Recommendation of systemic adjuvant therapy and choice of optimal agents for 
early-stage breast cancer remains a challenge. Adjuvant therapy is indicated on 
the assumption of residual micrometastatic disease. Adjuvant assessment tools 
for prognosis and prediction of treatment benefit, including Adjuvant! Online, 
the St Gallen Consensus, Oncotype DX(®) and MammaPrint(®), aid clinical decision 
making. However, all of these tools have limitations that must be considered in 
their judicious application. Clinicopathological based tools are critically 
dependent on accurate, standardized measurement of parameters. Multigene tools 
are appealing for their objectivity and reproducibility, particularly regarding 
analysis of proliferation, but these approaches still overlook the biological 
heterogeneity within tumors evidenced by distinct cell subpopulations with 
different genomic patterns and function. The greatest treatment challenge 
remains for patients assessed as intermediate risk of relapse, a problem not 
overcome by multigene tools. Remarkable diversity in breast cancer dictates that 
adjuvant management must be biologically driven. Future identification of 
predictive biomarkers for specific chemotherapy sensitivity may allow targeted 
use of available agents, including anthracyclines, taxanes and DNA damaging 
agents. The presence of drug targets and targetable signaling pathways, rather 
than molecularly defined subgroups, may ultimately drive treatment decisions.