- BACKGROUND: Human breast cancer represents a significantly heterogeneous disease. Global gene expression profiling measurements have been used to classify tumors into multiple molecular subtypes. The capacity to define subtypes of breast tumors provides a framework to enable improved understanding of the mechanisms of breast oncogenesis, as well as to provide opportunities for improved therapeutic intervention in patients. METHODS: We used publicly available gene expression profiling data to identify 'estrogen independent' genes in estrogen receptor alpha (ER+) breast tumors, and subsequently identified 6 subgroups of ER+breast tumors. RESULTS: Each of the 6 identified subgroups exhibited distinct clinical behaviors and biology. Patients whose tumors comprised subgroups 2,5&6 experienced excellent long-term survival, whereas those patients whose tumors belonged to subgroups 1&4 experienced much poorer survival. Breast tumor cell lines representative of the different subgroups responded to therapeutic compounds in accordance with their subgroup classification. CONCLUSIONS: These data support the existence of 6 distinct subgroups of ER+breast cancer and suggest that knowledge of the ER+subgroup status of patient samples have the potential to guide therapy choice.