Aberrations in the cell cycle machinery or abnormal signaling via the PI3K/Akt/mTOR intracellular signaling pathway, are proposed mechanisms by which this resistance can occur.2 Clinical trials investigating relevant combinations have led to the United States (US) Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval of new treatment combinations for patients with advanced breast cancer in recent years.3–5 These therapeutic advances are welcome and will no doubt improve outcomes for many patients with advanced breast cancer. The gene discussed is AKT1; the disease is breast carcinoma.