Tanei Tomonori, Seno Shigeto, Sota Yoshiaki, Hatano Takaaki, Kitahara Yuri, Abe Kaori, Masunaga Nanae, Tsukabe Masami, Yoshinami Tetsuhiro, Miyake Tomohiro, Shimoda Masafumi, Matsuda Hideo, Shimazu Kenzo
Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, 2-2-E10 Yamadaoka, Suita 565-0871, Osaka, Japan.
Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita 565-0871, Osaka, Japan.
Cancers (Basel). 2024 Mar 5;16(5):1062. doi: 10.3390/cancers16051062.
Breast cancer tumors frequently have intratumoral heterogeneity (ITH). Tumors with high ITH cause therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to a poor prognosis for HER2-targeted adjuvant therapy resistance in primary breast cancers.
This study included patients with primary breast cancer ( = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with the HER2 gene copy number within a tumor sample. Each tumor was classified into a biphasic grade graph (high heterogeneity [HH]) group or a monophasic grade graph (low heterogeneity [LH]) group based on heterogeneity. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up.
Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: < 0.001 (HH:63% vs. LH:91% at 10 years) and for the OS: = 0.012 (HH:78% vs. LH:95% at 10 years).
High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach to heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.
乳腺癌肿瘤常具有瘤内异质性（ITH）。具有高ITH的肿瘤会导致治疗耐药，并且在针对人表皮生长因子受体2（HER2）的治疗反应中存在HER2异质性。本研究旨在调查高HER2异质性水平是否与原发性乳腺癌中HER2靶向辅助治疗耐药的不良预后在临床上相关。
本研究纳入了接受HER2靶向辅助治疗的原发性乳腺癌患者（n = 251）。HER2异质性通过肿瘤样本中HER2基因拷贝数的HER2荧光原位杂交扩增（FISH）分布直方图的形状来体现。根据异质性，将每个肿瘤分为双相分级图（高异质性[HH]）组或单相分级图（低异质性[LH]）组。对两组进行了为期十年的年度随访，评估无病生存期（DFS）和总生存期（OS）。
在251例HER2阳性乳腺癌患者中，分别有46例（18.3%）和205例（81.7%）被分类为HH组和LH组。HH组比LH组有更多远处转移且预后更差（DFS：P < 0.001（10年时HH组为63% vs. LH组为91%），OS：P = 0.012（10年时HH组为78% vs. LH组为95%）。
高HER2异质性是HER2阳性乳腺癌患者的不良预后因素。一种由HER2 FISH分布形状体现的异质性新方法，可能在HER2辅助治疗后患者的预后预测中具有临床实用性。
Zotero 插件