Fig 1.

Trajectory decline in cardiovascular reserve capacity (CVRC) across the breast cancer survivorship continuum. The postulated trajectories of decline in CVRC in patients with early-stage breast cancer (gold lines) compared with age-matched decline in women without a history of breast cancer (blue line). Specifically, (A) at diagnosis, baseline CVRC is determined by nonmodifiable (age, genetic predisposition) and modifiable risk factors (eg, hypertension, obesity, physical inactivity). (B) After initiation of adjuvant therapy, the extent and magnitude of decline in CVRC is determined by the direct and indirect effects of the selected treatment management plan and its interaction with modifiable and nonmodifiable risk factors. Several trajectories of change in CVRC, as assessed by left ventricular ejection fraction and cardiorespiratory fitness, have been observed (C) after completion of adjuvant therapy: continued declines in CVRC,^28,49 spontaneous acute recovery,⁵⁰ and plateau.⁵¹ Ultimately, however, similar to age-matched women without a history of cancer, patients with breast cancer are subjected to normal age-related and comorbid pathologies. As CVRC depletes below a critical threshold, asymptomatic maladaptation occurs, which, without intervention, leads to overt clinical dysfunction (eg, heart failure, myocardial infarction) and ultimately chronic morbidity and premature mortality.