p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane,British Journal of Cancer

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p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane
British Journal of Cancer ( IF 6.4 ) Pub Date : 2024-01-05 , DOI: 10.1038/s41416-023-02549-8
Hélène Vanacker ₁ , Isabelle Treilleux ₁ , Camille Schiffler ₁ , Ivan Bieche ₂ , Mario Campone ₃ , Anne Patsouris ₃ , Monica Arnedos ₄ , Paul H Cottu ₂ , Jean-Philippe Jacquin ₅ , Florence Dalenc ₆ , Antoine Pinton ₂ , Nicolas Servant ₂ , Valéry Attignon ₁ , Etienne Rouleau ₄ , Alain Morel _{3,

7} , François Legrand ₈ , Marta Jimenez ₈ , Fabrice Andre ₄ , Thomas Bachelot ₁

Affiliation

Background

To identify patients most likely to respond to everolimus, a mammalian target of rapamycin (mTOR) inhibitor, a prospective biomarker study was conducted in hormone receptor-positive endocrine-resistant metastatic breast cancer patients treated with exemestane-everolimus therapy.

Methods

Metastatic tumor biopsies were processed for immunohistochemical staining (p4EBP1, PTEN, pAKT, LKB1, and pS6K). ESR1, PIK3CA and AKT1 gene mutations were detected by NGS. The primary endpoint was the association between the p4EBP1 expression and clinical benefit rate (CBR) at 6 months of everolimus plus exemestane treatment.

Results

Of 150 patients included, 107 were evaluable for the primary endpoint. p4EBP1 staining above the median (Allred score ≥6) was associated with a higher CBR at 6 months (62% versus 40% in high-p4EBP1 versus low-p4EBP1, χ2 test, p = 0.026) and a longer progression-free survival (PFS) (median PFS of 9.2 versus 5.8 months in high-p4EBP1 versus low-p4EBP1; p = 0.02). When tested with other biomarkers, only p4EBP1 remained a significant predictive marker of PFS in multivariate analysis (hazard ratio, 0.591; p = 0.01).

Conclusions

This study identified a subset of patients with hormone receptor-positive endocrine-resistant metastatic breast cancer and poor outcome who would derive less benefit from everolimus and exemestane. p4EBP1 may be a useful predictive biomarker in routine clinical practice.

Clinical Trial Registration

NCT02444390.

中文翻译：

p4EBP1 染色可预测接受依维莫司和依西美坦治疗的 ER 阳性内分泌耐药转移性乳腺癌患者的结局

背景

为了确定最有可能对依维莫司（雷帕霉素的一种哺乳动物靶标（mTOR）抑制剂）有反应的患者，在接受依西美坦-依维莫司治疗治疗的激素受体阳性内分泌耐药转移性乳腺癌患者中进行了一项前瞻性生物标志物研究。

方法

转移性肿瘤活检进行免疫组织化学染色（p4EBP1 、 PTEN 、 pAKT 、 LKB1 和 pS6K）。NGS 检测 ESR1 、 PIK3CA 和 AKT1 基因突变。主要终点是依维莫司加依西美坦治疗 6 个月时 p4EBP1 表达与临床获益率（CBR）之间的关联。

结果

在纳入的 150 例患者中，107 例可评估主要终点。高于中位数的 p4EBP1 染色（Allred 评分 ≥6）与 6 个月时的较高 CBR 相关（高 p4EBP1 与低 p4EBP1 相比 62% 对 40%，χ2 检验，p = 0.026）和更长的无进展生存期（PFS）（高 p4EBP1 与低 p4EBP1 的中位 PFS 为 9.2 对 5.8 个月;p = 0.02）。当与其他生物标志物一起测试时，在多变量分析中，只有 p4EBP1 仍然是 PFS 的重要预测标志物（风险比，0.591;p = 0.01）。