After a promising phase II trial on temsirolimus 30 mg daily for 5 days every 2 weeks and letrozole 2.5 mg daily versus letrozole alone, in postmenopausal women with recurrent or metastatic disease [10], the combination treatment was investigated in the phase III HORIZON, in postmenopausal hormone receptor positive women not treated with AI, with advanced or metastatic disease. The gene discussed is NR4A1; the disease is metastatic neoplasm.