The clinical outcomes of breast cancer patients have been significantly improved in recent years, yet many breast cancer patients experience cancer relapse or drug-induced toxicities. Adverse outcomes result from intrinsic tumor biology, treatment-induced resistance traits, as well as host factors such as impaired drug metabolism and endogenous ligands interfering with drug–target action. My research focuses on mitigating clinical resistance of hormone-receptor positive breast cancer treatment, which due to its high prevalence holds high chances to reduce overall death burden. This includes pharmacogenomic prediction of impaired drug exposure (e.g. due to genetic polymorphism or drug-target interactions), genome-wide searches of novel treatment-predictive features such as the immune response in hormone-sensitive tumors, tumor cell model research for estrogen-receptor signaling and linked resistance pathways, and the molecular profiling of breast tumors based on their transcriptome and somatic mutation landscape. Prediction tools such as liquid-biopsy based detection of circulating tumor markers and the employment of ex-vivo microtumor models (organoids) will be used to translate novel diagnostic markers and/or multimodal drug target approaches into the clinic.