Differential Responses to Hormone Therapy Among ER+/PR+/HER2‐ Breast Cancers That Differentially Express the Estrogen Response Signature

ER+/PR+/HER2‐ breast cancers are frequently associated with good outcomes, but some patients experience disease progression/recurrence. We examined responses to hormone therapy (HT) in 182 ER+/PR+/HER2‐ breast cancers (with known molecular subtype) that differentially express a 583‐gene estrogen response signature (ERS). Overall, 13/33 (39%) patients treated with HT relapsed versus 77/149 (52%) untreated patients. 142 ER+/PR+/HER2‐ breast cancers are ERS+ (27% relapse with HT, 48% untreated relapse), and 40 ER+/PR+/HER2‐ breast cancers are ERS‐ (100% relapse with HT, 62% untreated relapse). Kaplan‐Meier analysis revealed a significant improvement in relapse‐free survival among ERS+ ER+/PR+/HER2‐ breast cancers that received HT versus untreated (P=0.0489). ERS+ ER+/PR+/HER2‐ Luminal A breast cancers benefit from HT – 5/19 (26%) treated relapsed versus 36/75 (48%) untreated relapsed. ERS+ ER+/PR+/HER2‐ Luminal B (LumB) breast cancers show less benefit from HT – 1/3 (33%) treated relapse versus 12/29 (41%) untreated relapse. Any HT benefit observed is lost among ERS‐ ER+/PR+/HER2‐ LumB breast cancers – 5/5 (100%) treated relapse versus 10/17 (59%) untreated relapse. ER+/PR+/HER2‐ HER2‐enriched breast cancers do not benefit from HT – Over 50% relapse irrespective of ERS or HT status. Despite small numbers, ERS+ ER+/PR+/HER2‐ Basal‐like and Claudin‐low breast cancers appear to show benefit from HT – 0/3 (0%) treated relapse versus 4/6 (67%) untreated relapse. Most molecular subtypes of ERS+ ER+/PR+/HER2‐ breast cancer benefit from HT.