- The human epidermal growth factor receptor 2 (HER2)-enriched subtype is the most common nonluminal tumor subtype based on expression patterns of 50 genes.
- This subtype predicts poorer PFS in response to everolimus in a retrospective analysis of hormone receptor (HR)+/HER2− patients with advanced breast cancer (aBCa) in the BOLERO-2 study.
Why this matters
- The findings suggest the importance of new clinical trials targeting nonluminal disease, especially the HER2-enriched subtype.
- Retrospective analysis of 261 tumors from BOLERO-2, which randomly assigned 724 patients with HR+/HER2− aBCa to everolimus or placebo in addition to exemestane.
- PAM50 genetic analysis identified intrinsic subtypes.
- Funding: Novartis; others.
- Nonluminal (vs luminal) subtypes, regardless of treatment, had a poorer median PFS (5.2 vs 6.7 months; P=.02).
- HER2-enriched tumor subtypes, which accounted for 21.5% of tumors, had the poorest median PFS vs the other 3 non-HER2-enriched subtypes (5.2 vs 6.2 months; adjusted HR [aHR], 1.53; P=.019).
- While patients with HER2-enriched tumors responded better to everolimus vs placebo (median PFS: 5.8 vs 4.1 months; aHR, 0.49; P=.034), the benefit was less than that of patients with non-HER2-enriched subtypes (8.7 vs 4.1 months; P<.0001>
- The interaction between HER-enriched tumors and everolimus benefit was nonsignificant (P=.433).
- Only 36.0% of BOLERO-2 population evaluated.