Background: Breast cancer is the second most common cause of brain metastases (BM). Despite increasing incidence of BM in older women, there are limited data on the optimal management of BM in this age group. In this study, we assessed the survival outcomes and treatment patterns of older breast cancer patients ≥65 years old with BM compared to younger patients at our institution. Methods: An IRB-approved single-institutional retrospective review of biopsy-proven breast cancer patients with BM treated with 1- to 5-fraction stereotactic radiation therapy (SRS) from 2015 to 2020 was performed. Primary endpoint was intracranial progression-free survival (PFS) defined as the time interval between the end of SRS to the date of the first CNS progression. Secondary endpoints were overall survival (OS) from the end of SRS and radiation treatment patterns. Kaplan–Meier estimates and Cox proportional hazard regression method were used for survival analyses. Results: A total of 112 metastatic breast cancer patients with BMs were included of which 24 were ≥65 years old and 88 were <65 years old. Median age at RT was 72 years (range 65–84) compared to 52 years (31–64) in younger patients. There were significantly higher number of older women with ER/PR positive disease (75% vs. 49%,p= 0.036), while younger patients were more frequently triple negative (32% vs. 12%,p= 0.074) and HER2 positive (42% vs. 29%,p= 0.3). Treatment-related adverse events were similar in both groups. Overall, 14.3% patients had any grade radiation necrosis (RN) (older vs. young: 8.3% vs. 16%,p= 0.5) while 5.4% had grade 3 or higher RN (0% vs. 6.8%,p= 0.7). Median OS after RT was poorer in older patients compared to younger patients (9.5 months vs. 14.5 months,p= 0.037), while intracranial PFS from RT was similar between the two groups (9.7 months vs. 7.1 months,p= 0.580). On univariate analysis, significant predictors of OS were age ≥65 years old (hazard risk, HR = 1.70,p= 0.048), KPS ≤ 80 (HR = 2.24,p< 0.001), HER2 positive disease (HR = 0.46,p< 0.001), isolated CNS metastatic disease (HR = 0.29,p< 0.001), number of brain metastases treated with RT (HR = 1.06,p= 0.028), and fractionated SRS (HR = 0.53,p= 0.013). On multivariable analysis, KPS ≤ 80, HER2 negativity and higher number of brain metastases predicted for poorer survival, while age was not a significant factor for OS after adjusting for other variables. Patients who received systemic therapy after SRS had a significantly improved OS on univariate and multivariable analysis (HR = 0.32,p< 0.001). Number of brain metastases treated was the only factor predictive of worse PFS (HR = 1.06,p= 0.041), which implies a 6% additive risk of progression for every additional metastasis treated. Conclusions: Although older women had poorer OS than younger women, OS was similar after adjusting for KPS, extracranial progression, and systemic therapy; and there was no difference in rates of intracranial PFS, neurological deaths, and LMD in the different age groups. This study suggests that age alone may not play an independent role in treatment-selection and that outcomes for breast cancer patients with BMs and personalized decision-making including other clinical factors should be considered. Future studies are warranted to assess neurocognitive outcomes and other radiation treatment toxicities in older patients.
背景：乳腺癌是导致脑转移（BM）的第二大常见原因。尽管老年女性BM发病率不断上升，但针对该年龄组BM最佳治疗策略的数据仍有限。本研究旨在评估本机构中≥65岁老年乳腺癌脑转移患者与年轻患者的生存结局及治疗模式差异。 方法：本研究经机构审查委员会批准，对2015年至2020年间经活检确诊、接受1-5次立体定向放射治疗（SRS）的乳腺癌脑转移患者进行单中心回顾性分析。主要终点为颅内无进展生存期（PFS），定义为从SRS治疗结束至首次中枢神经系统进展的时间间隔。次要终点包括SRS治疗后的总生存期（OS）及放射治疗模式。采用Kaplan-Meier估计法和Cox比例风险回归模型进行生存分析。 结果：共纳入112例乳腺癌脑转移患者，其中24例≥65岁，88例<65岁。老年组放疗中位年龄为72岁（范围65-84岁），年轻组为52岁（范围31-64岁）。老年组雌激素受体/孕激素受体阳性患者比例显著更高（75% vs. 49%，p=0.036），而年轻组三阴性（32% vs. 12%，p=0.074）和HER2阳性（42% vs. 29%，p=0.3）患者更常见。两组治疗相关不良事件发生率相似：总体14.3%患者出现任何级别的放射性坏死（老年组vs.年轻组：8.3% vs. 16%，p=0.5），5.4%出现3级及以上放射性坏死（0% vs. 6.8%，p=0.7）。老年组放疗后中位OS较年轻组更差（9.5个月 vs. 14.5个月，p=0.037），而两组放疗后颅内PFS无显著差异（9.7个月 vs. 7.1个月，p=0.580）。单因素分析显示，OS的显著预测因素包括：年龄≥65岁（风险比HR=1.70，p=0.048）、KPS≤80分（HR=2.24，p<0.001）、HER2阳性疾病（HR=0.46，p<0.001）、孤立性中枢神经系统转移（HR=0.29，p<0.001）、放疗治疗的脑转移灶数量（HR=1.06，p=0.028）以及分次SRS治疗（HR=0.53，p=0.013）。多变量分析显示，在校正其他变量后，KPS≤80分、HER2阴性及更多脑转移灶数量是生存较差的预测因素，而年龄对OS无显著影响。单因素及多变量分析均证实，SRS后接受全身治疗的患者OS显著改善（HR=0.32，p<0.001）。放疗治疗的脑转移灶数量是PFS较差的唯一预测因素（HR=1.06，p=0.041），提示每增加一个转移灶，进展风险增加6%。 结论：尽管老年女性OS较年轻女性更差，但在校正KPS评分、颅外进展及全身治疗后，两组OS相似；且不同年龄组在颅内PFS、神经性死亡和软脑膜转移发生率方面无差异。本研究表明，年龄本身可能并非治疗选择的独立影响因素，乳腺癌脑转移患者的治疗决策应结合其他临床因素进行个体化考量。未来需进一步研究评估老年患者的神经认知结局及其他放射治疗毒性。
Stereotactic Radiosurgery for Women Older than 65 with Breast Cancer Brain Metastases
肿瘤(癌症)患者之家