Nishimura Reiki, Toh Uhi, Tanaka Maki, Saimura Michiyo, Okumura Yasuhiro, Saito Tsuyoshi, Tanaka Toshihiro, Teraoka Megumi, Shimada Kazuo, Katayama Kazuhisa, Koga Toshihiro, Kurashita Kaname, Hasegawa Satoshi, Todoroki Hidekazu, Kai Yuichiro, Ohi Yasuyo, Toyoshima Satoshi, Arima Nobuyuki, Mitsuyama Shoshu, Tamura Kazuo
Department of Breast Oncology, Kumamoto Shinto General Hospital, Kumamoto, Japan.
Oncology. 2017;93(1):51-61. doi: 10.1159/000468521. Epub 2017 May 6.
The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer.
Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing.
The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs.
LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.
本研究旨在探讨人表皮生长因子受体2（HER2）相关生物标志物与拉帕替尼联合卡培他滨（LC）治疗效果之间的相关性，并评估雌激素受体（ER）状态对曲妥珠单抗难治性HER2阳性晚期乳腺癌的影响。
80例患者纳入本研究。使用VeraTag检测法定量总HER2、p95HER2和总HER3表达。采用免疫组织化学评估PTEN（磷酸酶和张力蛋白同源物）和p95表达，采用直接测序评估PIK3CA突变。
LC的有效率为30%，临床获益率为51.3%，中位无进展生存期（PFS）为174.5天。ER阴性与较高的HER2和p95HER2显著相关。在无反应者中常观察到较低的HER2和PIK3CA突变。高p95HER2表达与较长的PFS相关，尤其是在HER2高表达和ER阳性的病例中。在同一亚组中，无PIK3CA突变的患者显示出更长的PFS。LC治疗后的总生存期与复发器官数量显著相关。
LC治疗对曲妥珠单抗难治性HER2阳性乳腺癌有效。此外，生物标志物表达因ER状态而异，高p95HER2表达和野生型PIK3CA基因与较长的PFS相关，尤其是在ER阳性病例中。
