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Folate receptor alpha expression associates with improved disease-free survival in triple negative breast cancer patients.
npj Breast Cancer ( IF 6.5 ) Pub Date : 2020-02-04 , DOI: 10.1038/s41523-020-0147-1
Nadine Norton 1 , Bahaaeldin Youssef 1 , David W Hillman 2 , Aziza Nassar 3 , Xochiquetzal J Geiger 3 , Brian M Necela 1 , Heshan Liu 2 , Kathryn J Ruddy 4 , Mei-Yin C Polley 2 , James N Ingle 4 , Fergus J Couch 2, 5 , Edith A Perez 6 , Minetta C Liu 4, 5 , Jodi M Carter 5 , Roberto A Leon-Ferre 4 , Judy C Boughey 7 , Elizabeth B Somers 8 , Krishna R Kalari 2 , Daniel W Visscher 5 , Matthew P Goetz 4, 9 , Keith L Knutson 10
Affiliation  

Triple negative breast cancer (TNBC) comprises 15-20% of all invasive breast cancer and is associated with a poor prognosis. As therapy options are limited for this subtype, there is a significant need to identify new targeted approaches for TNBC patient management. The expression of the folate receptor alpha (FRα) is significantly increased in patients with TNBC and is therefore a potential biomarker and therapeutic target. We optimized and validated a FRα immunohistochemistry method, specific to TNBC, to measure FRα expression in a centrally confirmed cohort of 384 patients with TNBC in order to determine if expression of the protein is associated with invasive disease-free survival (IDFS) and overall survival (OS). The FRα IHC demonstrated exceptional performance characteristics with low intra- and interassay variability as well as minimal lot-to-lot variation. FRα expression, which varied widely from sample to sample, was detected in 274 (71%) of the TNBC lesions. In a multivariable model adjusted for baseline characteristics, FRα expression was associated with improved IDFS (HR = 0.63, p = 0.01) but not with OS. The results demonstrate the potential of targeting the FRα in the majority of TNBC patients and suggest that variable expression may point to a need to stratify on FRα expression in clinical studies.

中文翻译:


叶酸受体α表达与三阴性乳腺癌患者无病生存率的改善相关。



三阴性乳腺癌 (TNBC) 占所有浸润性乳腺癌的 15-20%,且预后不良。由于该亚型的治疗选择有限,因此迫切需要为 TNBC 患者管理确定新的有针对性的方法。 TNBC 患者中叶酸受体 α (FRα) 的表达显着增加,因此是潜在的生物标志物和治疗靶点。我们优化并验证了针对 TNBC 的 FRα 免疫组织化学方法,以测量集中确诊的 384 名 TNBC 患者队列中的 FRα 表达,以确定该蛋白的表达是否与无侵袭性疾病生存 (IDFS) 和总生存相关(操作系统)。 FRα IHC 表现出卓越的性能特征,批内和批间变异性低,批次间变异极小。在 274 个 (71%) TNBC 病灶中检测到 FRα 表达,每个样本的表达差异很大。在根据基线特征进行调整的多变量模型中,FRα 表达与 IDFS 改善相关(HR = 0.63,p = 0.01),但与 OS 无关。结果证明了在大多数 TNBC 患者中靶向 FRα 的潜力,并表明可变表达可能表明需要在临床研究中对 FRα 表达进行分层。
更新日期:2020-02-04
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