Background: Treatment of patients with luminal metastatic breast cancer (MBC) has become even more complex over the last few years as molecular profiling has begun to alter disease management. It is well accepted that MBC is not curable but is treatable. Today we are able to prolong progression-free survival and partly overall survival with targeted and more individual treatment strategies adjusted according to the molecular subtype. Summary: Genetic and genomic testing has become therapeutically relevant in luminal MBC and is therefore an integral component within the treatment spectrum. By now, germline testing of BRCA1 and BRCA2 and somatic testing for PIK3CA mutations are inevitable elements in disease management and the current state of the art in luminal MBC patients. Furthermore, testing of ESR1 resistance mutation, ERBB2 mutation, microsatellite instability, and neurotrophic tyrosine receptor kinase (NTRK) gene fusion (mainly in secretory breast cancer) has recently gained increasing attention. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities. The following review summarizes current developments in genetic and genomic testing in luminal MBC. Key Messages: In luminal MBC genomics have become an integral component within the spectrum of oncological treatment establishing novel therapeutic facilities. Further developments in treatment personalization adjusted according to the molecular subtype should become increasingly important in order to enhance the progress of de-escalation of chemotherapy in luminal MBC. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities.

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