Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis

Schettini, F; Martinez-Saez, O; Falato, C; De Santo, I; Conte, B; Garcia-Fructuoso, I; Gomez-Bravo, R; Segui, E; Chic, N; Braso-Maristany, F; Pare, L; Vidal, M; Adamo, B; Munoz, M; Pascual, T; Ciruelos, E; Perou, CM; Carey, LA; Prat, A

Author(s): Schettini, F; Martinez-Saez, O; Falato, C; De Santo, I; Conte, B; Garcia-Fructuoso, I; Gomez-Bravo, R; Segui, E; Chic, N; Braso-Maristany, F; Pare, L; Vidal, M; Adamo, B; Munoz, M; Pascual, T; Ciruelos, E; Perou, CM; Carey, LA; Prat, A;
Details: Publication Year 2023-04-17,Volume 8,Issue #3,Page 101214
Journal Title: ESMO Open
Publication Type: Research article
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, I(2) = 61%], independently of clinical HER2 status [P(subgroup difference) (P(sub)) = 0.16], systemic treatment (P(sub) = 0.96) and menopausal status (P(sub) = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I(2) = 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 P(sub) = 0.01; OS P(sub) = 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.
Publisher: Elsevier
Keywords: breast cancer; hormone receptors; intrinsic subtypes; metastatic; prognosis
Department(s): Laboratory Research
PubMed ID: 37075698
Publisher's Version: https://doi.org/10.1016/j.esmoop.2023.101214
Open Access at Publisher's Site: https://doi.org/10.1016/j.esmoop.2023.101214
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-08-07 07:16:15

Last Modified: 2023-08-07 07:17:40