New research finds depression and stress — not just heart function — drive long-term fatigue for breast cancer survivors
Recent findings from a multisite study, involving VCU Health Pauley Heart Center and Wake Forest University School of Medicine, could change how breast cancer care teams approach mental health and heart screenings.
August 20, 2026
New research suggests that that psychological factors are more connected to fatigue experienced by breast cancer survivors than changes in heart function. (Getty Images)
By Tanner Lambson
More than a third of women receiving chemotherapy for breast cancer experience significant fatigue two years after starting their treatment, a side effect that can reduce their quality of life.
Researchers have long suspected this fatigue is linked to the cardiotoxic effects of chemotherapy that can damage the heart. However, new research involving VCU Health Pauley Heart Center and Wake Forest University School of Medicine suggests that psychological factors like depressive symptoms and stress provide a greater link to fatigue experienced by breast cancer survivors than changes in heart function.
"This research is remarkable because it challenges our assumptions about what actually drives fatigue in breast cancer survivors," said W. Gregory Hundley, M.D., the study’s principal investigator and senior author and director of Pauley Heart Center and a member of the Cancer Prevention and Control research program at VCU Massey Comprehensive Cancer Center. "As a cardiologist, my instinct is always to look first at the heart. Wh0at this study tells us is that, in this case, the answer can lie elsewhere."
The study, recently published in JAMA Network Open, stems from a collaboration among researchers from VCU Health Pauley Heart Center, VCU Massey Comprehensive Cancer Center, Wake Forest University School of Medicine, Perelman School of Medicine at the University of Pennsylvania, Novant Health Heart & Vascular Institute, Harold C. Simmons Comprehensive Cancer Center and University of Washington School of Nursing.
“This research is important because it highlights the role of factors other than cardiovascular function in contributing to fatigue in breast cancer patients receiving chemotherapy and suggests avenues for reducing fatigue,” said Nancy Avis, Ph.D., professor in the Department of Social Sciences and Health Policy at the Wake Forest University School of Medicine, member of the Atrium Health Wake Forest Baptist Comprehensive Cancer Center and the study’s lead author.
How stress and depressive symptoms contribute to long-term fatigue after breast cancer treatment
This paper is the result of research conducted through the Understanding and Predicting Breast Cancer Events after Treatment (UPBEAT) study; Hundley is the project’s lead researcher.
UPBEAT followed 381 participants — 236 women with stage I to III breast cancer and 145 without a cancer diagnosis — across 66 community hospitals between 2017 and 2021. Participants were tracked for 24 months; those with a breast cancer diagnosis received chemotherapy or hormone therapy during that time, while the women without a cancer diagnosis were monitored to for any changes in fatigue.
Fatigue was measured using the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale. Participants were found to have “notable fatigue” if they had a score of 30 or lower on the FACIT scale, or a drop of five or more points from their first evaluation. Study participants were also examined for changes in heart function that could contribute to fatigue symptoms, including how far they could walk in six minutes, how much blood their heart could pump in one beat and how hard their heart worked to pump blood.
Key findings of the study included:
- 18% of women receiving chemotherapy experienced “notable fatigue” compared to women on hormone therapy or in the control group.
- 35% of women undergoing chemotherapy had a large increase in fatigue compared to their fatigue levels before breast cancer treatment began.
- After accounting for cardiovascular risk factors — which include diabetes, high blood pressure, tobacco use, age, body mass index (BMI) and the type of chemotherapy received — depressive symptoms and stress were more likely to contribute to fatigue after two years.
- Cardiovascular changes experienced by participants were not associated with fatigue.
“Nearly one in five women treated with potentially cardiotoxic chemotherapy reported fatigue two years after treatment began, and more than a third experienced a meaningful worsening of fatigue compared with their pre-treatment baseline. The fact that these outcomes were more closely associated with stress and depression than with objective cardiovascular measures shows the complexity of cancer-related fatigue,” said Pamela Jill Grizzard, MS, study co-author and assistant director of research compliance and regulatory affairs at Pauley Heart Center.
Mental health screenings for breast cancer survivors might be just as important as treating heart health
Chemotherapy and hormone therapies used to treat breast cancer are well-known to affect nearly every part of the body. While cardiac monitoring is a major focus of cardio-oncologists because of the risks of treatment-related cardiotoxicity, this study suggests that cardiologists and cardio-oncologists seeking to understand and manage cancer-related fatigue should also investigate factors beyond heart function.
The researchers note that these findings could reshape how cancer survivorship care teams approach long-term fatigue, shifting more attention toward mental health screening and support, alongside cardiac monitoring.
More research is needed to determine whether targeted interventions for depression and stress can meaningfully reduce fatigue in breast cancer survivors, and whether similar patterns hold across other cancer types and treatment regimens.
"As cancer therapies continue to improve, more patients are surviving and living longer with the lasting effects of their treatment, including fatigue,” Hundley said. “Cardiologists and cardio-oncologists are seeing more of these survivors in their clinics, which makes it essential that we understand what's actually driving fatigue that often diminishes quality of life. In addition to treating cancer and protecting the heart during cancer treatment, it's important to understand the causes of post-cancer-treatment fatigue and develop programmatic solutions to prevent this fatigue that can be quite debilitating.”
Other Virginia Commonwealth University researchers include Jennifer Jordan, Ph.D., associate professor in VCU College of Engineering and member of the Cancer Prevention and Control research program at VCU Massey Comprehensive Cancer Center; Amy Ladd, Ph.D., associate director of Pauley Heart Center; Kristine Olson, Ph.D., science writer with Pauley Heart Center; Moriah Bellissimo, Ph.D., postdoctoral researcher with Pauley Heart Center; Mary Helen Hackney, M.D., MS, FACP, Commonwealth Endowed Professorship in Breast Cancer Excellence at VCU School of Medicine and medical director of community oncology at VCU Massey Comprehensive Cancer Center; Alexander Lucas, Ph.D., postdoctoral researcher with Pauley Heart Center and member of the Cancer Prevention and Control research program at VCU Massey Comprehensive Cancer Center; and F. Gerard Moeller, M.D., director of the VCU C. Kenneth and Dianne Wright Center for Clinical and Translational Research.
The UPBEAT study (Understanding and Predicting Breast Cancer Events after Treatment) was sponsored by Wake Forest University Health Sciences (WF-97415) and the National Cancer Institute (R01CA199167) and conducted through the Wake Forest NCI Community Oncology Research Program Research Base and the ECOG-ACRIN Cancer Research Group. The study is registered with ClinicalTrials.gov (NCT02791581).
