Combined analyses of the PIK3CA mutational status in ctDNA, CTCs, and tdEVs using real-time PCRs (RT-PCR) and next generation sequencing (NGS) have shown that the targeting of these genes in HR+/HER2− metastatic BC has significant benefits after the occurrence of endocrine therapy resistance through the modulation of the PI3K/AKT/mTOR signaling pathway [150]. The gene discussed is PIK3CA; the disease is breast cancer.