1. Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis.
- Author
-
Schettini F, Martínez-Sáez O, Falato C, De Santo I, Conte B, Garcia-Fructuoso I, Gomez-Bravo R, Seguí E, Chic N, Brasó-Maristany F, Paré L, Vidal M, Adamo B, Muñoz M, Pascual T, Ciruelos E, Perou CM, Carey LA, and Prat A
- Subjects
- Humans, Female, Prognosis, Prospective Studies, Proportional Hazards Models, Breast Neoplasms drug therapy, Antineoplastic Agents therapeutic use
- Abstract
Background: In hormone receptor-positive (HoR+) breast cancer (BC), gene expression analysis identifies luminal A (LumA), luminal B (LumB), human epidermal growth factor receptor 2 (HER2)-enriched (HER2-E), basal-like (BL) intrinsic subtypes and a normal-like group. This classification has an established prognostic value in early-stage HoR+ BC. Here, we carried out a trial-level meta-analysis to determine the prognostic ability of subtypes in metastatic BC (MBC)., Materials and Methods: We systematically reviewed all the available prospective phase II/III trials in HoR+ MBC where subtype was assessed. The primary endpoint was progression-free survival (PFS)/time to progression (TTP) of the LumA subtype compared to non-LumA. Secondary endpoints were PFS/TTP of each individual subtype, according to treatment, menopausal and HER2 status and overall survival (OS). The random-effect model was applied, and heterogeneity assessed through Cochran's Q and I
2 . Threshold for significance was set at P < 0.05. The study was registered in PROSPERO (ID: CRD42021255769)., Results: Seven studies were included (2536 patients). Non-LumA represented 55.2% and was associated with worse PFS/TTP than LumA [hazard ratio (HR) 1.77, P < 0.001, I2 = 61%], independently of clinical HER2 status [Psubgroup difference (Psub ) = 0.16], systemic treatment (Psub = 0.96) and menopausal status (Psub = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I2 = 65%), with significantly different outcomes for LumB (PFS/TTP HR 1.46; OS HR 1.41), HER2-E (PFS/TTP HR 2.39; OS HR 2.08) and BL (PFS/TTP HR 2.67; OS HR 3.26), separately (PFS/TTP Psub = 0.01; OS Psub = 0.005). Sensitivity analyses supported the main result. No publication bias was observed., Conclusions: In HoR+ MBC, non-LumA disease is associated with poorer PFS/TTP and OS than LumA, independently of HER2, treatment and menopausal status. Future trials in HoR+ MBC should consider this clinically relevant biological classification., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF