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Breast cancer affects 12% of females in the United States and is the leading cause of cancer death in the female population. Personalized therapy is being used in clinical practice to treat breast cancer based on tumor molecular profiling, which can be obtained from tissue biopsy or plasma liquid biopsy as circulating tumor deoxyribonucleic acid (ctDNA). The available ctDNA tests provide a non-invasive way to monitor the cancer genome in a real-time manner.  In this case report, a 38-year-old female with recurrent estrogen receptor (ER) positive breast cancer is treated with letrozole, everolimus, and palbociclib. The drugs target the hormonal signaling pathway, phosphoinositide 3-kinase (PI3K)-RAC-alpha serine/threonine-protein kinase (AKT) pathway, and cyclin D1 (CCND1)-CDK4/6 pathway, based on the patient’s estrogen-receptor-positive (ER+) disease and phosphatidylinositol -4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ) mutation, as well as  PIK3CA  and  CCND1    amplification. After 11 months of treatment, retinoblastoma protein transcriptional corepressor 1 ( RB1 ) mutation was caught in ctDNA, which suggests an acquired resistance to palbociclib. Pazopanib was then used instead of palbociclib, targeting the  fibroblast growth factor 3/4/19 (  FGF3/4/19  )  amplification that was initially observed in her molecular profiling. Trametinib was also suggested recently due to the increasing allele frequency of B-Raf proto-oncogene, serine/threonine kinase ( BRAF ) mutation in ctDNA, following the treatment of letrozole + everolimus + pazopanib. The patient has no evidence of disease after five months of treatment initiation and has remained disease-free for over 16 months.  In conclusion, the analysis of ctDNA is an effective way to monitor the real-time changes in a patient's tumor genome, which is a great supplement to the molecular profile from the tissue biopsy. The combination of these two tests provides an efficient strategy to make more informed treatment decisions, which greatly adapt along disease development. 

Utilizing Tumor and Plasma Liquid Biopsy in Treatment Decision Making for an Estrogen Receptor-Positive Advanced Breast Cancer Patient