Germline BRCA mutation does not prevent response to taxane-based therapy for the treatment of castration-resistant prostate cancer
Germline BRCA mutation does not prevent response to taxane-based therapy for the treatment of castration-resistant prostate cancer
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DOI：
10.1111/j.1464-410x.2011.10292.x
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发表时间：
2012-03-01
影响因子：
4.5
通讯作者：
Robson, Mark E.
中科院分区：
文献类型：
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作者：
Gallagher, David J.;Cronin, Angel M.;Robson, Mark E.
目的 探讨 BRCA 突变状态与紫杉烷类化疗反应之间的关系，因为患有 BRCA 突变的前列腺癌携带者的生存率似乎比非携带者差，而多西他赛可改善去势抵抗性前列腺癌患者的生存率。 患者和方法我们确定了 158 名患有去势抵抗性前列腺癌的德系犹太人 (AJ) 男性中 BRCA 突变的患病率。临床数据作为机构前列腺癌研究数据库的一部分并通过额外的医疗记录审查进行收集。临床记录和 DNA 样本通过唯一标识符链接起来，在 AJ BRCA1/2 创建者突变基因检测之前对样本进行匿名化。对基于紫杉烷的治疗的反应由治疗 12 周内前列腺特异性抗原最低点来定义。结果 总共 88 名男性接受了基于紫杉烷的治疗，其中 7 名是 BRCA 携带者（3 名 BRCA1，4 名 BRCA2；5 名 BRCA 携带者）。 8%）。所有 7 名 BRCA 携带者和 69 名非携带者均对紫杉烷有初步反应。总体而言，71% (54/76) 的患者对治疗有反应，携带者 (57%) 和非携带者 (72%) 之间没有显着差异（绝对差异 15%；95% 置信区间 -23% 至 53%；P = 0.4）。在具有初始反应的患者中，前列腺特异性抗原的中位变化与BRCA 携带者（-63%，四分位间距 -71% 至 -57%）和非携带者（-60%，四分位间距 -78% 至 -35%）（P = 0.6）。在最后一次随访中，所有 7 名 BRCA 携带者和 49 名非携带者均死于前列腺癌。一名 BRCA2 携带者接受多西紫杉醇加铂治疗，存活了 37 个月。 结论 在这项小型假设生成研究中，大约一半的 BRCA 携带者对基于紫杉烷的化疗有前列腺特异性抗原反应，这表明对于这些个体来说，这是一种积极的疗法。
OBJECTIVETo investigate the relationship between BRCA mutation status and response to taxane-based chemotherapy, since BRCA mutation carriers with prostate cancer appear to have worse survival than non-carriers and docetaxel improves survival in patients with castration-resistant prostate cancer.PATIENTS AND METHODSWe determined BRCA mutation prevalence in 158 Ashkenazi Jewish (AJ) men with castration-resistant prostate cancer. Clinical data were collected as part of an institutional prostate cancer research database and through additional medical record review.Clinical records and DNA samples were linked through a unique identifier, anonymizing the samples before genetic testing for the AJ BRCA1/2 founder mutations.Response to taxane-based therapy was defined by the prostate-specific antigen nadir within 12 weeks of therapy.RESULTS In all, 88 men received taxane-based treatment, seven of whom were BRCA carriers (three BRCA1, four BRCA2; 8%). Initial response to taxane was available for all seven BRCA carriers and for 69 non-carriers.Overall, 71% (54/76) of patients responded to treatment, with no significant difference between carriers (57%) and non-carriers (72%) (absolute difference 15%; 95% confidence interval -23% to 53%; P = 0.4).Among patients with an initial response, the median change in prostate-specific antigen was similar for BRCA carriers (-63%, interquartile range -71% to -57%) and non-carriers (-60%, interquartile range -78% to -35%) (P = 0.6).At last follow-up, all seven BRCA carriers and 49 non-carriers had died from prostate cancer. One BRCA2 carrier treated with docetaxel plus platinum survived 37 months.CONCLUSIONIn this small, hypothesis-generating study approximately half of BRCA carriers had a prostate-specific antigen response to taxane-based chemotherapy, suggesting that it is an active therapy in these individuals.