BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation-Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group
BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation-Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group
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DOI：
10.1200/jco.2011.39.8545
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发表时间：
2012-07-20
影响因子：
45.3
通讯作者：
Mitchell, Gillian
中科院分区：
文献类型：
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作者：
Alsop, Kathryn;Fereday, Sian;Mitchell, Gillian
目的卵巢癌患者BRCA 1和BRCA 2生殖系突变的频率尚不清楚，报道的频率从3%到27%不等。生殖系突变的反应的影响，需要进一步调查，以了解其对治疗计划和临床试验design.Patients和MethodsWomen的影响非粘液性卵巢癌（n = 1,001）入组到一个以人群为基础的病例对照研究进行了筛选点突变和两个基因的大缺失。多线化疗的生存结果和反应进行了assessed.ResultsGerm-line突变被发现在14.1%的患者整体，包括16.6%的浆液性癌症患者（高级别浆液性，22.6%）; 44%没有乳腺癌或卵巢癌的家族史。携带生殖系突变的患者的无进展生存率和总生存率提高。在复发情况下，携带突变的患者对铂类和非铂类方案的反应比突变阴性患者更频繁，即使在初次治疗后早期复发的患者中也是如此。突变阴性的患者谁回应了多个周期的铂为基础的治疗更容易携带体细胞BRCA 1/2 mutations.ConclusionBRCA突变状态有重大影响，卵巢癌患者的生存，并应在临床试验中的一个额外的分层因素。BRCA 1/2携带者的治疗结果对铂类耐药的传统定义提出了挑战，突变状态可能有助于复发情况下的决策和全身治疗选择。我们的数据，加上聚（ADP-核糖）聚合酶抑制剂试验的出现，支持生殖系BRCA 1/2检测应提供给所有诊断为非粘液性卵巢癌的妇女，无论家族史的建议。
PurposeThe frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design.Patients and MethodsWomen with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed.ResultsGerm-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-grade serous, 22.6%); 44% had no reported family history of breast or ovarian cancer. Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin- based treatment were more likely to carry somatic BRCA1/2 mutations.ConclusionBRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history.