Estrogen independent gene expression defines clinically relevant subgroups of estrogen receptor positive breast...

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.

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.

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.

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.