Fatigue Persists Two Years After Breast Cancer Treatment

Clinically relevant fatigue remained present in a subset of patients 2 years after they began breast cancer treatment and was associated more strongly with depressive symptoms and perceived stress than with measured cardiac function, according to a longitudinal prospective cohort study published in JAMA Network Open.

The study included 381 women, with a mean age of 54 years: 236 patients with stage I to III breast cancer who received potentially cardiotoxic chemotherapy or aromatase inhibitors and 145 comparators without cancer. Participants were followed for 24 months. Investigators measured fatigue before treatment and during follow-up, along with depressive symptoms, perceived stress, treatment factors, cardiovascular risk factors, 6-minute walk distance, and left ventricular function.

At 24 months, 18.2% of participants who received potentially cardiotoxic chemotherapy had clinically relevant fatigue, and 34.6% had a clinically significant increase from their pretreatment level (P < .001, relative to aromatase inhibitors and controls). Depressive symptoms were the principal mediator of the association between treatment group and 24-month fatigue, with perceived stress contributing secondarily. Changes in left ventricular ejection fraction and circumferential strain were not associated with 24-month fatigue.

Because the study was observational, the results establish associations rather than causation. Sixty-one participants withdrew before 24 months, although 84% supplied data at baseline, 3 months, and 24 months. The investigators used multiple imputation for missing data, and complete-case and imputed analyses were similar. The cohort was mostly White, and the noncancer comparator group was a convenience sample rather than a random sample.

The authors said the findings support considering screening for depressive symptoms and stress when fatigue remains present after treatment. They described the psychological mediation as partial and called for further study of possible immune, inflammatory, neuroendocrine, and neural contributors. The findings suggest that depressive symptoms and perceived stress contribute to posttreatment fatigue but do not establish that these factors fully explain it.

Source: Avis NE, O’Connell NS, Mihalko SL, et al. Long-term fatigue after treatment for breast cancer. JAMA Netw Open. 2026;9(8):e2629862. doi:10.1001/jamanetworkopen.2026.29862