Fusco Nicola, Malapelle Umberto
Division of Pathology, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Italy.
Department of Public Health, Federico II University of Naples, Naples 80131, Italy.
Crit Rev Oncol Hematol. 2025 Mar;207:104626. doi: 10.1016/j.critrevonc.2025.104626. Epub 2025 Feb 3.
Molecular alterations in the Phosphoinositide 3-kinase (PI3K) pathway are key drivers of tumorigenesis and progression in hormone receptor-positive, HER2-negative (HR+/HER2 -) metastatic breast cancer (MBC). These genomic changes are actionable through targeted therapeutic agents. In particular, access to these therapies depends on accurate molecular testing of PIK3CA, AKT1, and PTEN. Next-generation sequencing (NGS) has emerged as a transformative diagnostic tool, offering a comprehensive analysis of PI3K pathway alterations while concurrently evaluating other actionable markers, such as ESR1 and BRCA. Acknowledging its clinical importance, the European Society for Medical Oncology (ESMO) recommends NGS of tumor or plasma samples as the standard of care for patients with HR+ /HER2 - MBC. Although resource-intensive, NGS represents a significant advancement in MBC diagnostics, ensuring that therapeutic decisions are informed by a detailed and multidimensional molecular profile. This review highlights the capabilities of NGS for PI3K pathway testing in HR+ /HER2 - MBC, with a particular focus on the spectrum of PTEN alterations.
磷脂酰肌醇3激酶（PI3K）通路的分子改变是激素受体阳性、人表皮生长因子受体2阴性（HR+/HER2-）转移性乳腺癌（MBC）肿瘤发生和进展的关键驱动因素。这些基因组变化可通过靶向治疗药物来应对。特别是，获得这些治疗取决于对PIK3CA、AKT1和PTEN进行准确的分子检测。新一代测序（NGS）已成为一种变革性的诊断工具，它能对PI3K通路改变进行全面分析，同时评估其他可采取行动的标志物，如ESR1和BRCA。认识到其临床重要性，欧洲医学肿瘤学会（ESMO）推荐对肿瘤或血浆样本进行NGS检测，作为HR+/HER2-MBC患者的标准治疗方案。尽管NGS检测资源消耗大，但它代表了MBC诊断的重大进展，确保治疗决策基于详细的多维分子图谱。本综述重点介绍了NGS在HR+/HER2-MBC中对PI3K通路检测的能力，尤其关注PTEN改变的范围。
