Mechanisms and Efficacy of Physical Activity to Reduce Cardiovascular Morbidity in Women with Breast Cancer

PROJECT SUMMARY
Reduced exercise capacity is the hallmark symptom of heart failure (HF) and the primary morbidity experienced
by women treated for breast cancer (BC). No established therapies exist to mitigate treatment-related declines
in exercise capacity and lower HF risk in BC survivors. We found that meeting physical activity (PA)
recommendations during the first 3 months of BC treatment was associated with preserved exercise capacity.
Yet, nearly 80% of women were inactive during treatment. While center-based aerobic PA and/or strength
training programs maintain exercise capacity during and after BC treatment, they are structured programs and
typically have low adherence due to time constraints, travel barriers, persistent fatigue, and compromised
immunity during BC treatment. Generalizability of these trials is limited as only the most motivated and physically
active individuals enroll. Thus, there is a need for feasible and practical PA programs to engage women with BC.
Recent work highlights the value of lifestyle PA to reduce HF risk by improving exercise capacity. Interventions
that target lifestyle PA, such as vigorous intermittent lifestyle physical activity (VILPA), can heighten access for
women with BC and attract time-limited and less physically active participants. VILPA is characterized by brief
bouts of vigorous PA completed during activities of daily living and is associated with a 48% reduction in
cardiovascular (CV) mortality compared to inactivity. Small amounts of VILPA (3 minutes/week) have shown
improvements in exercise capacity in non-cancer populations. However, the efficacy of a VILPA solution for
preserving exercise capacity in BC patients is unknown. Additionally, the mechanisms underlying PA benefits
are unknown, which creates a major gap for refining PA-based interventions and maximizing efficacy. In this K99
project, prior to testing VILPA in a clinical trial (R00), I will examine mechanisms underlying the association of
PA to preserve exercise capacity. I will test if increased PA participation in the first 3 months of BC treatment is
associated with preserved muscle quality and/or mitigated inflammation (both contributors to exercise
intolerance). In the R00, following the ORBIT model of behavioral interventions, I will conduct a Phase IIb
randomized trial testing the preliminary efficacy of VILPA versus a healthy living comparator to preserve exercise
capacity during BC treatment while prospectively assessing inflammation and muscle quality. Through this
award, I will learn 1) CV and exercise capacity outcome assessments, 2) systemic inflammation related to cardiac
injury, 3) design and implementation of behavioral clinical trials, and 4) analytical approaches for behavioral
clinical trials. With guidance from outstanding mentors, I will gain skills to launch an independent career and
deliver lifestyle interventions targeting mechanisms that contribute to reduced exercise capacity. Findings from
this proposal could change clinical care of cancer patients by providing a feasible and accessible PA solution to
improve CV outcomes for women with BC and potentially other cancer types.

Grant Number: 1K99HL173554-01A1
NIH Institute/Center: NIH
Principal Investigator: Moriah Bellissimo