The association between Akt activation and resistance to hormone therapy in metastatic breast cancer
The association between Akt activation and resistance to hormone therapy in metastatic breast cancer
复制标题
DOI：
10.1016/j.ejca.2005.11.025
复制
发表时间：
2006-03-01
影响因子：
8.4
通讯作者：
Maehara, Y
中科院分区：
文献类型：
--
作者：
Tokunaga, E;Kataoka, A;Maehara, Y
在这项回顾性研究中，Akt激活和转移性乳腺癌的内分泌治疗的疗效之间的关系进行了调查。36例转移性乳腺癌患者接受内分泌治疗，通过免疫组化评估磷酸化Akt在Ser 473（pAkt）的表达来评估Akt的活化。还研究了内分泌治疗的功效与Akt活化、HER2状态和激素受体表达之间的关系。pAkt阳性表达12例（33.4%）。pAkt阳性患者内分泌治疗的疗效明显低于pAkt阴性患者（P < 0.01）。pAkt阳性也与较差的客观反应相关（P < 0.05）。HER2阳性组的临床获益率低于HER2阴性组（P < 0.05）。此外，HER2和pAkt阳性患者的临床获益最小（P < 0.01）。内分泌药物方面，芳香化酶抑制剂或促黄体生成素释放激素激动剂联合雌激素剥夺治疗的临床获益在pAkt阳性患者中显著低于pAkt阴性患者（P < 0.05）。此外，在pAkt阳性患者中，选择性雌激素受体调节剂的临床获益倾向于较小（P = 0.09）。因此，这些研究结果表明，Akt激活诱导转移性乳腺癌的内分泌耐药，而不管给予的内分泌药物的种类。我们的研究结果提示，HER2下游通路中Akt的激活在乳腺癌对内分泌治疗的抵抗中起重要作用。虽然我们的研究范围小，设计具有回顾性，但我们的研究结果表明，pAkt可能是乳腺癌内分泌治疗耐药的有用预测因子，同时也表明Akt的抑制可能会增加内分泌治疗的疗效。(c)2005 Elsevier Ltd.保留所有权利。
In this retrospective study, the relationship between Akt activation and the efficacy of endocrine therapy for metastatic breast cancer was investigated. Thirty-six metastatic breast cancer patients, treated with endocrine therapy, were evaluated for the activation of Akt by an immunohistochemical assessment of the expression of phosphorylated Akt at Ser 473 (pAkt). The relationship between the efficacy of endocrine therapy and Akt activation, HER2 status and hormone receptor expression was also investigated. of these 36 cases, 12 cases (33.4%) were considered to show a positive pAkt expression. In the pAkt-positive patients, endocrine therapy demonstrated a worse efficacy than in pAkt-negative patients (P < 0.01). pAkt positivity was also associated with a poorer objective response (P < 0.05). The clinical benefit rate was lower in HER2 positive groups than in HER2 negative group (P < 0.05). In addition, the clinical benefit was the smallest in both the HER2 and pAkt-positive patients (P < 0.01). Regarding the endocrine agents, the clinical benefit of estrogen deprivation therapy with aromatase inhibitor or luteinising hormone-releasing hormone agosists was significantly lower in the pAkt-positive patients than that in the pAkt-negative ones (P < 0.05). in addition, there was a tendency for clinical benefit of selective estrogen receptor modulator to be smaller in the pAkt-positive patients (P = 0.09). These findings, therefore, suggest that Akt activation induces endocrine resistance in metastatic breast cancer, irrespective of the kind of endocrine agents that were administered. our findings suggest that the activation of Akt in the downstream pathway of HER2 plays an important role in the resistance to endocrine therapy for breast cancer. Although our study was small in scope and retrospective in design, our findings suggest that pAkt may be a useful predictor of resistance to endocrine therapy for breast cancer, while also suggesting that the inhibition of Akt may increase the efficacy of endocrine therapy. (c) 2005 Elsevier Ltd. All rights reserved.