Gong Chengcheng, Liu Cheng, Tao Zhonghua, Zhang Jian, Wang Leiping, Cao Jun, Zhao Yannan, Xie Yizhao, Hu Xichun, Yang Zhongyi, Wang Biyun
Department of Breast and Urological Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cancers (Basel). 2022 Aug 17;14(16):3973. doi: 10.3390/cancers14163973.
Background: This study aimed to evaluate tumor heterogeneity of metastatic breast cancer (MBC) and investigate its impact on the efficacy of pyrotinib in patients with HER2-positive MBC. Methods: MBC patients who underwent 18F-FDG PET/CT before pyrotinib treatment were included. Temporal and spatial tumor heterogeneity was evaluated by the discordance between primary and metastatic immunohistochemistry (IHC) results and baseline 18F-FDG uptake heterogeneity (intertumoral and intratumoral heterogeneity indexes: HI-inter and HI-intra), respectively. Progression-free survival (PFS) was estimated by the Kaplan−Meier method and compared by a log-rank test. Results: A total of 572 patients were screened and 51 patients were included. In 36 patients with matched IHC results, 25% of them had HER2 status conversion. Patients with homogenous HER2 positivity had the longest PFS, followed by patients with gained HER2 positivity, while patients with HER2 negative conversion could not benefit from pyrotinib (16.8 vs. 13.7 vs. 3.6 months, p < 0.0001). In terms of spatial heterogeneity, patients with high HI-intra and HI-inter had significantly worse PFS compared to those with low heterogeneity (10.6 vs. 25.3 months, p = 0.023; 11.2 vs. 25.3 months, p = 0.040). Conclusions: Temporal heterogeneity of HER2 status and spatial heterogeneity of 18F-FDG uptake could predict the treatment outcome of pyrotinib in patients with HER2-positive MBC, which provide practically applicable methods to assess tumor heterogeneity and guidance for treatment decisions.
本研究旨在评估转移性乳腺癌（MBC）的肿瘤异质性，并探讨其对HER2阳性MBC患者吡咯替尼疗效的影响。方法：纳入在吡咯替尼治疗前接受18F-FDG PET/CT检查的MBC患者。分别通过原发灶和转移灶免疫组化（IHC）结果的不一致性以及基线18F-FDG摄取异质性（瘤间和瘤内异质性指数：HI-inter和HI-intra）评估时间和空间肿瘤异质性。采用Kaplan-Meier法估计无进展生存期（PFS），并通过对数秩检验进行比较。结果：共筛选572例患者，纳入51例。在36例IHC结果匹配的患者中，25%发生了HER2状态转换。HER2均为阳性的患者PFS最长，其次是获得性HER2阳性的患者，而发生HER2阴性转换的患者无法从吡咯替尼中获益（16.8个月 vs. 13.7个月 vs. 3.6个月，p<0.0001）。在空间异质性方面，HI-intra和HI-inter高的患者与低异质性患者相比，PFS显著更差（10.6个月 vs. 25.3个月，p = 0.023；11.2个月 vs. 25.3个月，p = 0.040）。结论：HER2状态的时间异质性和18F-FDG摄取的空间异质性可预测HER2阳性MBC患者吡咯替尼的治疗结局，为评估肿瘤异质性提供了切实可行的方法，并为治疗决策提供了指导。
