Rudat Volker, El-Sweilmeen Hamdan, Brune-Erber Iris, Nour Alaa Ahmad, Almasri Nidal, Altuwaijri Saleh, Fadel Elias
Department of Radiation Oncology, Saad Specialist Hospital, P,O, Box 30353, Al Khobar 31952, Saudi Arabia.
BMC Cancer. 2014 Apr 24;14:289. doi: 10.1186/1471-2407-14-289.
The objective of this study was to identify breast cancer patients with a high risk of developing brain metastases who may benefit from pre-emptive medical intervention.
Medical records of 352 breast cancer patients with local or locoregional disease at diagnosis were retrospectively analysed. The brain metastasis-free survival was estimated using the Kaplan-Meier method and patient groups were compared using the log rank test. The simultaneous relationship of multiple prognostic factors was assessed using Cox's proportional hazard regression analysis. The Fisher exact test was used to test the difference of proportions for statistical significance.
On univariate analysis, statistically highly significant unfavourable risk factors for the brain metastasis-free survival were negative ER status, negative PR status, and triple negative tumor subtype. Young age at diagnosis (≤35 years) and advanced disease stage were not statistically significant (p = 0.10). On multivariate analysis, the only independent significant factor was the ER status (negative ER status; hazard radio (95% confidence interval), 5.1 (1.8-14.6); p = 0.003). In the subgroup of 168 patients with a minimum follow-up of 24 months, 49 patients developed extracranial metastases as first metastatic event. Of those, 7 of 15 (46.6%) with a negative ER status developed brain metastases compared to 5 of 34 (14.7%) with a positive ER status (Fisher exact test, p = 0.03). The median time interval (minimum-maximum) between the diagnosis of extracranial and brain metastases was 7.5 months (1-30 months).
Breast cancer patients with extracranial metastasis and negative ER status exhibited an almost 50% risk of developing brain metastasis during their course of disease. Future studies are highly desired to evaluate the efficacy of pre-emptive medical intervention such as prophylactic treatment or diagnostic screening for high risk breast cancer patients.
本研究的目的是识别可能从先发制性医学干预中获益的、发生脑转移风险较高的乳腺癌患者。
对352例诊断时患有局部或区域局部疾病的乳腺癌患者的病历进行回顾性分析。采用Kaplan-Meier法估计无脑转移生存期,并使用对数秩检验比较患者组。使用Cox比例风险回归分析评估多个预后因素的同时关系。采用Fisher精确检验来检验比例差异的统计学显著性。
单因素分析显示,无脑转移生存期的统计学上高度显著的不利风险因素为雌激素受体(ER)状态阴性、孕激素受体(PR)状态阴性和三阴性肿瘤亚型。诊断时年龄较小(≤35岁)和疾病晚期在统计学上无显著意义(p = 0.10)。多因素分析显示,唯一独立的显著因素是ER状态(ER状态阴性;风险比(95%置信区间),5.1(1.8 - 14.6);p = 0.003)。在168例至少随访24个月的患者亚组中,49例患者发生颅外转移作为首个转移事件。其中,ER状态阴性的15例中有7例(46.6%)发生脑转移,而ER状态阳性的34例中有5例(14.7%)发生脑转移(Fisher精确检验,p = 0.03)。颅外转移和脑转移诊断之间的中位时间间隔(最小值 - 最大值)为7.5个月(1 - 30个月)。
发生颅外转移且ER状态阴性的乳腺癌患者在病程中发生脑转移的风险近50%。非常需要未来的研究来评估先发制性医学干预(如预防性治疗或对高危乳腺癌患者进行诊断性筛查)的疗效。