Cardiovascular Late Effects and Exercise Treatment in Breast Cancer: Current Evidence and Future Directions

Abstract

Advances in detection and supportive care strategies have led to improvements in cancer-specific and overall survival after a diagnosis of early-stage breast cancer. These improvements, however, are associated with an increase in competing forms of morbidity and mortality, particularly cardiovascular disease (CVD). Indeed, in certain subpopulations of patients, CVD is the leading cause of mortality after early breast cancer, and these women also have an increased risk of CVD-specific morbidity, including an elevated incidence of coronary artery disease and heart failure compared with their sex- and age-matched counterparts. Exercise treatment is established as the cornerstone of primary and secondary prevention of CVD in multiple clinical populations. The potential benefits of exercise treatment to modulate CVD or CVD risk factors before, immediately after, or in the months/years after adjuvant therapy for early-stage breast cancer have received limited attention. We discuss the risk and extent of CVD in patients with breast cancer, review the pathogenesis of CVD, and highlight existing evidence from select clinical trials investigating the efficacy of structured exercise treatment across the CVD continuum in early breast cancer.

Figure 1

Exercise-CVD Continuum in Oncology. (1) primordial prevention – exercise initiated before or during primary adjuvant therapy (i.e., definitive surgery followed by radiotherapy, chemotherapy, or trastuzumab) to mitigate and/or attenuate potential therapy-induced toxicity, (2) primary prevention – exercise initiated following the cessation of primary adjuvant therapy to reverse / attenuate subclinical cardiovascular impairments, (3) secondary prevention – exercise initiated after the detection of a LVEF decline of ≥10% from baseline (pre-treatment) or beyond the lower limit of normal (<53%), poor VO_2peak (<15ml/kg/min), angina, transient ischemic attack, and (4) tertiary prevention – exercise initiated following detection of a new diagnosis of overt symptomatic HF, coronary artery disease, stroke, valve replacement, or serious arrhythmia following initiation of anticancer therapy.

Figure 2

Hypothetical phenogroups and precision exercise treatment that could be used to prevent/treat phenogroup-specific CVD sequelae. Cluster 1 patients have a prevalence of diabetes, dyslipidemia, decreased LV strain, eccentric remodeling, and elevated NT-proBNP. Cluster 2 patients have a prevalence of hypertension, vascular dysfunction, impaired LV relaxation, concentric LV remodeling, and low cardiovascular reserve. Each exercise treatment prescription would be individualized based on cardiovascular reserve testing (CPET) and/or strength testing, and the intensity and duration of training sessions would be sequenced in such a fashion that training volume is continually increased across the entire program. However, each patient cluster may have a unique exercise treatment focus. In cluster 1 patients, a sample precision exercise treatment prescription would incorporate more high intensity exercise training given the evidence that high intensity exercise has been shown to lower proBNP, reverse eccentric remodeling, and improve LV contraction. In cluster 2 patients, a sample precision exercise treatment prescription would incorporate more continuous and resistance exercise training given the evidence that moderate intensity continuous exercise and resistance exercise have been shown to improve vascular dysfunction, reverse concentric remodeling, and increase arterial-venous oxygen content difference (A-VO₂ Diff), thus improving cardiorespiratory fitness.