Oncotype DX, PAM50, and MammaPrint are multigene tests that are being used 
clinically for early-stage breast cancer to predict recurrence risk and guide 
adjuvant chemotherapy decisions. These tests have been validated in multiple 
retrospective studies, and prospective clinical trials are in progress. The 
TAILORx trial uses the Oncotype DX recurrence score to assign estrogen 
receptor-positive (ER+), node-negative patients to chemotherapy plus hormonal 
therapy versus hormonal therapy alone. The RxPONDER (SWOG S1007) trial uses 
Oncotype DX in a similar approach but on node-positive patients, and it includes 
the PAM50 test as a secondary analysis. The MINDACT trial uses Mamma-Print and 
Adjuvant! Online for treatment arm assignments. MINDACT has very broad 
eligibility criteria and 2 secondary randomizations for selecting chemotherapy 
and hormonal therapy regimens. This article discusses how the latest results on 
cancer genome sequencing apply to early-stage breast cancer. Several hundred 
breast cancers have already undergone genome sequencing, and the somatic DNA 
changes found in the tumor, compared with the patient's normal DNA, have been 
identified. Higher rates of point mutations and chromosomal translocations are 
found in aromatase inhibitor-resistant ER+ cancers and in the basal-like and 
HER2-enriched breast cancer subtypes. Correlations of somatic mutations with 
neoadjuvant aromatase inhibitor response are discussed. Genome sequencing can 
potentially identify the molecular abnormalities that underlie the poor risk 
identified by multigene tests and provide potential new targets for therapy, but 
more clinical trials correlating clinical outcome and somatic DNA changes are 
needed.