【原】皇马：转移性乳腺癌继发软脑膜病的治疗和预后

　　软脑膜病是晚期乳腺癌的罕见并发症，其预后不良，虽然放疗、全身和鞘内化疗均为公认治疗方式，但是疗效数据有限。

　　2017年9月29日，欧洲乳腺癌专科学会《乳腺》在线发表英国皇家马斯登医院的研究报告，评估了该患者组的可能预测因素。

英国皇家马斯登医院：全世界成立最早、目前欧洲规模最大的癌症诊断治疗教学研究中心（其地位如同足球界的皇家马德里），由外科医生威廉·马斯登创建于1851年，现为伦敦大学癌症研究院、伦敦帝国学院的教学医院。

　　该研究根据电子病历确定10年期间（2004年1月～2014年1月）经磁共振成像确诊为软脑膜病的乳腺癌患者，使用生存曲线估算无进展生存和总生存，并按治疗方式进行预设亚组分析，使用多因素比例风险回归模型确定显著预后因素。

　　结果共确定182例符合条件的患者，均为女性，确诊软脑膜病时中位年龄52.5岁（范围23～80）。其中：

• 90例（49.5%）ER阳性HER2阴性

• 48例（26.4%）HER2阳性

• 27例（14.8%）三阴性

• 17例（12.5%）HER2不详

　　软脑膜病的常用初始疗法：

• 脑部放疗：62例（34.1%）

• 全身治疗：45例（24.7%）

• 支持治疗：37例（20.3%）

• 鞘内化疗：14例（7.7%）

• 鞘内注射曲妥珠单抗：2例

　　从软脑膜病诊断开始计算：

• 无进展生存3.9个月（95%CI：3.2～5.0）

• 中位总生存5.4个月（95%CI：4.2～6.6）

　　不同治疗方式的中位总生存：

• 全身治疗：8.8个月（95%CI：5.5～11.1）

• 脑部放疗：6.1个月（95%CI：4.2～7.9）

• 鞘内治疗；2.9个月（95%CI：1.2～5.8）

• 支持治疗；1.7个月（95%CI：0.9～3.0）

　　根据多因素分析，以下因素与总生存差显著相关：

• 三阴性（风险比：2.08，P=0.007）

• 伴脑转移（风险比：1.74，P=0.006）

• 累及脑和脊髓（风险比：2.81，P<0.001）

　　因此，三阴性、伴脑转移、同时累及脑和脊髓的乳腺癌继发软脑膜病患者预后最差，迫切需要临床研究确定这些患者的更有效治疗方法。

Breast. 2017 Sep 29;36:54-59. [Epub ahead of print]

Treatment and prognosis of leptomeningeal disease secondary to metastatic breast cancer: A single-centre experience.

Belinda Kingston, Hamzeh Kayhanian, Chloe Brooks, Nicola Cox, Narda Chaabouni, Stefania Redana, Eleftheria Kalaitzaki, Ian Smith, Mary O'Brien, Stephen Johnston, Marina Parton, Jill Noble, Susie Stanway, Alistair Ring, Nicholas Turner, Alicia Okines.

The Royal Marsden NHS Foundation Trust, London and Surrey, UK.

PURPOSE: Leptomeningeal disease (LMD) is an uncommon complication of advanced breast cancer. The prognosis is poor, and although radiotherapy (RT), systemic and intra-thecal (IT) chemotherapy are accepted treatment modalities, efficacy data are limited. This study was designed to evaluate potential predictors of survival in this patient group.

METHODS: Breast cancer patients with LMD diagnosed by MRI in a 10-year period (2004-2014) were identified from electronic patient records. PFS and OS estimates were calculated using Kaplan-Meier method, with planned sub-group analysis by treatment modality. Cox regression was employed to identify significant prognostic variables.

RESULTS: We identified 182 eligible patients; all female, median age at LMD diagnosis 52.5 years (range 23-80). Ninety patients (49.5%) were ER positive/HER2 negative; 48 (26.4%) were HER2 positive, and 27 (14.8%) were triple negative. HER2 status was unknown in 17 (9.3%). Initial management of LMD was most commonly whole or partial brain RT in 62 (34.1%), systemic therapy in 45 (24.7%) or supportive care alone in 37 (20.3%). Fourteen patients (7.7%) underwent IT chemotherapy, of whom two also received IT trastuzumab. From diagnosis of LMD, the median PFS was 3.9 months (95%CI 3.2-5.0) and median OS was 5.4 months (95%CI 4.2-6.6). Patients treated with systemic therapy had the longest OS (median 8.8 months, 95%CI 5.5-11.1), compared to RT; 6.1 months (95%CI 4.2-7.9 months), IT therapy; 2.9 months (95%CI 1.2-5.8) and supportive care; 1.7 months (95%CI 0.9-3.0). On multivariable analysis, triple negative histology, concomitant brain metastases, and LMD involving both the brain and spinal cord were associated with poor OS.

CONCLUSIONS: Breast cancer patients with triple negative LMD, concomitant brain metastases or LMD affecting both the spine and brain have the poorest prognosis. Clinical trials to identify more effective treatments for these patients are urgently needed.

KEYWORDS: Breast cancer; Leptomeningeal disease; Presentation; Survival; Prognostic factors

DOI: 10.1016/j.breast.2017.07.015