Fan Kevin Yijun, Chehade Rania, Fernandes Italo, Moravan Veronika, Sahgal Arjun, Warner Ellen, Jerzak Katarzyna Joanna
University of Toronto, Toronto, ON, Canada.
Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
JCO Precis Oncol. 2025 Mar;9:e2400641. doi: 10.1200/PO-24-00641. Epub 2025 Mar 6.
Human epidermal growth factor receptor 2 (HER2)-low is a newly defined subgroup of HER2-negative breast cancer. It is unknown whether HER2-low status is associated with brain metastases (BrM) development. We aimed to determine the association between HER2-low status and the time to developing BrM.
HER2 status was determined in a cohort of 689 women with metastatic breast cancer (MBC) who underwent treatment for BrM at Sunnybrook Odette Cancer Centre from 2008 to 2018. In patients with primary breast cancer (PBC) HER2 subclassification available (subgroup 1), we investigated time from PBC diagnosis to BrM diagnosis (PBC-time to brain metastases [TTBM]). In patients with HER2 subclassification available in any tissue (subgroup 2), we investigated time from MBC diagnosis to BrM diagnosis (MBC-TTBM).
In subgroup 1 (n = 175), patients with HER2-low disease (n = 42) had a shorter PBC-TTBM compared with those with HER2-zero disease (n = 77; hazard ratio, 2.4; = .0003). When stratified by hormone receptor (HR) status, this observation held true in the HR+/HER2- population, but not in the triple-negative breast cancer (TNBC) population. In subgroup 2 (n = 279), patients with HER2-low disease (n = 53) had a shorter MBC-TTBM compared to those with HER2-zero disease (n = 44) in the HR+/HER2- population (hazard ratio, 1.55; = .036); however, this did not hold true in the TNBC population. Likelihood ratio test revealed significant interaction between HER2 and HR status in subgroup 2 ( = .016), but not subgroup 1 ( = .21).
Our findings suggest that among patients with HR+ breast cancer, HER2-low status was associated with shorter TTBM compared with HER2-zero status. In a subset of patients for whom HER2 status of the PBC was available, HER2-low status was associated with shorter PBC-TTBM, irrespective of HR status. This study suggests a previously unrecognized association between HER2-low status and timing of BrM development.
人表皮生长因子受体2（HER2）低表达是HER2阴性乳腺癌新定义的一个亚组。HER2低表达状态是否与脑转移（BrM）的发生相关尚不清楚。我们旨在确定HER2低表达状态与发生BrM的时间之间的关联。
对2008年至2018年在桑尼布鲁克奥黛特癌症中心接受BrM治疗的689例转移性乳腺癌（MBC）女性患者队列进行HER2状态测定。在有原发性乳腺癌（PBC）HER2亚分类信息的患者（亚组1）中，我们研究了从PBC诊断到BrM诊断的时间（PBC至脑转移的时间[TTBM]）。在任何组织中有HER2亚分类信息的患者（亚组2）中，我们研究了从MBC诊断到BrM诊断的时间（MBC-TTBM）。
在亚组1（n = 175）中，HER2低表达疾病患者（n = 42）的PBC-TTBM比HER2零表达疾病患者（n = 77）短（风险比，2.4；P = .0003）。按激素受体（HR）状态分层时，这一观察结果在HR+/HER2-人群中成立，但在三阴性乳腺癌（TNBC）人群中不成立。在亚组2（n = 279）中，HR+/HER2-人群中HER2低表达疾病患者（n = 53）的MBC-TTBM比HER2零表达疾病患者（n = 44）短（风险比，1.55；P = .036）；然而，在TNBC人群中并非如此。似然比检验显示亚组2中HER2与HR状态之间存在显著交互作用（P = .016），但亚组1中不存在（P = .21）。
我们的研究结果表明，在HR+乳腺癌患者中，与HER2零表达状态相比，HER2低表达状态与较短的TTBM相关。在一部分有PBC的HER2状态信息的患者中，HER2低表达状态与较短的PBC-TTBM相关，与HR状态无关。本研究提示HER2低表达状态与BrM发生时间之间存在此前未被认识到的关联。
