Cardiorespiratory fitness and male breast cancer association: The ETHOS Cohort.
BACKGROUND Male breast cancer is a rare but increasingly recognized disease with limited data on modifiable risk factors. Specifically, it is not known if the inverse association between cardiorespiratory fitness (CRF) and breast cancer risk reported in women is similar to the association between CRF and breast cancer in men. The study aimed to evaluate the association between CRF and the incidence of male breast cancer in a large, nationally representative cohort of U.S. Veterans. METHODS We analyzed data from 777,618 male Veterans who completed an exercise treadmill testing (ETT) between 1999 and 2024 within the Veterans Health Administration and had no evidence of breast cancer prior to the ETT. CRF was expressed in peak metabolic equivalents (METs). The cohort was categorized into 4 age-adjusted CRF categories based on the peak METs achieved. The primary outcome was incident male breast cancer, ascertained through the Veterans Affairs Computerized Patient Record System. Cox proportional hazards models were used to estimate hazard ratios (HRs) for breast cancer incidence across CRF categories, adjusted for age, race, body mass index, hypertension, diabetes (T2DM), chronic kidney disease, smoking, and alcohol use. RESULTS Over a median follow-up of 10.7 years 518 men were diagnosed with breast cancer. After multivariable adjustment, age (HR = 1.24, 95% confidence interval (95%CI): 1.14-1.36) per decade, chronic kidney disease (HR = 2.13; 95%CI:1.41-3.23), hypertension (HR = 1.57; 95%CI: 1.28-1.92), T2DM (HR = 1.24; 95%CI: 1.02-1.51), and poor CRF (HR = 1.69; 95%CI: 1.24-2.30) were the strongest predictors of breast cancer. Compared to patients in the lowest CRF category, breast cancer risk was 41% lower for individuals in the highest CRF quartile (HR = 0.59; 95%CI: 0.44-0.81). CONCLUSION Higher CRF was independently associated with a substantially lower risk of breast cancer in men. These findings suggest that CRF may represent a modifiable risk factor in the prevention of male breast cancer, underscoring the broader importance of physical fitness in reducing cancer risk across sexes.