Schiavone Maria Luisa, Scarpitta Rosa, Ravera Francesco, Bleve Sara, Reduzzi Carolina, Di Cocco Federico, Dameri Martina, Zoppoli Gabriele, Naccarato Antonio Giuseppe, Nuzzo Pier Vitale, Cristofanilli Massimo, Fanelli Giuseppe Nicolò, Scatena Cristian
Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126, Pisa, Italy.
Department of Internal Medicine and Medical Specialties, University of Genova, 16132, Genova, Italy.
J Liq Biopsy. 2025 Jul 16;9:100312. doi: 10.1016/j.jlb.2025.100312. eCollection 2025 Sep.
Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death among women worldwide. It represents a heterogeneous group of diseases with distinct morphological, immunophenotypic, and molecular profiles, which significantly impact clinical behavior and therapeutic response. Moreover, under treatment pressure, tumor cells may undergo molecular changes and phenotypic plasticity, leading to resistance and therapeutic failure. Although tissue biopsy remains the gold standard for diagnosis and molecular characterization, it has several limitations, including invasiveness, sampling bias, and the inability to dynamically capture tumor evolution over time. Hence, a non-invasive and repeatable approach capable of real-time monitoring is increasingly needed. Liquid biopsy (LB), through the analysis of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), has emerged as a powerful tool to complement tissue biopsy. It allows for longitudinal assessment of tumor burden, detection of minimal residual disease, and identification of molecular alterations relevant to targeted therapies. Despite promising results, the integration of LB into clinical practice is still limited by methodological heterogeneity, standardization gaps, and regulatory issues. Nonetheless, LB represents a key advancement toward precision oncology and may become essential in the personalized management of BC patients. In this review, we explore the current applications, benefits, and technical limitations of LB in different BC settings. We provide a comprehensive overview of the biological and clinical significance of CTCs and ctDNA, emphasizing their diagnostic, prognostic, and predictive roles. Finally, we present an updated summary of ongoing clinical trials that incorporate LB for clinical decision-making.
乳腺癌（BC）是全球女性中最常见的癌症，也是癌症相关死亡的主要原因。它是一组异质性疾病，具有不同的形态、免疫表型和分子特征，这对临床行为和治疗反应有显著影响。此外，在治疗压力下，肿瘤细胞可能会发生分子变化和表型可塑性，导致耐药性和治疗失败。尽管组织活检仍然是诊断和分子特征分析的金标准，但它有几个局限性，包括侵入性、采样偏差以及无法动态捕捉肿瘤随时间的演变。因此，越来越需要一种能够实时监测的非侵入性且可重复的方法。液体活检（LB）通过分析循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA），已成为补充组织活检的有力工具。它允许对肿瘤负荷进行纵向评估、检测微小残留病以及识别与靶向治疗相关的分子改变。尽管取得了令人鼓舞的结果，但LB在临床实践中的整合仍受到方法学异质性、标准化差距和监管问题的限制。尽管如此，LB代表了精准肿瘤学的一项关键进展，可能在BC患者的个性化管理中变得至关重要。在本综述中，我们探讨了LB在不同BC情况下的当前应用、益处和技术局限性。我们全面概述了CTC和ctDNA的生物学和临床意义，强调了它们的诊断、预后和预测作用。最后，我们提供了纳入LB用于临床决策的正在进行的临床试验的最新总结。
