PO.CL09.02 · 临床研究
ER-low乳腺癌脑转移的发生率与结局：来自美国国家癌症数据库（NCDB）的见解
Incidence and outcomes of brain metastasis in ER-low breast cancer: Insights from a National Cancer Database (NCDB)
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：脑转移（BrM）是一种侵袭性且危及生命的并发症，在三阴性和HER2阳性乳腺癌中发生更为频繁。雌激素受体（ER）阳性的最佳临界值已被讨论超过十年。新兴数据提示，ER-low（1-10% ER染色）乳腺癌表现出与ER阴性肿瘤更接近的临床和生物学特征，这凸显了研究ER-low肿瘤中脑转移发生率的必要性，以更好地识别高危人群并优化未来临床试验的患者选择。
方法：使用2022年NCDB参与者用户文件进行了一项回顾性队列研究。我们收集了2018-2022年间新发IV期乳腺癌患者，因为2018年是ER首次被定义为连续变量、允许对ER进行分类的第一年。ER状态分为ER<1%（阴性）、1-10%（低）和>10%（阳性）。人口统计学、临床病理和治疗变量在各ER组间进行比较，分类变量采用卡方检验或Fisher精确检验，连续变量采用t检验或Kruskal-Wallis检验。使用单变量logistic回归评估ER状态与诊断时脑转移（BrM）（有vs无）之间的关联。对有BrM的患者，使用Cox比例风险模型评估总生存期（OS）。
结果：共纳入18,783例患者。多数年龄为60-69岁（30.5%），77.0%为白人，85.0%为浸润性导管癌，51.7%为3级组织学。ER状态阴性者占23.0%，低者占3.1%，阳性者占73.9%。HER2状态阴性者占70.2%，低者占10.7%，阳性者占14.5%，未知者占4.6%。总体而言，7.3%的患者在基线时有BrM。ER阴性（12.0%）和ER-low（10.0%）肿瘤的BrM高于ER阳性疾病（5.7%）[比值比：ER阴性2.24（95% CI：2-2.52），ER-low 1.82（95% CI：1.38-2.41），与ER阳性相比]（单变量logistic回归）。有BrM患者的OS在各组间相似（ER阴性HR 0.93 [0.71-1.22]，ER-low HR 0.91 [0.43-1.93]，与ER阳性相比）。
结论：ER-low乳腺癌诊断时BrM的比例与ER阴性疾病比与ER阳性疾病更为相似。然而，脑转移患者的OS在所有ER亚型中同样不佳，提示一旦发生脑侵犯，潜在的组织学对预后影响有限。这些发现凸显了ER-low和ER阴性疾病相似的临床特征，强化了对神经系统症状的及时评估，并鼓励在BrM特异性临床试验中更多地纳入该亚组。
查看英文原文 English abstract
Background: Brain metastases (BrM) are aggressive and life-limiting complications that occur more frequently in triple-negative and HER2-positive breast cancers. The optimal cut-off value of estrogen receptor (ER) positivity has been under discussion for over a decade. Emerging data suggest that ER-low (1-10% ER staining) breast cancers exhibit clinical and biological features closer to ER-negative tumors, underscoring the need to investigate the incidence of brain metastasis among ER-low tumors to better identify high-risk populations and optimize patient selection for future clinical trials.
Methods: A retrospective cohort study was performed using the 2022 NCDB Participant User File. We collected patients with de novo stage IV breast cancer from 2018-2022, as 2018 was the first year that ER was defined as a continuous variable allowing categorization of ER. ER status was categorized as ER <1% (negative), 1-10% (low), and >10% (positive). Demographic, clinicopathologic, and treatment variables were compared across ER groups using chi-square or Fisher's exact tests for categorical variables and t-test or Kruskal-Wallis tests for continuous variables. Associations between ER status and brain metastases (BrM) at diagnosis (yes vs no) were evaluated using univariate logistic regression. Overall survival (OS) was assessed using cox proportional hazards model for patients who had BrM.
Results: A total of 18,783 patients were included in the analysis. Most were aged 60-69 years (30.5%), 77.0% were White, 85.0% had infiltrating ductal carcinoma, and 51.7% had grade 3 histology. ER status was negative in 23.0%, low in 3.1%, and positive in 73.9%. HER2 status was negative in 70.2%, low in 10.7%, positive in 14.5%, and unknown in 4.6%. Overall, 7.3% of patients had BrM at baseline. BrM were higher in ER-negative (12.0%) and ER-low (10.0%) tumors vs ER-positive disease (5.7%) [Odds ratio: ER-negative; 2.24 (95% CI: 2-2.52), ER-low; 1.82 (95%CI: 1.38-2.41) compared to ER-positive] in univariate logistic regression. OS among patients with BrM was similar between groups (ER-negative; HR 0.93 [0.71-1.22], ER-low; HR 0.91 [0.43-1.93] compared to ER-positive).
Conclusions: The proportion of BrM at diagnosis in ER-low breast cancer was more similar to ER-negative than ER-positive disease. However, the OS in patients with brain metastasis was similarly poor across all ER subtypes, suggesting that once brain involvement occurs, underlying histology has limited prognostic impact. These findings highlight the similar clinical features of ER-low and ER-negative disease, reinforce prompt evaluation of neurologic symptoms, and encourage greater inclusion of this subgroup in BrM-specific clinical trials.
利益披露 Disclosure
A. B. Warner,
DeLoitte Consulting Independent Contractor.
J. Perkins, None..
M. Nealeigh, None..
T. Fujii, None.