Exercise habits prior to breast cancer diagnosis significantly affected the risk of recurrence in premenopausal women with certain tumor types in a large prospective cohort study.

The relationship was non-linear — i.e., past a certain point, more exercise was not associated with greater benefit, reported Ines Vaz-Luis, MD, PhD, of Gustave Roussy Institute in Villejuif, France, and colleagues in the Journal of Clinical Oncology.

They analyzed data on 10,359 patients enrolled in the multicenter Cancer Toxicities (CANTO) study and followed for 5.4 years. Exercise was assessed via questionnaire and quantified and standardized into “metabolic equivalent of task–hours per week” (MET-h/wk).

Patients who reported having at least 5 MET-h/wk pre-diagnosis — the equivalent of 1.5 hours a week of moderate exercise — had an 18% lower risk for distant recurrence (HR 0.82, 95% CI 0.61-1.00) compared with patients who exercised less. However, at a threshold above 25 MET-h/wk, the equivalent of 5 hours a week of moderate exercise, there was no additional risk reduction.

The benefit was found primarily in premenopausal patients with HR-negative/HER2-negative tumors (HR 0.59, 95% CI 0.38-0.92) and HR-negative/HER2-positive tumors (HR 0.37, 95% CI 0.14- 0.96), the investigators said.

“Our data suggest the hypothesis that exercise doses below and above a homeostatic zone (therapeutic range) confer suboptimal recurrence benefit, and potential antitumor effects of exercise may be confined to only certain subtypes in primary breast cancer,” the team concluded.

Vaz-Luis, who is director of the Cancer Survivorship Research Group, elaborated on the findings and the implications in the following interview.

Why did you decide to examine the effect of exercise on recurrence rather than survival?

Vaz-Luis: We know that higher levels of exercise, both before and after diagnosis, are associated with reduced all-cause and breast cancer-specific mortality. However, the impact on recurrence has been less studied. The impact of exercise on disease recurrence examined in this study provided an opportunity to rigorously evaluate the exercise-tumor progression link.

What mechanisms might be involved?

Vaz-Luis: Our data indicated that exercise doses exceeding a relatively modest amount (approximately 90 minutes of moderate exercise per week) were associated with greater risk reductions, but this benefit was observed only up to a certain limit (around 5 hours of moderate exercise per week). Beyond this threshold, no additional benefits were noted. This phenomenon may be linked to the adaptive response of cells and organisms to moderate stress.