Centre for Cancer Therapeutics, Ottawa Hospital Research Institute; The Division of Gynaecologic Oncology, The Ottawa Hospital, Ottawa.
The NCIC Clinical Trials Group, Kingston.
Ann Oncol. 2011 Nov;22(11):2403-2410. doi: 10.1093/annonc/mdq770. Epub 2011 Mar 2.
Breast cancer 1 (BRCA1) protein inactivation in sporadic ovarian carcinoma (OC) is common and low BRCA1 expression is linked with platinum sensitivity. The clinical validation of BRCA1 as a prognostic marker in OC remains unresolved.
In 251 patient samples from the NCIC CTG clinical trial, OV.16, BRCA1 protein expression was determined by immunohistochemistry.
For all patients, when BRCA1 score was analyzed as a continuous variable, there was no significant correlation between BRCA1 protein expression and progression-free survival (PFS) [adjusted hazard ratio (HR) = 1.15 (0.96-1.37), P = 0.12] or response rate [HR = 0.89 (0.70-1.12), P = 0.32]. In the 116 patients with minimal residual disease (RD), higher BRCA1 expression correlated significantly with worse PFS [HR = 1.40 (1.04-1.89), P = 0.03]. Subgroup analysis divided patients with minimal RD into low (BRCA1 ≤2.5) and high (BRCA1 >2.5) expression groups. Patients with low BRCA1 expression had a more favorable outcome [median PFS was 24.7 and 16.6 months in patients with low and high BRCA1, respectively; HR = 0.56 (0.35-0.89), P = 0.01].
This study suggests that BRCA1 protein is a prognostic marker in sporadic OC patients with minimal RD. Further research is needed to evaluate BRCA1 as a predictive biomarker and to target BRCA1 expression to enhance chemotherapeutic sensitivity.
散发性卵巢癌（OC）中乳腺癌 1 号（BRCA1）蛋白失活很常见，低 BRCA1 表达与铂类敏感性相关。BRCA1 是否可作为 OC 的预后标志物仍有待临床验证。
在 NCIC CTG 临床试验 OV.16 的 251 例患者样本中，采用免疫组化法测定 BRCA1 蛋白表达。
在所有患者中，当 BRCA1 评分作为连续变量进行分析时，BRCA1 蛋白表达与无进展生存期（PFS）[调整后的危险比（HR）=1.15（0.96-1.37），P=0.12]或反应率[HR=0.89（0.70-1.12），P=0.32]均无显著相关性。在 116 例有微小残留病灶（RD）的患者中，BRCA1 高表达与更差的 PFS 显著相关[HR=1.40（1.04-1.89），P=0.03]。亚组分析将微小 RD 患者分为低 BRCA1 表达（BRCA1≤2.5）和高 BRCA1 表达（BRCA1＞2.5）两组。低 BRCA1 表达的患者预后较好[低 BRCA1 表达患者的中位 PFS 分别为 24.7 个月和 16.6 个月；HR=0.56（0.35-0.89），P=0.01]。
本研究表明 BRCA1 蛋白是微小 RD 散发性 OC 患者的预后标志物。还需要进一步的研究来评估 BRCA1 是否可作为预测性生物标志物，并靶向 BRCA1 表达以增强化疗敏感性。
