Tumor bearing in untreated breast cancer decreases exercise tolerance without lowering maximal oxygen uptake in rats

Breast cancer patients' maximal O₂ uptake (V̇O₂max) values average 60-80% of age-predicted values which is often attributed to adjuvant therapy rather than risk factors, comorbidities, or the tumor and associated factors (e.g., pro-inflammatory cytokines). It is crucial to understand the physiological mechanisms behind exercise intolerance in breast cancer patients to enhance targeted interventions; however, the effect of breast cancer, as an isolated condition on V̇O₂max, exercise tolerance, and resting cardiac function has not been investigated. We hypothesized that breast cancer, in the absence of underlying conditions or chemotherapy, would lower V̇O₂max, exercise tolerance, and cardiac function in proportion to tumor mass. Female Fischer-344 rats (~6-8 months, n = 8) were acclimatized to treadmill running for 5 days at 25 m/min for 5 min/day. To measure V̇O₂max, rats were placed within a plexiglass metabolic chamber connected to CO₂ and O₂ analyzers. Tests began at 25 m/min and increased (5 m/min) until exhaustion. Cardiac function was determined by echocardiography before rats received a mammary intraductal injection of rat adenocarcinoma cells (MATBIII, 6 × 10³ in 50 µl saline). Tumor growth was monitored daily and ~7 days following palpation (~24 days post-injection), V̇O₂max and echocardiography measurements were repeated. Tumor mass and volume were 2.1 ± 0.6 g and 1685 ± 428 (range 256-3749) mm³, respectively. Body mass (217 ± 6 vs 218 ± 6 g), V̇O₂max (72.1 ± 2.7 vs 70.0 ± 2.8 ml/kg·min; P > 0.05), and all measures of cardiac function were unchanged following tumor formation, with no significant correlation between tumor mass and V̇O₂max (P > 0.05). However, time to exhaustion (376 ± 20 vs 297 ± 25 s), final treadmill speed (48 ± 1 vs 42 ± 2 m/s), distance run (209 ± 16 vs 152 ± 18 m), and total work (45 ± 3 vs 32 ± 4 m·kg) were significantly reduced with tumor bearing. Contrary to our hypothesis, breast cancer did not affect V̇O₂max or cardiac function, but reduced exercise tolerance.