卵巢癌患者中 BRCA1 和 BRCA2 种系突变的频率及其对治疗结果的影响。,Cancer Management and Research

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卵巢癌患者中 BRCA1 和 BRCA2 种系突变的频率及其对治疗结果的影响。
Cancer Management and Research ( IF 2.5 ) Pub Date : 2019-07-08 , DOI: 10.2147/cmar.s206817
Mohamed Ashour _{1,

2} , Hanan Ezzat Shafik ₃

Affiliation

工作目的报告卵巢癌患者 BRCA1/2 突变的发生率和变异，探索其对治疗结果的影响。患者和方法总共有 104 名上皮性卵巢癌患者被前瞻性地招募到该研究中。分析包括对 BRCA1/2 基因的所有翻译外显子和紧邻的内含子区域进行测序。评估了对多线化疗的反应，以及 BRCA 基因突变对无进展生存期 (PFS) 和总生存期 (OS) 的影响。结果在21.15%的患者中发现了致病性BRCA1/2突变。BRCA1 突变占总突变的 68.2%。确定了两个新的 BRCA1 突变。诊断时的年龄是致病性 BRCA1/2 突变存在的一个强有力的预测因素。有癌症家族史的患者 BRCA 突变发生率较高（P=0.005）。高达 72% 的 BRCA 突变患者被诊断为晚期。高级别浆液性肿瘤的致病突变发生率较高（P=0.07）。对新辅助化疗的反应很高（93.9%）。所有患者均接受了手术，其中 73.1% 的患者最佳。高达85.6%的患者接受了辅助化疗。复发率为45.2%。BRCA 携带者内脏转移更常见（P=0.01）。携带致病性 BRCA1/2 突变的患者的中位 PFS 较长，为 42.43 个月（95% CI 32.04-52.83），而非携带者为 22.24 个月（95% CI 14.83-29.58）（P=0.08）。BRCA 突变患者的 OS 为 64.32 个月 (95% CI 38.09-90.06)，而非携带者为 56.63 个月 (95% CI 50.05-63.21) (P=0.04)。在多变量分析中，早期诊断和最佳减瘤是更好的 PFS 和 OS 的唯一独立预测因素。结论我们记录了该患者队列中的许多致病性 BRCA1 和 2 个突变。检测到两个新的突变。BRCA 状态似乎会影响卵巢癌患者的生存率。

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Frequency of germline mutations in BRCA1 and BRCA2 in ovarian cancer patients and their effect on treatment outcome.

AIM OF WORK Reporting the incidence and the variants of BRCA1/2 mutations in ovarian cancer patients exploring their effects on the treatment outcomes. PATIENTS AND METHODS In total, 104 patients with epithelial ovarian cancer were prospectively recruited to the study. Analysis consisted of the sequencing of all the translated exons and immediately adjacent intronic regions of the BRCA1/2 genes. Responses to multiple lines of chemotherapy were assessed, as well as the effect of BRCA gene mutations on progression-free survival (PFS) and overall survival (OS). RESULTS Pathogenic BRCA1/2 mutations were found in 21.15% of the patients. BRCA1 mutations represented 68.2% of the total mutations. Two novel BRCA1 mutations were identified. Age at diagnosis was a strong predictor of the presence of a pathogenic BRCA1/2 mutation. Patients with a family history of cancer had a higher incidence of BRCA mutations (P=0.005). As high as 72% of the patients with BRCA mutations were diagnosed at advanced stage. High-grade serous tumors have a higher incidence of pathogenic mutation (P=0.07). Response to neoadjuvant chemotherapy was high (93.9%). All patients underwent surgery which was optimal in 73.1% of the patients. As high as 85.6% of the patients received adjuvant chemotherapy. Relapse rate was 45.2%. Visceral metastasis was more often in BRCA carriers (P=0.01). Patients carrying pathogenic BRCA1/2 mutations had a longer median PFS of 42.43 months (95% CI 32.04-52.83) compared to 22.24 months (95% CI 14.83-29.58) for non-carriers (P=0.08). OS was 64.32 months (95% CI 38.09-90.06) for BRCA mutation patients versus 56.63 months (95% CI 50.05-63.21) (P=0.04) for non-carriers. In multivariate analysis, early stage at diagnosis and optimal debulking were the only independent predictors of better PFS and OS. CONCLUSION We documented a number of pathogenic BRCA1 and 2 mutations in this patients cohort; two novel mutations were detected. BRCA status seemed to affect survival in ovarian cancer patients.

更新日期：2019-11-01

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