Biological subtypes and survival outcomes in breast cancer patients with brain metastases in the targeted therapy era
Biological subtypes and survival outcomes in breast cancer patients with brain metastases in the targeted therapy era
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DOI：
10.1093/nop/npx033
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发表时间：
2018-09-01
影响因子：
2.7
通讯作者：
Prabhu, Sujit S.
中科院分区：
文献类型：
--
作者：
de Almeida Bastos, Dhiego Chaves;Calfat Maldaun, Marcos Vinicius;Prabhu, Sujit S.
背景人们认识到，乳腺癌是一组异质性疾病，根据激素受体（HR）和人表皮生长因子受体2（HER 2）状态等组合分子特征分为亚型。我们的目的是研究乳腺癌脑转移生物亚型的临床差异后，靶向治疗引入。这是一项回顾性研究，纳入了1998年至2013年在MD安德森癌症中心接受治疗的406例乳腺癌脑转移连续患者。总体而言，这些患者中有315例符合研究标准并进行了分析。亚型分为HER 2-/HR+（96例患者）、HER 2 +/HR+（57例患者）、HER 2 +/HR-（63例患者）和三阴性（HER 2-/HR-）（99例患者）。终点为发生脑转移的时间（TDBM）、无脑转移生存期（BMFS）和脑转移治疗开始后的总生存期（OSBM）。采用单因素和多因素考克斯比例风险回归模型进行分析。HER 2-/HR+的TDBM为41个月; HER 2 +/HR+为58个月; HER 2 +/HR-为30个月;三阴性为27个月（P < .001）。HER 2-/HR+的BMFS为9个月; HER 2 +/HR+为24个月; HER 2 +/HR-为9个月;三阴性为7个月（P = .06）。HER 2-/HR+的OSBM为20个月; HER 2 +/HR+为22个月; HER 2 +/HR-为24个月;三阴性为9个月（P < .001）。在多变量分析中，三阴性与其他亚型相比，OSBM较低，风险比为1.9（P < .001）。比较所有乳腺癌亚组，我们注意到HR和HER 2是脑转移行为中最重要的生物标志物。接受靶向治疗的患者有更好的结局，但三阴性组没有。建议对每个亚组进行不同治疗方式的前瞻性研究。
Background. There is recognition that breast cancer is a collection of heterogeneous diseases divided in subtypes based on combined molecular features such as hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status. We aimed to study clinical differences among biological subtypes in brain metastasis from breast cancer after targeted therapy introduction.Methods. This was a retrospective study with 406 consecutive patients with brain metastasis from breast cancer treated at MD Anderson Cancer Center from 1998 to 2013. Overall, 315 of these patients met the study criteria and were analyzed. Subtypes were classified as HER2-/HR+ (96 patients), HER2+/HR+ (57 patients), HER2+/HR- (63 patients), and triple negative (HER2-/HR-) (99 patients). End points were time to development of brain metastasis (TDBM), brain metastasis-free survival (BMFS), and overall survival from start of treatment of brain metastasis (OSBM). Univariate and multivariate Cox proportional hazard regression models were used to analyze the data.Results. TDBM was 41 months for HER2-/HR+; 58 months for HER2+/HR+; 30 months for HER2+/HR-; and 27 months for triple negative (P < .001). BMFS was 9 months for HER2-/HR+; 24 months for HER2+/HR+; 9 months for HER2+/HR-; and 7 months for triple negative (P = .06). OSBM was 20 months for HER2-/HR+; 22 months for HER2+/HR+; 24 months for HER2+/HR-; and 9 months for triple negative (P < .001). On multivariate analyses, triple negative showed lower OSBM compared with other subtypes, with a hazard ratio of 1.9 (P < .001).Conclusion. Comparing all breast cancer subgroups we noticed that HR and HER2 are the most significant biomarkers in brain metastasis behavior. Patients who received targeted therapy had better outcomes, but not in the triple negative group. Prospective studies with different treatment modalities for each subgroup are recommended.