Growing evidence supports the notion that intrinsic subtypes (ISs) may offer both predictive and prognostic significance within HER2+ BC, particularly in the context of anti-HER2 therapies.10, 11, 12 Our analysis in POETIC confirmed the hypothesis that pre-treatment HER2-enriched (HER2-E) IS predicts an early poor biological response to AI and a higher risk of relapse in ER+/HER2+ BC when treated with AI alone.13 The gene discussed is ESR1; the disease is breast cancer.