Late cardiac effect of anthracycline therapy in physically active breast cancer survivors – a prospective study

Abstract

The late-onset cardiotoxic effect of anthracycline is known, however the early detection and prevention of subclinical myocardial damage has not been fully understood yet. Besides medical therapy regular physical activities may also play a role in the prevention and reduction of side effects of chemotherapy. The aim of our present study was to detect the effect of regular physical activities on the diastolic function and on the symptoms of late heart failure in case of anthracycline chemotherapy. The prospective study included 55 female patients (age 31-65 year, average 49.5 years) with breast cancer and no cardiovascular risk factors. Proper cardiologic checkup included physical examination (blood pressure, pulse, etc.), ECG, standard echocardiography parameters (EF, LV dimensions etc.) and specific tissue Doppler (TDI) measurements. Symptoms of heart failure were also recorded. After five years of follow-up, symptoms of heart failure were evaluated again. Patients were assigned into two groups depending on their physical activity: 36 patients did perform regular physical activities (mean age 49.2 years) and 19 patients did not (average age 50.1 years). There was no significant difference between the two groups in basic physiological or standard echocardiography parameters neither at the baseline nor at the later time points. Diastolic dysfunction (decreased E/A) was detected 6 months after the beginning of the treatment (T2 time point) in both groups. In the inactive group this value fell below one however there was no significant difference (1.1±0.25 vs. 0.95±0.22). One year after the beginning of the treatment (T3) a significant difference could be detected between the two groups (1.05±0.28 vs. 0.86±0.25. P=0.038). Consistent change in diastolic function (Ea/Aa) could be detected with the more sensitive TDI (Tissue Doppler Imaging) measurements after treatments in both groups, especially in the septal segment (in the non active group the Ea/Aa decreased markedly but not significantly at T2 - 1.1±0.55 vs. 0.81±0.44, and this difference became significant at T3 and 2 years after treatment (T4), p=0.007 and p=0.065). The filling pressure (E/Ea) rose above 10 (p=0.09) in the non active group at T2; and it kept rising in both groups and became significant at T3 (p=0.012). Five years after the onset of the treatment symptoms of heart failure were less frequently reported in the physically active group than in the inactive one (19.45% vs. 68.42%). The data of our study show that the diastolic dysfunction of the left ventricle related to the anthracycline therapy became evident in the physically active group later and the symptoms of heart failure were less frequent than in the non active group after five years period. Enrollment in sport activities could be a good means for partial prevention in this group of patients. Cardiologic checkup at proper intervals plays a pivotal role in detection of possible cardiotoxicity. This is a strong indication for changes in the lifestyle of the patient and the treatment protocol...

Strategies to Prevent Cardiovascular Toxicity in Breast Cancer: Is It Ready for Primetime?

“…Studies have shown fewer CV events in cancer patients who exercise on a regular basis. In a prospective analysis of 55 females with breast cancer who received anthracycline therapy, were 65 or younger, and had no CV risk factors, there were fewer symptoms of heart failure in physically active patients over a 5-year follow-up period [66]. There was also a delayed onset of diastolic dysfunction compared to inactive patients [66].…”

“…In a prospective analysis of 55 females with breast cancer who received anthracycline therapy, were 65 or younger, and had no CV risk factors, there were fewer symptoms of heart failure in physically active patients over a 5-year follow-up period [66]. There was also a delayed onset of diastolic dysfunction compared to inactive patients [66]. In another, larger prospective analysis of 2973 nonmetastatic breast cancer participants with an 8.6 year median follow-up, routine exercise of ≥9 MET-hour/week was associated with a reduction in CV events (new diagnosis of coronary artery disease, valve abnormality, arrhythmia, stroke, or CVD death) [67].…”

Physical activity during and after breast cancer therapy and associations of baseline physical activity with changes in cardiac function by echocardiography

“…8 There are limited prospective data on the associations between self-reported physical activity and changes in echocardiographic measures of systolic and diastolic function with breast cancer therapy. 9 In this cohort, we had previously defined both the changes in left ventricular systolic and diastolic function with exposure to cancer therapy, which are on the order of LVEF −6.6% (95% CI, −8.2, −5.0%), longitudinal strain 0.9% (95% CI, 0.3, 1.5%), E/e′ 0.8 (0.3, 1.4) for sequential doxorubicin and trastuzumab. 3,10 Here, we performed a detailed analysis of the changes in self-reported physical activity in a well-phenotyped cohort of 603 participants with breast cancer undergoing doxorubicin and/or trastuzumab therapy to determine: (a) changes in self-reported physical activity with cancer treatment; (b) baseline predictors of physical activity during and after cancer treatment; and (c) the associations between baseline self-reported physical activity and changes in echocardiography-derived parameters of systolic and diastolic function after cancer therapy.…”

Cardioprotective Effects of Exercise Training on Doxorubicin-Induced Cardiomyopathy: A Systematic Review With Meta-Analysis of Preclinical Studies

“…Exposure to exercise training before cancer diagnosis is associated with a 20-37% risk reduction of adverse cardiovascular events in patients with primary breast cancer [11]. However, while these evidences demonstrate that regular physical activity in cancer patients improve both oncological and cardiovascular outcomes [11][12][13][14], current literature still lacks of randomized clinical trials and stronger evidence in terms of modalities, duration, intensity and timing of exercise realization with regard to cancer treatment.…”