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BRCA 基因突变的卵巢癌患者发生脑转移的风险增加。

Increased risk of brain metastases in ovarian cancer patients with BRCA mutations.

机构信息

Obstetrics, Gynecology, and Reproductive Sciences, Yale University, 800 Howard Avenue, New Haven, CT 06519, USA.

TESARO, Inc., 1000 Winter Street, Waltham, MA 02451, USA.

出版信息

Gynecol Oncol. 2019 Jun;153(3):568-573. doi: 10.1016/j.ygyno.2019.03.004. Epub 2019 Mar 12.

Abstract

PURPOSE

To estimate the risk for brain metastases in patients with ovarian cancer using real-world data, and assess whether BRCA mutations increase that risk.

METHODS

This retrospective study included 4515 patients diagnosed with ovarian cancer between January 1, 2011, and January 31, 2018, from the Flatiron Health database, a longitudinal, demographically, and geographically diverse database derived from electronic health records in the United States.

RESULTS

Forty-six (1%) patients were diagnosed with brain metastases after being diagnosed with ovarian cancer. Of 4515 patients with ovarian cancer, 10% had a known BRCA mutation, 37% had BRCA wildtype (BRCAwt), and the BRCA status of the remaining 51% was unknown/untested. Brain metastases were observed in 3% of patients with BRCA mutations compared with 0.6% of those with BRCAwt. The Kaplan-Meier estimate for the proportion of patients with brain metastases within 5 years of diagnosis was 5.7% in the population with BRCA mutations compared with 1.4% in those with BRCAwt (hazard ratio 4.44; 95% confidence interval, 1.97, 10.00; P < 0.0001). These data demonstrate that patients with a BRCA mutation had a significantly higher risk for brain metastases than those without.

CONCLUSION

Despite being a rare manifestation of ovarian cancer, the possibility of developing brain metastases should be considered in these patients, especially in patients with a BRCA mutation. The availability of new therapeutic options that may prolong overall survival and may not cross the blood-brain barrier could also lead to an increase in brain metastases in patients with ovarian cancer.

摘要

目的

利用真实世界数据评估卵巢癌患者发生脑转移的风险,并评估 BRCA 突变是否会增加这种风险。

方法

本回顾性研究纳入了 2011 年 1 月 1 日至 2018 年 1 月 31 日期间,来自 Flatiron Health 数据库的 4515 例卵巢癌患者。Flatiron Health 数据库是一个源自美国电子健康记录的、具有纵向、人口统计学和地域多样性的数据库。

结果

46(1%)例患者在诊断为卵巢癌后被诊断为脑转移。在 4515 例卵巢癌患者中,10%有已知的 BRCA 突变,37%为 BRCA 野生型(BRCAwt),其余 51%的 BRCA 状态未知/未经检测。与 BRCAwt 患者(0.6%)相比,BRCA 突变患者中观察到脑转移的比例为 3%。BRCA 突变患者中有 5.7%的患者在诊断后 5 年内发生脑转移,而 BRCAwt 患者中有 1.4%的患者发生脑转移(风险比 4.44;95%置信区间,1.97,10.00;P<0.0001)。这些数据表明,BRCA 突变患者发生脑转移的风险明显高于无突变者。

结论

尽管脑转移是卵巢癌的罕见表现,但应考虑这些患者发生脑转移的可能性,尤其是 BRCA 突变患者。新的治疗选择可能延长总生存期且不会穿透血脑屏障,这也可能导致卵巢癌患者的脑转移增加。

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