Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab.
Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab.
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DOI：
10.1038/bjc.2013.164
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发表时间：
2013-05-14
影响因子：
8.8
通讯作者：
Bieche I
中科院分区：
文献类型：
--
作者：
Cizkova M;Dujaric ME;Lehmann-Che J;Scott V;Tembo O;Asselain B;Pierga JY;Marty M;de Cremoux P;Spyratos F;Bieche I
磷脂酰肌醇3-激酶（PI 3 K）通路激活已被认为会对乳腺癌患者的抗HER 2治疗反应产生负面影响。本研究的重点是PIK 3CA基因的突变，该基因编码两个PI 3 K亚基之一。在80例接受1年曲妥珠单抗治疗的HER 2阳性患者中，通过直接测序评估PIK 3CA突变。所有患者术前均接受4个周期的蒽环类药物化疗，随后接受4个周期的多西他赛和1年的曲妥珠单抗治疗，从术前第一个周期的多西他赛开始，并在术后继续（新辅助曲妥珠单抗组，n=43），或仅在术后（辅助曲妥珠单抗组，n=37）。PIK 3CA突变在17个肿瘤中发现（21.3%）。与突变肿瘤患者相比，PIK 3CA野生型患者的无病生存期（DFS）更好（P=0.0063）。通过组合PIK 3CA状态和治疗组，确定了具有显著不同DFS（P=0.0013）的四个独立预后组。这些结果证实，与野生型肿瘤患者相比，PIK 3CA突变患者接受曲妥珠单抗治疗的HER 2阳性患者的结局显著更差。
Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients. The present study focused on mutations of the PIK3CA gene, encoding one of the two PI3K subunits. PIK3CA mutations were assessed by direct sequencing in 80 HER2-positive patients treated with 1 year of trastuzumab. All patients preoperatively received four cycles of anthracycline-based chemotherapy, followed by four cycles of docetaxel and 1 year of trastuzumab, starting either before surgery with the first cycle of docetaxel and continuing after surgery (neoadjuvant trastuzumab arm, n=43), or only after surgery (adjuvant trastuzumab arm, n=37). PIK3CA mutations were found in 17 tumours (21.3%). Better disease-free survival (DFS) was observed in patients with PIK3CA wild-type compared with mutated tumours (P=0.0063). By combining PIK3CA status and treatment arms, four separate prognostic groups with significantly different DFS (P=0.0013) were identified. These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA-mutated compared with wild-type tumours.
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影响因子：
8
作者：
Zhao, L.;Vogt, P. K.
通讯作者：
Vogt, P. K.
影响因子：
45.3
作者：
Dave, Bhuvanesh;Migliaccio, Ilenia;Chang, Jenny C.
通讯作者：
Chang, Jenny C.
影响因子：
3.8
作者：
Wang L;Zhang Q;Zhang J;Sun S;Guo H;Jia Z;Wang B;Shao Z;Wang Z;Hu X
通讯作者：
Hu X
磷脂酰肌醇3-激酶过度激活导致拉帕替尼的抗性，这是由mTOR/磷脂酰/磷脂酰肌醇3-激酶抑制剂NVP-BEZ235逆转的。
影响因子：
11.2
作者：
Eichhorn PJ;Gili M;Scaltriti M;Serra V;Guzman M;Nijkamp W;Beijersbergen RL;Valero V;Seoane J;Bernards R;Baselga J
通讯作者：
Baselga J
影响因子：
11.2
作者：
Stemke-Hale K;Gonzalez-Angulo AM;Lluch A;Neve RM;Kuo WL;Davies M;Carey M;Hu Z;Guan Y;Sahin A;Symmans WF;Pusztai L;Nolden LK;Horlings H;Berns K;Hung MC;van de Vijver MJ;Valero V;Gray JW;Bernards R;Mills GB;Hennessy BT
通讯作者：
Hennessy BT