Almost one-fifth of breast cancer cases express Human Epidermal Growth Factor-2 (HER2), and such expression is associated with highly proliferative tumors and poor prognosis. The introduction of anti-HER2 therapies has dramatically changed the natural course of this aggressive subtype of breast cancer. However, anti-HER2 therapy can be associated with substantial toxicities, mostly cardiac, and high cost. Over the past few years, there has been growing interest in de-escalation of anti-HER2 therapies to minimize adverse events and healthcare costs, while maintaining the efficacy of treatment. Data from clinical observations and single-arm studies have eluted to the minimal impact of anti-HER2 therapy in low-risk patients, like those with node-negative and small tumors. Though single-arm, the APT trial, in which patients with node-negative, small tumors received single-agent paclitaxel for 12 cycles plus trastuzumab for 1 year, was a practice-changing study. Several other recently published studies, like the PERSEPHONE trial, have shown more convincing data that 6 months of trastuzumab is not inferior to 12 months, in terms of disease-free survival (DFS), suggesting that de-escalating strategies with shorter treatment may be appropriate for some low-risk patients. Other de-escalating strategies involved an adaptive, response-directed approach, and personalized therapy that depends on tumor genomic profiling.
约五分之一的乳腺癌病例表达人类表皮生长因子受体2（HER2），这种表达与高增殖性肿瘤及不良预后相关。抗HER2疗法的引入显著改变了这一侵袭性乳腺癌亚型的自然病程。然而，抗HER2治疗可能伴随显著的毒性反应（主要为心脏毒性）及高昂费用。近年来，学界日益关注通过降阶梯抗HER2治疗来减少不良事件并降低医疗成本，同时维持治疗效果。临床观察和单臂研究数据显示，抗HER2治疗对低风险患者（如淋巴结阴性且肿瘤体积较小者）的疗效影响有限。尽管是单臂设计，APT试验（该试验中淋巴结阴性、肿瘤较小的患者接受12周期单药紫杉醇联合1年曲妥珠单抗治疗）仍成为改变临床实践的重要研究。其他近期发表的研究（如PERSEPHONE试验）提供了更具说服力的证据：在无病生存期（DFS）方面，6个月曲妥珠单抗治疗不劣于12个月疗程，提示缩短治疗时长的降阶梯策略可能适用于部分低风险患者。其他降阶梯策略还包括基于治疗反应的适应性调整方案，以及依赖肿瘤基因组谱分析的个体化治疗。
肿瘤(癌症)患者之家