Departments of Oncology.
Departments of Pathology, Clinical Sciences, Lund University.
Ann Oncol. 2010 Feb;21(2):238-244. doi: 10.1093/annonc/mdp293. Epub 2009 Jul 23.
Clinical trials implicate the estrogen receptor (ER) coactivator amplified in breast cancer 1 (AIB1) to be a prognostic and a treatment-predictive factor, although results are not unanimous. We have further investigated this using a controlled randomised trial of tamoxifen versus control.
A total of 564 premenopausal women were entered into a randomised study independent of ER status. Using a tissue microarray, AIB1 and ER were analysed by immunohistochemistry.
AIB1 scores were obtained from 349 women. High AIB1 correlated to factors of worse prognosis (human epidermal growth factor receptor 2, Nottingham histological grade 3, and lymph node metastases) and to ER negativity. In the control arm, high AIB1 was a negative prognostic factor for recurrence-free survival (RFS) (P = 0.02). However, ER-positive patients with high AIB1 responded significantly to tamoxifen treatment (P = 0.002), increasing RFS to the same level as for systemically untreated patients with low AIB1. Although ER-positive patients with low AIB1 had a better RFS from the beginning, this was not further improved by tamoxifen (P = 0.8).
In the control group, high AIB1 was a negative prognostic factor. However, ER-positive patients with high AIB1 responded significantly to tamoxifen. This implicates high AIB1 to be an independent predictive factor of improved response to tamoxifen and not, as has previously been discussed, a factor predicting tamoxifen resistance.
临床试验暗示乳腺癌 1 号受体(ER)共激活因子扩增物(AIB1)是一个预后和治疗预测因子,尽管结果并不一致。我们使用他莫昔芬与对照组的对照随机试验进一步对此进行了研究。
共有 564 名绝经前妇女进入了一项独立于 ER 状态的随机研究。使用组织微阵列,通过免疫组织化学分析 AIB1 和 ER。
从 349 名女性中获得了 AIB1 评分。高 AIB1 与预后不良的因素(人表皮生长因子受体 2、诺丁汉组织学 3 级和淋巴结转移)和 ER 阴性相关。在对照组中,高 AIB1 是无复发生存(RFS)的负预后因素(P = 0.02)。然而,ER 阳性且 AIB1 高的患者对他莫昔芬治疗有显著反应(P = 0.002),RFS 提高到与 AIB1 低的未接受系统治疗的患者相同水平。尽管 ER 阳性且 AIB1 低的患者从一开始就有更好的 RFS,但他莫昔芬并没有进一步改善(P = 0.8)。
在对照组中,高 AIB1 是一个负预后因素。然而,ER 阳性且 AIB1 高的患者对他莫昔芬有显著反应。这表明高 AIB1 是对他莫昔芬反应改善的独立预测因子,而不是如前所述的预测他莫昔芬耐药的因素。