The predictive role of phosphatase and tensin homolog (PTEN) loss, phosphoinositol-3 (PI3) kinase (PIK3CA) mutation, and PI3K pathway activation in sensitivity to trastuzumab in HER2-positive breast cancer: a meta-analysis
The predictive role of phosphatase and tensin homolog (PTEN) loss, phosphoinositol-3 (PI3) kinase (PIK3CA) mutation, and PI3K pathway activation in sensitivity to trastuzumab in HER2-positive breast cancer: a meta-analysis
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DOI：
10.1185/03007995.2013.794775
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发表时间：
2013-06-01
影响因子：
2.3
通讯作者：
Lu, Jinsong
中科院分区：
文献类型：
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作者：
Wang, Yaohui;Liu, Yu;Lu, Jinsong
目的：在体外研究中，磷酸肌醇-3(PI3)激酶(PIK3CA)的磷酸酶和张力蛋白同源酶(PTEN)缺失或激活突变可能与曲妥珠单抗耐药有关，但在临床研究中这一问题存在争议。因此，我们进行了一项Meta分析，以评估PTEN缺失、PIK3CA突变与HER2阳性乳腺癌患者曲妥珠单抗治疗效果的关系。方法：通过计算机检索PubMed数据库、美国临床肿瘤学会年会、圣安东尼奥乳腺癌研讨会和国际圣加伦乳腺癌会议的在线论文集。结果：在HER2阳性的局部晚期乳腺癌患者中，PTEN缺失、PIK3CA突变和PI3K激活与曲妥珠单抗新辅助治疗的有效率无关(PTEN缺失：RR=0.687，95%CI：0.439~1.074，P=0.099；PIK3CA突变：RR=1.114，95%CI：0.453~2.735，P=0.814；PI3K激活：RR=0.787，95%CI：0.417~1.484，P=0.459；RR=0.772，95%CI：0.387~1.539，P=0.462)。在HER2阳性的早期乳腺癌患者中，抑癌基因缺失与曲妥珠单抗辅助治疗的无病生存率无关(HR=1.096，95%CI：0.706~1.700，P=0.684)。在HER2阳性的复发或转移性乳腺癌患者中，PTEN的缺失与曲妥珠单抗抢救治疗的疗效差显著相关(RR=0.682，95%CI：0.550~0.846，P=0.000)。结论：在HER2阳性的复发或转移性乳腺癌患者中，PTEN的缺失可能预示着对曲妥珠单抗抢救治疗的抵抗。由于样本量小，化疗方案中的异质性很大，需要进一步的研究来阐明PTEN缺失、PIK3CA突变和曲妥珠单抗在新辅助和辅助治疗环境中的疗效之间的关系。
Objective:Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be related to trastuzumab resistance in in vitro studies; however, this issue in clinical studies is controversial. Therefore, we conducted a meta-analysis to assess the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in HER2-positive breast cancer patients.Methods:A computerized search was performed through the PubMed database, the online proceedings of the American Society of Clinical Oncology Annual Meetings, the San Antonio Breast Cancer Symposium and the International St. Gallen Breast Cancer Conference. Ten eligible studies including 1889 cases were identified.Results:In HER2-positive locally advanced breast cancer patients, neither PTEN loss, PIK3CA mutation nor PI3K activation was associated with the response rate of trastuzumab-based neoadjuvant treatment (PTEN loss: RR = 0.687, 95% CI: 0.439-1.074, P = 0.099; PIK3CA mutation: RR = 1.114, 95% CI: 0.453-2.735, P = 0.814; PI3K activation: RR = 0.787, 95% CI: 0.417-1.484, P = 0.459; RR = 0.772, 95% CI: 0.387-1.539, P = 0.462). In HER2-positive early stage breast cancer patients, PTEN loss was not associated with the disease-free survival (DFS) rate of trastuzumab-based adjuvant treatment (HR = 1.096, 95% CI: 0.706-1.700, P = 0.684). In HER2-positive recurrent or metastatic breast cancer patients, PTEN loss was significantly correlated with poorer efficacy of trastuzumab-based salvage treatment (RR = 0.682, 95% CI: 0.550-0.846, P = 0.000).Conclusions:In HER2-positive recurrent or metastatic breast cancer patients PTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.