Since both baseline and acquired alterations are potentially targetable (e.g., activating PIK3CA, ERBB2, KRAS, BRAF, FGFR1/2/3), longitudinal profiling throughout the course of care may provide additional treatment options, through combinatorial therapies or switching therapy regimens based on the evolving tumor landscape, to improve outcomes for patients with breast cancer. The gene discussed is PIK3CA; the disease is breast cancer.