Overall Survival and the Response to Radiotherapy Among Molecular Subtypes of Breast Cancer Brain Metastases Treated With Targeted Therapies

被引：56

作者：

Miller, Jacob A. ^{[2
]}

Kotecha, Rupesh ^{[1
]}

Ahluwalia, Manmeet S. ^{[2
,3
,4
]}

Mohammadi, Alireza M. ^{[2
,3
,5
]}

Chao, Samuel T. ^{[1
,2
,3
]}

Barnett, Gene H. ^{[2
,3
,5
]}

Murphy, Erin S. ^{[1
,2
,3
]}

Vogelbaum, Michael A. ^{[2
,3
,5
]}

Angelov, Lilyana ^{[2
,3
,5
]}

Peereboom, David M. ^{[2
,3
,4
]}

Suh, John H. ^{[1
,2
,3
]}

机构：

[1] Cleveland Clin, Taussig Canc Inst, Dept Radiat Oncol, T28,9500 Euclid Ave, Cleveland, OH 44195 USA

[2] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA

[3] Cleveland Clin, Rose Ella Burkhardt Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA

[4] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol, Cleveland, OH 44106 USA

[5] Cleveland Clin, Dept Neurosurg, Neurol Inst, Cleveland, OH 44106 USA

来源：

CANCER | 2017年 / 123卷 / 12期

关键词：

brain metastasis; breast cancer; human epidermal growth factor receptor 2 (HER2); hormone receptor; lapatinib; radiation necrosis; stereotactic radiosurgery; LAPATINIB PLUS CAPECITABINE; NERVOUS-SYSTEM METASTASES; GRADED PROGNOSTIC ASSESSMENT; STEREOTACTIC RADIOSURGERY; TRASTUZUMAB EMTANSINE; RADIATION NECROSIS; COMPETING RISK; PHASE-III; RECURRENCE; CARCINOMA;

D O I：

10.1002/cncr.30616

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. METHODS: Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. RESULTS: Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P=.04) and TKIs (21.1 months vs 15.4 months; P=.03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P=.01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). CONCLUSIONS: Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2-directed therapy in the HER2-amplified population, reserving whole-brain radiotherapy for salvage. (C) 2017 American Cancer Society.

引用

页码：2283 / 2293

页数：11