Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features in Early Stage Breast Cancer: The LACE and Pathways Studies

摘要

To investigate whether the impact of post-diagnosis exercise on breast cancer outcomes in women diagnosed with early stage breast cancer differs on the basis of tumor clinicopathologic and molecular features. Using a prospective design, 6,211 patients with early stage breast cancer from two large population-based cohort studies were studied. Age-adjusted and multivariable Cox regression models were performed to determine the relationship between exercise exposure (total MET-hrs·wk⁻¹) and recurrence and breast cancer death for: (1) all patients (‘unselected’ cohort), and on the basis of (2) classic clinicopathologic features, (3) clinical subtypes, (4) PAM50-based molecular intrinsic subtypes, and (5) individual PAM50 target genes. After a median follow-up of 7.2 years, in the unselected cohort (n=6,211) increasing exercise exposure was not associated with a reduction in the risk of recurrence (adjusted ptrend = 0.60) or breast cancer death (adjusted ptrend = 0.39). On the basis of clinicopathologic features, an exercise-associated reduction in breast cancer death was apparent for tumors <2 cm (HR: 0.50, 95% CI, 0.34 to 0.72), well / moderately differentiated tumors (HR: 0.63, 95% CI, 0.43 to 0.91), and ER-positive tumors (HR: 0.72, 95% CI, 0.53 to 0.97). Stratification by clinical subtype indicated that the ER⁺/PR⁺/HER2−/low-grade clinical subtype was preferentially responsive to exercise (recurrence: adjusted HR: 0.63, 95% CI, 0.45 to 0.88; breast cancer death: adjusted HR: 0.57, 95% CI, 0.37 to 0.86). The impact of exercise on cancer outcomes appears to differ as a function of pathologic and molecular features in early stage breast cancer.