Giordano Guido, Griguolo Gaia, Landriscina Matteo, Meattini Icro, Carbone Francesco, Leone Augusto, Del Re Marzia, Fogli Stefano, Danesi Romano, Colamaria Antonio, Dieci Maria Vittoria
Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences - Policlinico Riuniti, University of Foggia, Foggia 71122, Italy.
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova 35128, Italy; Division of Oncology 2, Veneto Institute of Oncology IOV - IRCCS, Padova 35128, Italy.
Crit Rev Oncol Hematol. 2023 Dec;192:104185. doi: 10.1016/j.critrevonc.2023.104185. Epub 2023 Oct 18.
About 30-50 % of stage IV HER2+ breast cancers (BC) will present brain metastases (BMs). Their management is based on both local treatment and systemic therapy. Despite therapeutic advances, BMs still impact on survival and quality of life and the development of more effective systemic therapies represents an unmet clinical need.
A thorough analysis of the published literature including ongoing clinical trials has been performed, investigating concepts spanning from the pathophysiology of tumor microenvironment to clinical considerations with the aim to summarize the current and future locoregional and systemic strategies.
Different trials have investigated monotherapies and combination treatments, highlighting how the blood-brain barrier (BBB) represents a major problem hindering diffusion and consequently efficacy of such options. Trastuzumab has long been the mainstay of systemic therapy and over the last two decades other HER2-targeted agents including lapatinib, pertuzumab, and trastuzumab emtansine, as well as more recently neratinib, tucatinib, and trastuzumab deruxtecan, have been introduced in clinical practice after showing promising results in randomized controlled trials.
We ultimately propose an evidence-based treatment algorithm for clinicians treating HER2 + BCs patients with BMs.
约30%-50%的IV期HER2阳性乳腺癌（BC）会出现脑转移（BMs）。其治疗基于局部治疗和全身治疗。尽管治疗取得了进展，但脑转移仍会影响生存和生活质量，开发更有效的全身治疗方法仍是未满足的临床需求。
对已发表的文献进行了全面分析，包括正在进行的临床试验，研究了从肿瘤微环境的病理生理学到临床考量等概念，旨在总结当前和未来的局部区域及全身治疗策略。
不同试验研究了单一疗法和联合治疗，突出了血脑屏障（BBB）是阻碍此类药物扩散从而影响疗效的主要问题。长期以来，曲妥珠单抗一直是全身治疗的主要药物，在过去二十年中，其他HER2靶向药物，包括拉帕替尼、帕妥珠单抗和曲妥珠单抗 emtansine，以及最近的奈拉替尼、图卡替尼和曲妥珠单抗 deruxtecan，在随机对照试验中显示出有前景的结果后已被引入临床实践。
我们最终为治疗HER2 + BCs合并BMs患者的临床医生提出了一种基于证据的治疗算法。
