From Immunohistochemistry to New Digital Ecosystems: A State-of-the-Art Biomarker Review for Precision Breast Cancer Medicine.

Breast cancers represent complex ecosystem-like networks of malignant cells and their associated microenvironment. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are biomarkers ubiquitous to clinical practice in evaluating prognosis and predicting response to therapy. Recent feats in breast cancer have led to a new digital era, and advanced clinical trials have resulted in a growing number of personalized therapies with corresponding biomarkers. In this state-of-the-art review, we included the latest 10-year updated recommendations for ER, PR, and HER2, along with the most salient information on tumor-infiltrating lymphocytes (TILs), Ki-67, PD-L1, and several prognostic/predictive biomarkers at genomic, transcriptomic, and proteomic levels recently developed for selection and optimization of breast cancer treatment. Looking forward, the multi-omic landscape of the tumor ecosystem could be integrated with computational findings from whole slide images and radiomics in predictive machine learning (ML) models. These are new digital ecosystems on the road to precision breast cancer medicine.