Less is more? Questioning the walking dose in the WISE trial

To the Editor,

We read with interest the WISE trial by Guth and colleagues, which examined whether a 24-week home-based walking program could prevent aromatase inhibitor (AI)-induced arthralgia in patients with early breast cancer [1]. The authors achieved excellent recruitment and adherence, and the intervention group walked significantly more steps than the control group. However, two points not discussed in the paper may help interpret the null finding.

First, the prescribed walking dose – 30 min of moderate-intensity walking on five days per week (150 min/week) – is substantially higher than the dose range recently associated with pain reduction in breast cancer survivors. A dose-response network meta-analysis by Huang and colleagues, which included 25 randomised controlled trials and 1899 patients, found that walking was significantly associated with pain relief within an effective dose range of 0–55 minutes per week, with the optimal effect observed at 55 min/week [2]. Beyond that range, no additional benefit was demonstrated – although the authors noted that the evidence for walking was based on only four study arms and was rated as very low quality [2]. The WISE trial prescribed 150 min/week of walking, nearly three times the upper bound of that range. While the optimal dose for AI-specific arthralgia may differ from general cancer-related pain, and while the evidence base for walking is still limited, the discrepancy is striking. It raises the possibility that the null result of the WISE trial may be partly attributable to a walking volume that lies outside the window in which benefit has been observed to date.

Second, the timing of pain assessment may have introduced bias. AI-associated arthralgia is characteristically worse after periods of inactivity (e.g., morning stiffness) and improves with movement [3]. The Brief Pain Inventory (BPI) “worst pain” item asks for the most severe pain in the preceding 24 hours. Patients who walked shortly before completing the questionnaire may have recalled pain that was temporarily relieved by the very intervention, thereby attenuating any difference between arms. This potential recall bias was not mentioned in the paper. A simple remedy would be to ask patients to rate pain at a standardised time before the first walk of the day.

In summary, the WISE trial provides valuable feasibility data, but its null result should not be interpreted as definitive evidence that walking cannot prevent AI-induced arthralgia. The possibility that a lower walking dose (e.g., 50–60 min/week) might be more effective than 150 min/week deserves investigation, as does the potential measurement bias from post-walking pain assessment. We hope these observations will inform the design of future physical activity trials in patients receiving AI therapy.

Ethics approval and consent to participate

Not applicable. This Correspondence does not report on or involve the use of any animal or human data or tissue.

Consent for publication

Not applicable. The manuscript does not contain any individual person's data in any form (including any individual details, images or videos).

Availability of data and materials

Not applicable. No datasets were generated or analysed during the current study.

Funding

This work was supported by China Health and Medical Development Foundation (chmdf2025-xrkt12-04 to Feng Yuan).

CRediT authorship contribution statement

Gai Liang: Conceptualization, Data curation, Formal analysis, Supervision, Validation, Writing – original draft. Feng Yuan: Conceptualization, Supervision, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.