with poor performance status, an increased mortality risk, and greater side effects in oncologic patients. However, little is known about how performance is affected by cancer therapy. We investigated muscle strength in breast cancer patients in different adjuvant treatment settings and also compared it with data from healthy individuals.MethodsBreast cancer patients (N = 255) from two randomized controlled exercise trials, staged 0-III and aged 54.4 ± 9.4 years, were categorized into four groups according to their treatment status. In a cross-sectional design, muscle function was assessed bilaterally by isokinetic dynamometry (0°, 60°, 180°/s) as maximal voluntary isometric contraction (MVIC) and maximal isokinetic peak torque (MIPT) in shoulder rotators and knee flexors and extensors. Additionally, muscular fatigue index (FI%) and shoulder flexibility were evaluated. Healthy women (N = 26), aged 53.3 ± 9.8 years, were tested using the same method. Analysis of covariance was used to estimate the impact of different cancer treatments on skeletal muscle function with adjustment for various clinical and socio-demographic factors.ResultsConsistently, lower muscle strength was measured in shoulder and knee strength in patients after chemotherapy. On average, patients had up to 25% lower strength in lower extremities and 12-16% in upper extremities in MVIC and MIPT during cancer treatment compared with healthy women. No substantial difference between patient groups in shoulder strength, but significantly lower shoulder flexibility in patients with radical mastectomy was measured. Chemotherapy-treated patients had consistently higher FI%. No serious adverse events were reported.ConclusionsBreast cancer patients showed markedly impaired muscle strength and joint dysfunctions before and after anticancer treatment. The significant differences between patients and healthy individuals underline the need of exercise therapy as early as possible in order to prevent or counteract the loss of muscle function after curative surgery as well as the consequences of neo-/adjuvant chemotherapy.
Project description:The purpose of this study is to find candidate biomarkers by analyzing proteins with differential amounts in 17 breast cancer patients’ plasmas with pathological complete response and 34 breast cancer patients’ plasmas without pathological complete response.
Project description:This nationwide population-based study investigated the differences in the risks of major adverse cardiovascular events (MACEs) among patients with hormone receptor-positive early-stage breast cancer undergoing different combinations of adjuvant treatments in Taiwan. Data from the National Health Insurance Research Database (NHIRD) and Taiwan Cancer Registry (TCR) along with the national mortality data were used. Patients who underwent surgery as the first mode of treatment were divided into four groups based on the subsequent adjuvant therapy received: hormone therapy (H), hormone therapy + chemotherapy (CH), hormone therapy + radiotherapy (RH), and hormone therapy + radiotherapy + chemotherapy (CRH) groups. The risks of fatal and nonfatal MACE among the groups were examined using the inverse probability of treatment weighted hazard ratio (IPTW-HR). Adjuvant treatment, age, tumour size, and comorbidities significantly affected the risks of MACEs among the 19,007 patients analysed. For nonfatal MACEs, the IPTW-HR was significantly lower in the CH group compare to the H group (0.704, 95% confidence interval [CI]: 0.516-0.961). No significant differences in the risks for fatal MACE were observed among the four groups. The IPTW-HRs for haemorrhagic stroke in the CH group was 0.424 (95% CI: 0.188-0.957), for congestive heart failure (CHF) in the RH group was 0.260 (95% CI: 0.088-0.762), and for ischaemic heart disease in the CRH group was 0.544 (95% CI: 0.317-0.934). Increase in the adjuvant modality does not necessarily increase the nonfatal or fatal MACE risks. Cardiac health should be monitored even in patients receiving hormone therapy alone.
Project description:BACKGROUND:The objective of this study was to assess factors that affect breast cancer patients' recall of patient assistance services. METHODS:We surveyed newly-diagnosed breast cancer patients and compared recall of receiving patient assistance services at 2 weeks and 6 months in a patient-assistance randomized controlled trial aimed to connect women to such programs. The intervention group received information about assistance programs targeted to their practical, psychosocial, and/or informational needs; the control group received a Department of Health pamphlet about breast cancer and its treatment, including a list of patient assistance services. FINDINGS:Of 333 women, 210 (63%) reported informational, 183 (55%) psychosocial and 177 (53%) practical needs. At 2 weeks, 96% (202/210) of women with informational needs reported receiving informational material but at 6 months, recall dropped to 69% (140/210). All women whose informational needs were met recalled receiving information, compared to 31% whose needs were unmet (p?<?0.0001). Of 109 intervention patients with psychosocial or practical needs, 77% (79) contacted a program specified in their action plan at 2 weeks. However, at 6 months, only 39% (31/79) recalled contacting a program. Women without recall were less likely to report having their needs met (6% vs. 58%; p?<?0.001). CONCLUSIONS:Recall of patient assistance services is strongly related to having needs met. Use of patient surveys to evaluate utilization or impact of such programs should be used with caution due to poor patient recall. CLINICAL TRIALS # NCT00233077: http://www.clinicaltrials.gov/ct2/show/NCT00233077?term=Nina+Bickell&rank=2.
