Age, molecular subtypes and local therapy decision-making

The relationship between age and breast cancer subtype is complex: both impact risk of locoregional recurrence (LRR) and survival. Young patients frequently present with aggressive tumors but the increased risk imparted by young age appears to differ among breast cancer subtypes. Dramatic improvements in local control among young women with breast cancer of all tumor subtypes have been observed, likely attributable to improved local therapy strategies, improvements in adjuvant therapies and implementation of subtype-specific targeted therapies. In the light of these improvements in local control, accumulating evidence demonstrates that there is no difference in LRR or survival between breast conserving therapy (BCT) and mastectomy in young patients. An increased risk of LRR in triple-negative cancers is apparent; yet this increased risk of LRR is present following surgical treatment with both BCT and mastectomy and does not significantly differ by age. Also, contralateral breast cancer rates remain low for all age groups and, although the use of contralateral prophylactic mastectomy (CPM) has increased, there is no evidence that CPM improves survival. At the other end of the age spectrum, there is a growing body of evidence demonstrating a favorable interaction between older age and molecular subtype such that many older women with estrogen receptor positive breast cancer may be spared axillary staging and/or radiation therapy without a detrimental impact on survival. Thus for both age and subtype, it appears that the intrinsic biology is the strongest predictor of outcome. Tumor biology, and not age, should be the driver in local therapy decision-making.