For example, the phase 3 SONIA trial [33] has challenged the paradigm of HR+/HER2- metastatic BC treatment after showing that first-line treatment with ET and CDK4/6i, followed by fulvestrant, did not improve PFS nor OS in comparison to second-line CDK4/6 inhibition plus fulvestrant after first-line ET. The gene discussed is ERBB2; the disease is breast cancer.