Stress and Depression Were Linked to Lasting Fatigue After Breast Cancer Treatment

Fatigue can remain a major concern for some people after breast cancer treatment. In this study, researchers examined whether long-term fatigue was more closely tied to changes in heart health, psychological symptoms, or features of cancer treatment.

The study included 381 participants: 236 people with stage I to III breast cancer and 145 people without cancer who served as comparison participants. The breast cancer group was receiving either potentially cardiotoxic chemotherapy, meaning chemotherapy that can affect the heart, or aromatase inhibitors. Aromatase inhibitors are medicines that lower estrogen levels and are used for some hormone-sensitive breast cancers.

Participants were enrolled at several community hospital-based cancer centers from May 2017 through July 2021. Their average age was 54 years, and they were followed for 24 months. Researchers measured fatigue before treatment and again over the study period using a standard questionnaire called the Functional Assessment of Chronic Illness Therapy Fatigue scale.

The team also collected information on depressive symptoms and perceived stress. Perceived stress describes how stressful people feel their lives are, rather than simply counting stressful events. They assessed heart function using measures including left ventricular ejection fraction, which estimates how much blood the heart’s main pumping chamber pushes out with each beat, and circumferential strain, a measure of how the heart muscle moves.

Two years after breast cancer treatment began, 33 people receiving potentially cardiotoxic chemotherapy, or 18.2%, had clinically relevant fatigue. The study also found that 62 people in this group, or 34.6%, had a meaningful increase in fatigue compared with their fatigue level before cancer treatment. Both results differed significantly from the aromatase inhibitor and noncancer comparison groups.

The researchers had expected chemotherapy-related changes in heart function to be connected with fatigue. But after accounting for factors such as heart measurements before and after treatment, age, body mass index, diabetes, high blood pressure, tobacco use, hematocrit, chemotherapy regimen, and certain heart-protective medicines, the clearest links with fatigue were depressive symptoms and perceived stress.

Changes in six-minute walk distance, a test of how far someone can walk in six minutes, were not associated with fatigue at 24 months. Neither were changes in ejection fraction or heart strain. The authors reported that depressive symptoms and perceived stress statistically mediated part of the relationship with later fatigue. In everyday terms, these psychological measures appeared to help explain the pattern of fatigue seen in the study data.

That does not mean stress or depression caused fatigue, or that heart health does not matter during cancer treatment. This was a cohort study, which follows people over time without assigning treatments at random. Fatigue itself could also affect mood and feelings of stress. The study cannot fully separate those possibilities or show whether improving stress or depressive symptoms would reduce fatigue.

The results apply most directly to the people studied: participants with stage I to III breast cancer receiving potentially cardiotoxic chemotherapy or aromatase inhibitors at community hospital-based cancer centers. They should not be assumed to apply to every breast cancer treatment setting or every person living with cancer-related fatigue.

The study points to an important next question: whether approaches that address depressive symptoms and perceived stress can prevent or lessen persistent fatigue. That would require future research designed to test specific approaches, rather than simply observe links between symptoms over time.