Breast Cancer Adjuvant Therapy: Time to Consider Its Time-Dependent Effects

Breast cancer is a chronic and heterogeneous disease that may recur many years after initial diagnosis and treatment.1 This has important implications for the practicing oncologist. For instance, an early effect of adjuvant treatment may diminish over time after cessation of therapy, or, alternatively, there may exist a lag time before some treatment effects become pronounced. Indeed, the risk of breast cancer recurrence and death (hazard rate) varies over time (ie, is nonproportional) according to prognostic and predictive factors (Figs 1 and ​and2;2; Table 1).6,13 The hazard curve for breast cancer death peaks between 2 and 3 years after initial diagnosis and then declines sharply, suggesting that the biologic mechanisms responsible for early and late cancer-specific events are fundamentally different. Thus the early and late effects of adjuvant therapy may vary accordingly.