Molecular Classification Predicts Outcome Among Patients With ER+/PR+/HER2‐ Breast Cancers

ER+/PR+/HER2‐ breast cancers are frequently associated with good outcomes, but some patients experience progression/recurrence. We examined molecular subtypes of ER+/PR+/HER2‐ breast cancer to determine if molecular classification predicts patient outcome. Evaluation of gene expression patterns for 205 ER+/PR+/HER2‐ breast cancers enabled assignment of molecular subtype: 49% Luminal A (LumA), 27% Luminal B (LumB), 6% HER2‐enriched (HER2+), 3% Basal‐like (BL), 7% Claudin‐low (CL), and 8% Normal‐like (NL). Overall, 99/205 (48%) ER+/PR+/HER2‐ patients developed metastatic disease: 44/100 (44%) LumA, 29/55 (53%) LumB, 6/13 (46%) HER2+, 5/7 (71%) BL, 8/14 (57%) CL, and 7/16 (44%) NL. Among ER+/PR+/HER2‐ breast cancers, the average time to relapse for BL (27 months), HER2+ (25 months), and LumB (27 months) was significantly shorter than LumA (37 months). Kaplan‐Meier survival analysis did not reveal a significant trend between ER+/PR+/HER2‐ LumA versus LumB, HER2+, or CL subtypes, but the ER+/PR+/HER2‐ BL subset showed significantly worse relapse‐free survival (RFS) than the ER+/PR+/HER2‐ LumA subset (P=0.0444). Patients with ER+/PR+/HER2‐ BL breast cancer demonstrate 29% RFS at 50 months versus 56% at 100 months for ER+/PR+/HER2‐ LumA. Relapse among ER+/PR+/HER2‐ LumA breast cancers typically involved bone metastasis (80%), while ER+/PR+/HER2‐ BL breast cancers frequently metastasize to brain or lung (80%). Expression of gene signatures associated with aggressive molecular subtypes of breast cancer predict more aggressive disease among ER+/PR+/HER2‐ breast cancers.