LumA or B ER+ BC is classically treated using ER (ESR1)-directed endocrine therapies—aromatase inhibitors (AIs) or the selective ER modulator (SERM) tamoxifen in the first-line setting, and the selective ER degrader (SERD) fulvestrant or the combination of endocrine with CDK4/6 inhibitor (CDK4/6i) palbociclib or ribociclib, which were tested in the PALOMA (4) and MONALEESA (5) trials, or CDK4/6i abemaciclib monotherapy (MONARCH (6) study), in the first-line and endocrine refractory second-line settings (7, 8). The gene discussed is ESR1; the disease is breast cancer.