Project description:Detecting SNPs associated with drug efficacy or toxicity is helpful to facilitate personalized medicine. Previous studies usually find SNPs associated with clinical outcome only in patients received a specific treatment. However, without information from patients without drug treatment, it is possible that the detected SNPs are associated with patients' clinical outcome even without drug treatment. Here we aimed to detect drug response SNPs based on data from patients with and without drug treatment through combing the cox proportional-hazards model and pairwise Kaplan-Meier survival analysis. A pipeline named Detection of Drug Response SNPs (DDRS) was built and applied to TCGA breast cancer data including 363 patients with doxorubicin treatment and 321 patients without any drug treatment. We identified 548 doxorubicin associated SNPs. Drug response score derived from these SNPs were associated with drug-resistant level (indicated by IC50) of breast cancer cell lines. Enrichment analyses showed that these SNPs were enriched in active epigenetic regulation markers (e.g., H3K27ac). Compared with random genes, the cis-eQTL genes of these SNPs had a shorter protein-protein interaction distance to doxorubicin associated genes. In addition, linear discriminant analysis showed that the eQTL gene expression levels could be used to predict clinical outcome for patients with doxorubicin treatment (AUC = 0.738). Specifically, we identified rs2817101 as a drug response SNP for doxorubicin treatment. Higher expression level of its cis-eQTL gene GSTA1 is associated with poorer survival. This approach can also be applied to identify new drug associated SNPs in other cancers.
Project description:BackgroundThe expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints.MethodsWe examined serial samples from 40 older women with triple-negative or hormone receptor-positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks).ResultsCH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P = .02).ConclusionsOur study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies.Trial registrationClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322.
Project description:Although gemcitabine monotherapy is the standard treatment for advanced pancreatic cancer, patient outcome varies significantly, and a considerable number do not benefit adequately. We therefore searched for new biomarkers predictive of overall patient survival. Using LC-MS, we compared the base-line plasma proteome between 29 representative patients with advanced pancreatic cancer who died within 100 days and 31 patients who survived for more than 400 days after receiving at least two cycles of the same gemcitabine monotherapy. Identified biomarker candidates were then challenged in a larger cohort of 304 patients treated with the same protocol using reverse-phase protein microarray. Among a total of 45,277 peptide peaks, we identified 637 peaks whose intensities differed significantly between the two groups (p < 0.001, Welch's t test). Two MS peaks with the highest statistical significance (p = 2.6 x 10(-4) and p = 5.0 x 10(-4)) were revealed to be derived from alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, respectively. The levels of alpha(1)-antitrypsin (p = 8.9 x 10(-8)) and alpha(1)-antichymotrypsin (p = 0.001) were significantly correlated with the overall survival of the 304 patients. We selected alpha(1)-antitrypsin (p = 0.0001), leukocyte count (p = 0.066), alkaline phosphatase (p = 8.3 x 10(-8)), and performance status (p = 0.003) using multivariate Cox regression analysis and constructed a scoring system (nomogram) that was able to identify a group of high risk patients having a short median survival time of 150 days (95% confidence interval, 123-187 days; p = 2.0 x 10(-15), log rank test). The accuracy of this model for prognostication was internally validated and showed good calibration and discrimination with a bootstrap-corrected concordance index of 0.672. In conclusion, an increased level of alpha(1)-antitrypsin is a biomarker that predicts short overall survival of patients with advanced pancreatic cancer receiving gemcitabine monotherapy. Although an external validation study will be necessary, the current model may be useful for identifying patients unsuitable for the standardized therapy.
Project description:AimThe aim of the study was to assess the safety of surgery for breast cancer in patients with antithrombotic therapy (ATT), including antiplatelet therapy (APT) and anticoagulation therapy (ACT) for thromboembolic risks.MethodsOne hundred ninety-three consecutive patients receiving breast surgery for breast cancer at our institution between 2010 and 2015 were retrospectively reviewed. Among them, ATT was regularly used in 50 patients (25.9%). Our perioperative management included maintenance of preoperative aspirin monotherapy for APT and bridging heparin for ACT in patients at high thromboembolic risks and early postoperative reinstitution in all ATT cases. The outcome variables of patients with ATT (ATT group) were compared to those of patients without ATT (non-ATT group), and the significant risk factors for postoperative complications were determined by multivariate analysis.ResultsThis series included 127 mastectomy and 66 breast-conserving surgery. ATT group showed significantly high frequency of history of cerebral infarction and percutaneous coronary intervention (PCI). In the ATT group, 32 patients (16.6%) were categorized as high risk for thromboembolism, but there was neither thromboembolic event nor perioperative death in the whole cohort. Surgical blood loss and rates of intraoperative transfusion were identical between the groups. Whereas overall postoperative bleeding complication was more frequently observed in the ATT group compared to the non-ATT group (12.0% vs. 3.5%, p=0.360) in univariate analyses, multivariate analysis showed that neither ATT nor preoperative aspirin continuation affected postoperative bleeding complications.ConclusionEven in patients undergoing ATT, surgery for breast cancer is safely performed without any increase in blood loss or postoperative bleeding, and no thromboembolism was experienced in the series. Our perioperative management of ATT patients is valid during breast surgery, although this patient population is still challenging and should be rigorously managed.