Objective: To examine and summarize the most discussed molecular targets for prognosis prediction in all histological subtypes of breast cancer.

Materials and Methods: The contemporary view on breast cancer pathology as heterogeneous disease has changed the therapeutic landscape from a “one size fits all” to a subtype specific treatment approach. We conducted a wide literature review in order to simplify the various findings associated with breast cancer molecular targets and the possible routine clinical implications in the future.

Results: The four intrinsic molecular subtypes of breast cancer are luminal A, luminal B, HER2/Neu-enriched and basal-like, with each subtype associated with a specific expression profile. Additionally, there are critical differences among the four molecular subtypes with regard to incidence, response to treatment, disease progression, survival, and imaging features: luminal A tumors have the most favorable prognosis of all breast cancer subtypes, whereas luminal B, HER2/Neu-enriched, and basal-like tumors have poorer clinical outcomes. Additionally, identification of expression-based tumor profiles most/least likely to respond to chemotherapy is changing the landscape of medical oncology.

Conclusions: Despite the significant prognostic improvements gained using current “individualized” therapeutic approaches, not all patients benefit as there are deeper sub-classes within the intrinsic subtypes which alter treatment responses. Thus, additional gene expression profiling of each subtype is essential in providing information about more accurate behavior of the different breast tumors, thus offering hope for an even more specific precision oncology. Such potential markers must not only demonstrate analytical and clinical validity along with clinical utility, but also provide wide availability and reproducibility.