成纤维细胞生长因子受体 4（FGFR4）Arg388 基因型与原发性乳腺癌新辅助化疗的病理完全缓解相关。
FGFR4 Arg388 genotype is associated with pathological complete response to neoadjuvant chemotherapy for primary breast cancer.
机构信息
Department of Obstetrics and Gynecology, University Hospital Heidelberg; Department of Molecular Genetics.
Department of Biostatistics.
出版信息
Ann Oncol. 2010 Aug;21(8):1636-1642. doi: 10.1093/annonc/mdq017. Epub 2010 Feb 10.
BACKGROUND
A single-nucleotide polymorphism (SNP) in the FGFR4 gene is associated with poor prognosis in solid tumors. A recent study presented the first evidence that FGFR4 Arg388 could predict resistance to adjuvant chemotherapy in breast cancer. The present study evaluates the potential of this SNP to predict response to neoadjuvant chemotherapy (NCT) for primary breast cancer (PBC).
METHODS
As part of a randomized phase II trial, 257 patients received either doxorubicin-cyclophosphamide (AC) or doxorubicin-pemetrexed (AP) followed by docetaxel (Doc; Taxotere) as NCT for T2-4/N0-2/M0 PBC. FGFR4 genotype analyzed on germline DNA was correlated with clinicopathologic variables, clinical response, and pathological complete response (pCR) using univariate and multivariate analyses.
RESULTS
Only axillary lymph node status was associated with FGFR4 Arg388 [odds ratio (OR) 1.82, P = 0.03]. Joint analysis of both treatment arms revealed a correlation of FGFR4 Arg388 with clinical response (OR 2.14, P = 0.03) but not with pCR. In the AC-Doc arm, however, FGFR4 Arg388 was a strong predictor of pCR in the multivariate analysis (OR 3.79, P = 0.03). A significant interaction between FGFR4 genotype and treatment (P = 0.01) was found, indicating a therapy-specific effect.
CONCLUSION
We provide the evidence that FGFR4 388Arg is an independent predictor of pCR following AC-Doc as NCT in PBC.
背景
成纤维细胞生长因子受体 4（FGFR4）基因中的单核苷酸多态性（SNP）与实体瘤的不良预后相关。最近的一项研究首次表明，FGFR4 Arg388 可预测乳腺癌辅助化疗的耐药性。本研究评估了该 SNP 预测原发性乳腺癌（PBC）新辅助化疗（NCT）反应的潜力。
方法
作为一项随机 II 期试验的一部分，257 例患者接受阿霉素环磷酰胺（AC）或阿霉素培美曲塞（AP）联合多西他赛（Doc；Taxotere）作为 T2-4/N0-2/M0 PBC 的 NCT。对来源于胚系 DNA 的 FGFR4 基因型进行分析，并使用单变量和多变量分析，将其与临床病理变量、临床反应和病理完全缓解（pCR）相关联。
结果
仅腋窝淋巴结状态与 FGFR4 Arg388 相关（优势比[OR]1.82，P=0.03）。对两个治疗组的联合分析显示，FGFR4 Arg388 与临床反应相关（OR 2.14，P=0.03），但与 pCR 无关。然而，在 AC-Doc 组中，FGFR4 Arg388 在多变量分析中是 pCR 的一个强有力的预测因子（OR 3.79，P=0.03）。发现 FGFR4 基因型与治疗之间存在显著的相互作用（P=0.01），表明存在治疗特异性效应。
结论
我们提供的证据表明，FGFR4 388Arg 是 PBC 中接受 AC-Doc 作为 NCT 后 pCR 的独立预测因子。
Zotero 插件