Linderholm B, Tavelin B, Grankvist K, Henriksson R
Department of Oncology, Umeå University Hospital, Sweden.
Br J Cancer. 1999 Oct;81(4):727-32. doi: 10.1038/sj.bjc.6690755.
The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) content in 302 consecutive node-negative breast cancer (NNBC) patients treated with only locoregional radiotherapy to relapse free- (RFS) and overall survival (OS). VEGF content in tumour cytosols was measured by an enzymatic immunoassay for the major isoform VEGF165. The median age was 56 years, the median follow-up time 56 months. A wide range (0.01-144.79 pg microg(-1) DNA) of VEGF content was found (median 1.92). Significant associations were found between VEGF and oestrogen receptor (ER) content, progesterone receptor (PR) and tumour size (P = 0.005). Univariate analysis displayed significant reduced RFS and OS for patients with higher VEGF content (P = 0.0113 and P = 0.0075 respectively). A total of 43 recurrences have been found (ten local relapses within the breast, five in the axillary or supraclavicular lymph nodes and 28 distant metastasis). There was no significant correlation between the localization of the relapse and the VEGF content. Multivariate analysis suggested VEGF as the only predictor of OS (relative risk (RR) = 3.6, 95% confidence interval (CI) = 0.97-13.37), and in patients with T1 tumours (n = 236) the multivariate analysis clearly displayed VEGF as the only independent predictor of both RFS and OS (RR = 5.1, CI = 1.07-24.59). In the subgroup with ER-positive tumours (n = 229), multivariate analysis showed VEGF as the only significant predictor of RFS and OS (RR = 10.44, CI = 1.26-86.38). The results suggest VEGF165 as a predictor of RFS and OS in NNBC patients treated with locoregional radiotherapy, comprising especially patients with favourable prognosis of T1 tumours, or ER-positive tumours. The high VEGF expression might define a radioresistant phenotype, or indicate an early distant spread which might require adjuvant systemic treatment.
本研究旨在确定302例仅接受局部区域放疗的连续无淋巴结转移乳腺癌（NNBC）患者的血管内皮生长因子（VEGF）含量与无复发生存期（RFS）和总生存期（OS）之间的关联。通过酶免疫测定法检测肿瘤细胞溶质中主要异构体VEGF165的VEGF含量。中位年龄为56岁，中位随访时间为56个月。发现VEGF含量范围很广（0.01 - 144.79 pg μg(-1) DNA）（中位数为1.92）。发现VEGF与雌激素受体（ER）含量、孕激素受体（PR）和肿瘤大小之间存在显著关联（P = 0.005）。单因素分析显示，VEGF含量较高的患者RFS和OS显著降低（分别为P = 0.0113和P = 0.0075）。共发现43例复发（10例为乳腺内局部复发，5例为腋窝或锁骨上淋巴结复发，28例为远处转移）。复发部位与VEGF含量之间无显著相关性。多因素分析表明VEGF是OS的唯一预测因子（相对风险（RR）= 3.6，95%置信区间（CI）= 0.97 - 13.37），在T1肿瘤患者（n = 236）中，多因素分析清楚地显示VEGF是RFS和OS的唯一独立预测因子（RR = 5.1，CI = 1.07 - 24.59）。在ER阳性肿瘤亚组（n = 229）中，多因素分析显示VEGF是RFS和OS的唯一显著预测因子（RR = 10.44，CI = 1.26 - 86.38）。结果表明，VEGF165是接受局部区域放疗的NNBC患者RFS和OS的预测因子，尤其包括T1肿瘤或ER阳性肿瘤且预后良好的患者。高VEGF表达可能定义了一种放射抗性表型，或表明早期远处转移，这可能需要辅助全身治疗。
