Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona; Facultat de Medicina i Ciéncies de la Salut, Universitat de Barcelona, Barcelona, Spain.
Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona; Facultat de Medicina i Ciéncies de la Salut, Universitat de Barcelona, Barcelona, Spain; Breast Oncology Program, Dana-Farber Cancer Institute, Boston, USA.
ESMO Open. 2023 Jun;8(3):101214. doi: 10.1016/j.esmoop.2023.101214. Epub 2023 Apr 17.
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).
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. Threshold for significance was set at P < 0.05. The study was registered in PROSPERO (ID: CRD42021255769).
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 = 61%], independently of clinical HER2 status [P (P) = 0.16], systemic treatment (P = 0.96) and menopausal status (P = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I = 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 = 0.01; OS P = 0.005). Sensitivity analyses supported the main result. No publication bias was observed.
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.
在激素受体阳性（HoR+）乳腺癌（BC）中，基因表达分析可识别出管腔 A（LumA）、管腔 B（LumB）、人表皮生长因子受体 2（HER2）富集（HER2-E）、基底样（BL）固有亚型和正常样组。这种分类在早期 HoR+BC 中具有明确的预后价值。在这里，我们进行了一项试验水平的荟萃分析，以确定转移性 BC（MBC）中亚型的预后能力。
我们系统地回顾了所有可用的 HoR+MBC 前瞻性 II/III 期试验，其中评估了亚型。主要终点是与非 LumA 相比，LumA 亚型的无进展生存期（PFS）/进展时间（TTP）。次要终点是根据治疗、绝经状态和 HER2 状态以及总生存期（OS），每个亚型的 PFS/TTP。应用随机效应模型，并通过 Cochran's Q 和 I 评估异质性。显著性阈值设为 P<0.05。该研究已在 PROSPERO（ID：CRD42021255769）中注册。
共纳入 7 项研究（2536 例患者）。非 LumA 占 55.2%，与 LumA 相比，PFS/TTP 更差[风险比（HR）1.77，P<0.001，I=61%]，独立于临床 HER2 状态[P（P）=0.16]、全身治疗（P=0.96）和绝经状态（P=0.12）。非 LumA 肿瘤的 OS 也较差（HR 2.00，P<0.001，I=65%），LumB（PFS/TTP HR 1.46；OS HR 1.41）、HER2-E（PFS/TTP HR 2.39；OS HR 2.08）和 BL（PFS/TTP HR 2.67；OS HR 3.26）的结局差异有统计学意义（PFS/TTP P=0.01；OS P=0.005）。敏感性分析支持主要结果。未观察到发表偏倚。
在 HoR+MBC 中，非 LumA 疾病与 LumA 相比，PFS/TTP 和 OS 更差，独立于 HER2、治疗和绝经状态。未来 HoR+MBC 的临床试验应考虑这种具有临床意义的生物学分类。
