# High Intensity Interval Training: Optimizing Exercise Therapy to Mitigate Cardiovascular Disease Risk Following Breast Cancer Chemotherapy

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2023 · $228,750

## Abstract

PROJECT SUMMARY
Aging is a major risk factor for breast cancer and 80% of breast cancer cases are diagnosed after age 50.
Currently in the US, there are more than 3.8 million breast cancer survivors, and this number is expected to
increase dramatically due to the aging of the population. Chemotherapy is a highly effective treatment for breast
cancer but is associated with acute and long-term cardiovascular toxicity that may accelerate cardiovascular
aging, thus setting the stage for premature development of cardiovascular disease (CVD). Aerobic exercise is
recommended for CVD prevention, however, evidence on the optimal exercise prescription in breast cancer
survivors is limited. Breast cancer survivors often suffer from long-lasting cancer therapy-related side effects
(e.g., physical dysfunction, severe fatigue, muscle weakness, peripheral neuropathy, and balance impairments)
that may be compounded by age-related frailty and mobility issues (50% of breast cancer survivors are older
than age 60). These unique challenges may limit exercise feasibility, adherence, and in turn efficacy. High-
intensity interval training (HIIT) is attracting increasing attention as a time-efficient and potentially superior
aerobic exercise strategy for CVD prevention compared to moderate-intensity continuous training (MICT) in
clinical populations. We have recently adapted HIIT and MICT on an all-extremity non-weight-bearing exercise
(ANE) ergometer that eliminates balance concerns and distributes work between the upper and lower
extremities, compensating for weakness and fatigue. Our HIIT-ANE and MICT-ANE regimens are novel and
innovative exercise interventions for breast cancer survivors. Our central hypothesis is that HIIT-ANE will result
in greater and more durable improvements in endothelial and cardiac function compared with MICT-ANE and
usual care (UC) in breast cancer survivors who have recently completed chemotherapy. The aims of this
application are to conduct a randomized controlled trial to investigate: 1) the short-term and prolonged effects of
HIIT-ANE, MICT-ANE and UC on endothelial and cardiac function; and 2) the durability of the endothelial and
cardiac effects of HIIT-ANE vs. MICT-ANE. Women, 50 years of age and older, who have completed
chemotherapy within the past 6 months for primary, invasive, non-metastatic, stage I-III breast cancer will be
randomized to 1 of 3 groups: HIIT-ANE, MICT-ANE or UC. Exercise training will be performed 3 days/week over
12 weeks under supervision. The primary focus will be on endothelial and cardiac function assessed by flow-
mediated dilation and global longitudinal strain, respectively. Assessments will be performed at baseline, after
the 12-week exercise intervention and after a 12-week observation period. To gain mechanistic insight, we will
investigate circulating blood biomarkers and key biomarkers in endothelial cells harvested using a state-of-the-
art endovascular technique. This exploratory/developmental R...

## Key facts

- **NIH application ID:** 10667675
- **Project number:** 1R21AG078995-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Demetra Christou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $228,750
- **Award type:** 1
- **Project period:** 2023-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10667675

## Citation

> US National Institutes of Health, RePORTER application 10667675, High Intensity Interval Training: Optimizing Exercise Therapy to Mitigate Cardiovascular Disease Risk Following Breast Cancer Chemotherapy (1R21AG078995-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10667675. Licensed CC0.

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