Node-negative breast cancer is a prevalent form of the disease worldwide, 
particularly in regions with rigorous screening and disease awareness efforts. 
Although there is a common biology between node-negative and node-positive 
breast tumors, it is still important to specifically address risk assessment and 
predictive factors in node-negative breast cancer. The relative risks and 
benefits are more pronounced in these patients, but there is no single 
prognostic factor available for deciding whether to administer chemotherapy and 
selecting the best adjuvant chemotherapy regimen. In the absence of universal 
predictive factors, the trend is to give chemotherapy to all patients to ensure 
the highest possibility for cure. Tumor grade is important in that it is 
predictive of risk over time, but lacks standardization. Adjuvant! Online, a 
web-based algorithm, is also used to guide treatment decisions. Recently, the 
urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 
type 1 (PAI-1) biomarkers have been used to determine disease risk and, 
consequently, determine whether or not chemotherapy is needed. However, the 
assay requires a fresh-frozen tissue sample, which is not always feasible. The 
oncotype DX® genomic assay has also been used to help prognosis estimation and 
treatment decisions. It is currently under evaluation in conjunction with the 
uPA/PAI-1 assay in the Plan B trial. The question that remains in adjuvant 
chemotherapy today for patients with node-negative disease is proper patient 
selection. Node-negative breast cancer does not automatically suggest a good 
prognosis, or the preclusion of chemotherapy benefits, and additional biomarkers 
are needed to help identify patients who do benefit from chemotherapy.