Title:Targeted Pathways in Breast Cancer: Molecular and Protein Markers Guiding Therapeutic Decisions
VOLUME: 7 ISSUE: 1
Author(s):Helen P. Kourea, Vassiliki Zolota and Chrisoula D. Scopa
Affiliation:Department of Pathology, School of Medicine, University of Patras, Patras, 26500, Greece.
Keywords:Biomarkers, Breast carcinoma, ER/PgR, HER2, Ki67, miRNAs, molecular signatures, prognostic/predictive, TILs.
Abstract:Breast carcinoma is currently considered as a group of diseases, differing not only in histopathologic phenotype,
as indicated by histologic type and grade, but also in their protein, genetic and epigenetic molecular profile. The
standard of care indicates that the core information for patient management includes data on Estrogen Receptor (ER), Progesterone
Receptor (PgR) and Human Epidermal Growth Factor Receptor 2 (HER2), while there is an emerging role for
the proliferation marker Ki67. These indices can be provided even in low resource settings and are indispensable for
prognostication and therapeutic patient management. With the progress in molecular and translational research, there is a
growing body of information on the molecular subtypes of breast carcinoma and their significance, and multigene signature
assays are used to dictate prognosis and guide therapeutics in high resource settings. In addition, several cellular
pathways involved in tumor growth and spread are dissected and targeted in clinical trials. Among these are the p53, RB,
PI3K/Akt/mTOR and Ras/MAPK pathways, alterations associated with genetic instability and epigenetic alterations including
histone methylation and acetylation, DNA methylation and microRNAs expression. The tumor immune microenvironment,
including the tumor infiltrating lymphocytes (TILs) is attracting significant research interest. This review
summarizes the mechanisms of function of the above factors in breast tumorigenesis with emphasis on their prognostic
and predictive value and their use as therapeutic targets.
