Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer
Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer
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DOI：
10.1007/s10549-014-3080-x
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发表时间：
2014-08-01
影响因子：
3.8
通讯作者：
Dixon, J. M.
中科院分区：
文献类型：
--
作者：
Arthur, L. M.;Turnbull, A. K.;Dixon, J. M.
磷脂酰肌醇-3-激酶途径在乳腺癌的增殖、迁移和存活中发挥重要作用，并且可能在内分泌治疗耐药中发挥作用。 PIK3CA 突变或功能性 PTEN 缺失会导致通路激活。使用基于 qPCR 的突变检测对 120 名接受内分泌治疗的乳腺癌患者的匹配原发性和复发性样本进行了分析，涵盖 PIK3CA 中的 8 个突变热点。通过免疫组织化学分析 PTEN。样本在复发的解剖位置方面得到了很好的表征（转移性淋巴结或局部复发，而不是对侧或同侧新的原发性癌症）。总共有 43% 的患者在诊断时至少有一种 PIK3CA 突变，41% 在复发时有突变。在主要内分泌治疗后局部复发、转移或进展的患者中，只有 8% 的患者改变了 PIK3CA 突变状态（4 例增加，2 例丢失，总共 76 例）。 PIK3CA 突变状态最常见的变化见于治疗侧乳房或对侧乳房出现新癌症的患者（64%，3 次增加，4 次减少，总共 11 次）。大多数乳腺癌患者的 PIK3CA 突变状态不会改变，并且 PIK3CA 突变的获得并不导致内分泌抵抗的发生。与保留 PTEN 的肿瘤相比，诊断时 PTEN 缺失与进展时间显着缩短相关。这些是目前可获得的与 PIK3CA 状态、复发部位和内分泌抵抗相关的最全面的数据。
The phosphatidylinositol-3-kinase pathway plays an important role in proliferation, migration and survival in breast cancer and may play a role in resistance to endocrine therapy. Pathway activation occurs as a result of mutations in PIK3CA or loss of functional PTEN. Matched primary and recurrent samples from 120 breast cancer patients treated with endocrine therapy were profiled with a qPCR-based mutation assay covering eight mutational hotspots in PIK3CA. PTEN was assayed by immunohistochemistry. Samples were well characterized with respect to anatomic location of recurrence (metastatic nodal or local recurrence as opposed to contralateral or ipsilateral new primary cancers). In total, 43 % of patients had at least one PIK3CA mutation at diagnosis, and 41 % had a mutation at the time of recurrence. Only 8 % of patients with local recurrence, metastatic disease or progression on primary endocrine treatment changed their PIK3CA mutation status (four gains, two losses, total 76). The most common changes in PIK3CA mutation status were seen in patients who developed a new cancer either in the treated or contralateral breast (64 %, three gains, four losses, total 11). PIK3CA mutation status does not change in the majority of patients with breast cancer and the acquisition of mutations in PIK3CA is not responsible for the development of endocrine resistance. PTEN loss at diagnosis is associated with a significantly shorter time to progression compared with tumours in which PTEN was retained. These are the most comprehensive data currently available correlating PIK3CA status, site of recurrence and endocrine resistance.