The efficacy of Internet-based cognitive behavioral therapy for severely fatigued survivors of breast cancer compared with care as usual: A randomized controlled trial.

BACKGROUND: Severe fatigue is a common and distressing symptom affecting approximately one in four survivors of breast cancer. The current study examined the efficacy of Internet-based cognitive behavioral therapy (ICBT) for severe fatigue in survivors of breast cancer compared with care as usual (CAU). METHODS: The authors conducted a parallel-group randomized controlled trial. Severely fatigued, disease-free survivors of breast cancer who had completed cancer treatment at least 3 months previously were eligible. Participants were randomly allocated to ICBT or CAU using computer-generated stratified block randomization. The primary outcome of fatigue severity was assessed at baseline and after 6 months, as were the secondary outcomes of functional impairment, psychological distress, and quality of life. Statistical effects were tested with analyses of covariance (intention-to-treat analysis). RESULTS: Participants were recruited between January 2014 and March 2016 and assigned to ICBT (66 patients) or CAU (66 patients). Compared with the participants who had received CAU, those who had received ICBT reported lower fatigue scores at 6 months (mean difference [Δ], 11.5; 95% confidence interval [95% CI], 7.7-15.3) and a large effect size (Cohen d = 1.0), with the majority of patients (73%) demonstrating clinically significant improvement. ICBT also was found to lead to lower functional impairment (Δ, 297.8; 95% CI, 145.5-450.1) and psychological distress scores (Δ, 5.7; 95% CI, 3.4-7.9) and higher quality-of-life scores (Δ, 11.7; 95% CI, 5.8-17.7) compared with CAU, with medium to large effect sizes (Cohen d = 0.6-0.8). CONCLUSIONS: ICBT appears to be effective in reducing severe fatigue and related symptoms and meets the current need for easy accessible and more efficient evidence-based treatment options for severely fatigued survivors of breast cancer. Cancer 2017;123:3825-34. © 2017 American Cancer Society.

Angiotensin II-Receptor Inhibition With Candesartan to Prevent Trastuzumab-Related Cardiotoxic Effects in Patients With Early Breast Cancer: A Randomized Clinical Trial.

IMPORTANCE: This is the first randomized placebo-controlled evaluation of a medical intervention for the prevention of trastuzumab-related cardiotoxic effects. OBJECTIVE: To determine as the primary end point whether angiotensin II antagonist treatment with candesartan can prevent or ameliorate trastuzumab-related cardiotoxic effects, defined as a decline in left ventricular ejection fraction (LVEF) of more than 15% or a decrease below the absolute value 45%. DESIGN: This randomized, placebo-controlled clinical study was conducted between October 2007 and October 2011 in 19 hospitals in the Netherlands, enrolling 210 women with early breast cancer testing positive for human epidermal growth factor receptor 2 (HER2) who were being considered for adjuvant systemic treatment with anthracycline-containing chemotherapy followed by trastuzumab. INTERVENTIONS: A total of 78 weeks of candesartan (32 mg/d) or placebo treatment; study treatment started at the same day as the first trastuzumab administration and continued until 26 weeks after completion of trastuzumab treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was LVEF. Secondary end points included whether the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) can be used as surrogate markers and whether genetic variability in germline ERBB2 (formerly HER2 or HER2/neu) correlates with trastuzumab-related cardiotoxic effects. RESULTS: A total of 206 participants were evaluable (mean age, 49 years; age range, 25-69 years) 103 in the candesartan group (mean age, 50 years; age range, 25-69 years) and 103 in the placebo group (mean age, 50 years; age range, 30-67 years). Of these, 36 manifested at least 1 of the 2 primary cardiac end points. There were 3.8% more cardiac events in the candesartan group than in the placebo group (95% CI, -7% to 15%; P = .58): 20 events (19%) and 16 events (16%), respectively. The 2-year cumulative incidence of cardiac events was 0.28 (95% CI, 0.13-0.40) in the candesartan group and 0.16 (95% CI, 0.08-0.22) in the placebo group (P = .56). Candesartan did not affect changes in NT-proBNP and hs-TnT values, and these biomarkers were not associated with significant changes in LVEF. The Ala1170Pro homozygous ERBB2 genotype was associated with a lower likelihood of the occurrence of a cardiac event compared with Pro/Pro + Ala/Pro genotypes in multivariate analysis (odds ratio, 0.09; 95% CI, 0.02-0.45; P = .003). CONCLUSIONS AND RELEVANCE: The findings do not support the hypothesis that concomitant use of candesartan protects against a decrease in left ventricular ejection fraction during or shortly after trastuzumab treatment in early breast cancer. The ERBB2 germline Ala1170Pro single nucleotide polymorphism may be used to identify patients who are at increased risk of trastuzumab-related cardiotoxic effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00459771.