Centre of Circulating Tumour Cell Diagnostics and Research, Ingham Institute of Applied Medical Research, Liverpool, NSW, Australia.
School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
Front Endocrinol (Lausanne). 2022 Jun 17;13:895729. doi: 10.3389/fendo.2022.895729. eCollection 2022.
Up to 80% of breast cancers (BCa) are estrogen receptor positive and current treatments target the estrogen receptor (endocrine therapies) and/or CDK4/6 (CDK4/6 inhibitors). encodes the protein cyclin D1, responsible for regulation of G1 to S phase transition in the cell cycle. amplification is common in BCa and contributes to increased cyclin D1 expression. As there are signalling interactions between cyclin D1 and the estrogen receptor, understanding the impact of amplification on estrogen receptor positive patients' disease outcomes, is vital. This review aims to evaluate amplification as a prognostic and predictive biomarker in BCa.
Publications were retrieved from the databases: PubMed, MEDLINE, Embase and Cochrane library. Exclusion criteria were duplication, publication type, non-English language, and animal studies, not BCa, male BCa, premenopausal BCa, cohort size <35, amplification not reported. Publications with cohort duplication, and inadequate recurrence free survival (RFS) and overall survival (OS) data, were also excluded. Included publications were assessed for Risk of Bias (RoB) using the Quality In Prognosis Studies tool. Statistical analyses (Inverse Variance and Mantel-Haenszel) were performed in Review Manager. The PROSPERO registration number is [CRD42020208179].
amplification was significantly associated with positive estrogen receptor status (OR:1.70, 95% CI:1.19-2.43, p = 0.004) and cyclin D1 overexpression (OR: 5.64, 95% CI: 2.32-13.74, p=0.0001). amplification was significantly associated with shorter RFS (OR: 1.64, 95% CI: 1.13-2.38, p = 0.009), and OS (OR: 1.51, 95% CI: 1.19-1.92, p = 0.0008) after removal of studies with a high RoB. In endocrine therapy treated patients specifically, amplification predicted shorter RFS (HR: 2.59, 95% CI: 1.96-3.41, p < 0.00001) and OS (HR: 1.59, 95% CI: 1.00-2.49, p = 0.05) also after removal of studies with a high RoB.
While a lack of standardised approach for the detection of amplification is to be considered as a limitation, amplification was found to be prognostic of shorter RFS and OS in BCa. amplification is also predictive of reduced RFS and OS in endocrine therapy treated patients specifically. With standardised methods and cut offs for the detection of amplification, amplification would have potential as a predictive biomarker in breast cancer patients.
https://www.crd.york.ac.uk/prospero/, identifier CRD42020208179.
多达 80%的乳腺癌（BCa）是雌激素受体阳性的，目前的治疗方法针对雌激素受体（内分泌治疗）和/或 CDK4/6（CDK4/6 抑制剂）。 编码蛋白 cyclin D1，负责细胞周期中 G1 到 S 期的过渡。 在 BCa 中常见扩增，并导致 cyclin D1 表达增加。由于 cyclin D1 和雌激素受体之间存在信号相互作用，了解 扩增对雌激素受体阳性患者疾病结局的影响至关重要。本综述旨在评估 扩增作为 BCa 的预后和预测生物标志物。
从数据库 PubMed、MEDLINE、Embase 和 Cochrane library 中检索出版物。排除标准为重复出版物、出版类型、非英语语言、 以及动物研究、非 BCa、男性 BCa、绝经前 BCa、队列规模 <35、未报告 扩增。还排除了具有队列重复且缺乏足够的无复发生存率（RFS）和总生存率（OS）数据的出版物。使用预后研究质量评估工具（Quality In Prognosis Studies tool）评估纳入的出版物的风险偏倚（RoB）。在 Review Manager 中进行统计分析（Inverse Variance 和 Mantel-Haenszel）。PROSPERO 注册号为 [CRD42020208179]。
扩增与阳性雌激素受体状态显著相关（OR：1.70，95%CI：1.19-2.43，p = 0.004）和 cyclin D1 过表达（OR：5.64，95%CI：2.32-13.74，p=0.0001）。 扩增与 RFS 较短显著相关（OR：1.64，95%CI：1.13-2.38，p = 0.009）和 OS 较短显著相关（OR：1.51，95%CI：1.19-1.92，p = 0.0008），去除 RoB 较高的研究后。在专门接受内分泌治疗的患者中， 扩增预测 RFS 较短（HR：2.59，95%CI：1.96-3.41，p < 0.00001）和 OS 较短（HR：1.59，95%CI：1.00-2.49，p = 0.05），去除 RoB 较高的研究后也是如此。
尽管缺乏用于检测 扩增的标准化方法被认为是一个限制，但 扩增被发现是 BCa 中 RFS 和 OS 较短的预后因素。 扩增也是内分泌治疗患者 RFS 和 OS 较短的预测因素。通过标准化方法和检测 扩增的截止值， 扩增有可能成为乳腺癌患者的预测生物标志物。
https://www.crd.york.ac.uk/prospero/，标识符 CRD42020208179。
