Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum

To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO2peak]) across the breast cancer continuum and its prognostic significance in women with metastatic disease

Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

<p>Abstract</p> <p>Background</p> <p>MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer.</p> <p>Methods/Design</p> <p>One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer.</p> <p>Discussion</p> <p>Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in the prevention of trastuzumab-mediated cardiotoxicity. We expect the findings of this trial to provide important evidence in the development of guidelines for preventive therapy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01016886">NCT01016886</a></p

Age-Dependent Increased Odds of Cardiovascular Risk Factors in Cancer Survivors: Canadian Longitudinal Study on Aging Cohort

Background: This study compared the odds of self-reported and objectively measured cardiovascular (cv) risk factors in a sample of Canadian cancer survivors and individuals without cancer. Methods: A nationally representative sample of 45- to 85-year-old cancer survivors (n = 6288) in the Canadian Longitudinal Study on Aging were compared with individuals without cancer (n = 44,051). Results: The most prevalent risk factors in cancer survivors were all self-reported or easily measured in clinic: overweight or obesity (68.0%), former smoking (62.9%), fewer than 5 daily servings of fruits and vegetables (59.8%), hypertension (43.7%), and high waist circumference (47.0%). After adjustment for sex and education, the odds ratios of several cv risk factors varied by age in cancer survivors and the non-cancer controls. At ages 50 and 60, cancer survivors have increased odds of overweight or obesity, former smoking, hypertension, high waist circumference and truncal fat, diabetes, lung disease, and heart rate greater than 80 bpm compared with non-cancer controls. At age 70, odds did not differ for many risk factors; at age 80, no differences were evident. Without modification by age, low physical activity was more prevalent in cancer survivors (odds ratio: 1.27; 95% confidence interval: 1.17 to 1.39). There were no differences in the odds of cv risk factors measured by specialized equipment, including electrocardiography, carotid ultrasonography, spirometry, and dual-energy X-ray absorptiometry. Conclusions: The odds of several easy-to-assess cv disease risk factors are higher among middle-aged, but not older, cancer survivors relative to the general Canadian population. Initial assessment of cv risk for middle-aged adults in the survivorship setting could be quickly and inexpensively performed using self-reported and easily measured metrics