In this context the phase III, multicenter, randomized ALPHABET trial is investigating the efficacy and safety of alpelisib + trastuzumab ± fulvestrant versus trastuzumab + chemotherapy in patients with HER2+/PIK3CA-mutated advanced breast cancer progressing to a previous anti-HER2 treatment (NCT05063786). The gene discussed is PIK3CA; the disease is breast carcinoma.