Breast cancer heterogeneity in primary and metastatic disease

Abstract

The term 'breast cancer' describes a heterogeneous collection of neoplasms arising from the mammary epithelium. Tumors in different patients display diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Current histopathological classification systems aim to categorise tumors into subgroups to inform patient management decisions, but the diversity within subgroups is considerable. Molecular analyses such as gene expression profiling, and more recently, massively parallel sequencing technologies, have been employed to increase the degree of resolution in breast cancer taxonomies. It will take time for this information to be translated into the clinic. Sequencing projects have also been instrumental in revealing the true extent of intratumoral heterogeneity: three-dimensional variability in the genetic, phenotypic, cellular and microenvironmental constitution of individual tumors. This variability underlies clinical problems such as metastasis and drug resistance, and will present additional challenges as breast cancer diagnostics evolves to include higher resolution molecular analyses. Intratumoral heterogeneity will need to be carefully considered as we move towards more personalized models of breast cancer patient management.