Histological, molecular and functional subtypes of breast cancers

Abstract

Increased understanding of the molecular heterogeneity that is intrinsic to the various subtypes of breast cancer will likely shape the future of breast cancer diagnosis, prognosis, and treatment. Advances in the field over the last several decades have been remarkable and have clearly translated into better patient care as evidenced by the earlier detection, better prognosis, and new targeted therapies. There have been two recent advances in the breast cancer research field that have lead to paradigm shifts: first, the identification of intrinsic breast tumor subtypes, which has changed the way we think about breast cancer and second, the recent characterization of cancer stem cells (CSCs), which are suspected to be responsible for tumor initiation, recurrence and resistance to therapy, have opened new exciting avenues to think about breast cancer therapeutic strategies. While these advances constitute major paradigm shifts within the research realm, the clinical arena has yet to adopt and apply our understanding of the molecular basis of the disease to early diagnosis, prognosis and therapy of breast cancers. Here, we will review the current clinical approach to classification of breast cancers, newer molecular-based classification schemes, and potential future of biomarkers representing a functional classification of breast cancer.

Figure 1

Histological classification of breast cancer subtypes. This scheme, currently used by clinicians, categorizes the heterogeneity found in breast cancer based on architectural features and growth patterns. HPF: high power field.

Figure 2

Molecular classification of breast cancer. This classification is based on the intrinsic molecular subtypes of breast cancer identified by microarray analysis of patient tumor specimens.–

Figure 3

Functional classification of breast cancer. This scheme will classify breast cancer based on the tumor initiating cells. Currently there are two proposed hypothesis: (A) either the heterogeneity seen in breast cancer arises from distinct mammary stem/progenitor cells at various levels within the mammary stem cell hierarchy or, (B) breast cancer heterogeneity is the result of a single mammary stem/progenitor cell being transformed by various oncogenes which give rise to various types of cancer.