Christos Sotiriou, MD, PhD, Institute Jules Bordet, Brussels, Belgium, gives an overview of the history of molecular profiling in early stage breast cancer, highlighting the role of biomarkers in prognostication and key clinical trials. Prof. Sotiriou also comments on findings from the Phase III RxPONDER trial (NCT01272037) of endocrine therapy with or without chemotherapy in patients with HR+/HER2- breast cancer, and results from the Phase III TAILORx trial (NCT00310180) investigating hormone therapy with or without chemotherapy for women who have undergone surgery for node-negative breast cancer. This interview took place at the virtual European Society for Medical Oncology (ESMO) Breast Cancer Congress 2021.