JCO：卵巢癌生殖系BRCA1/2测试

近日，科学家建议无论家族史情况如何，诊断患有非黏液性卵巢癌妇女进行生殖系BRCA1/2测试，相关研究论文刊登在Journal of Clinical Oncology杂志上。

为了研究生殖系BRCA1/2突变对卵巢癌的作用，澳大利亚墨尔本东中彼得麦卡勒姆癌症中心Kathryn Alsop等人进行了一项病例对照研究，该研究纳入筛选出的1001名非黏液性卵巢癌妇女，科学家研究分析了生殖系的BRCA1和BRCA2基因突变情况。

研究人员发现14.1％的患者表现出BRCA1/ 2生殖系突变。其中，16.6％的有浆液性癌和44％患者没有任何乳腺癌或卵巢癌家族史。没有生殖系突变的妇女患者，卵巢癌疾病无进展，总生存期也有所改善。

我们的研究结果中所有侵入性卵巢癌患者的基因检测的结果表明BRCA状态的测量非常重要，应该进入临床常用检测指标之列。

doi:10.1200/JCO.2011.39.8545
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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

Kathryn Alsop, Sian Fereday, Cliff Meldrum, Anna deFazio, Catherine Emmanuel, Joshy George, et al.

Purpose The 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 Methods Women 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.

Results Germ-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.

Conclusion BRCA 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.