The Effect of Local Therapy on Breast Cancer Mortality: Is There an Age-Interaction?

There are no randomized trials comparing local therapy versus no therapy in patients with primary breast cancer, as such trials would be deemed unethical. Thus, the impact of local therapy on breast cancer mortality is poorly understood. However, an overview of clinical trials comparing various permutations in the local therapy of breast cancer suggests that inadequate local therapy increases the risk of local recurrences, and thereby increases breast cancer mortality. Yet, age-interactions are commonly reported in studies that have examined the etiology, prognosis, and treatment of breast cancer, and might be associated with the effect of local therapy as well. Moreover, the effect of local therapy on breast cancer mortality might be time-dependent. In cohorts of women with high-risk tumors (predominantly younger women) local therapy may adversely (but only transiently) perturb the natural history of breast cancer. In contrast, such an effect is not evident in cohorts of women with low-risk tumors (predominantly older women). For both groups of patients, local therapy appears to ultimately have a beneficial effect in reducing breast cancer mortality, but in patients with low-risk tumors the benefit is immediate, while in patients with high-risk tumors it is delayed. Evidence for such an age-interaction is derived from comparison of the breast cancer hazard curves in women with high-risk and low-risk tumors, and analysis of the mammography screening trials. Neo-adjuvant systemic therapy may eventually prove useful in modulating the effects of local therapy.