Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Frauenärzte am Dom, Mainz, HELIOS Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany.
ESMO Open. 2022 Jun;7(3):100495. doi: 10.1016/j.esmoop.2022.100495. Epub 2022 May 30.
Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital.
A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype.
Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups.
We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.
多达 40%的转移性人表皮生长因子受体 2（HER2）阳性乳腺癌患者会发展为脑转移（BMs）。了解这些 HER2 阳性乳腺癌伴 BMs 患者的临床特征至关重要。
本分析共纳入来自脑转移乳腺癌登记处的 2948 例患者，其中 1311 例原发性肿瘤为 HER2 阳性亚型。
与 HER2 阴性患者相比，HER2 阳性乳腺癌伴 BMs 患者在乳腺癌和 BMs 诊断时年龄稍轻，新辅助化疗后病理完全缓解率更高，肿瘤分级更高。此外，与 HER2 阴性患者相比，HER2 阳性患者在 BMs 诊断时远处转移更不常见。HER2 阳性患者的 BMs 更常位于后颅窝，但脑膜转移较少见。所有 HER2 阳性患者的中位总生存期（OS）为 13.2 个月（95%置信区间 11.4-14.4）。以下因素与较短的 OS 相关（多因素分析）：BMs 诊断时年龄较大（≥60 岁与<60 岁：风险比[HR] 1.63，P<0.001）、东部合作肿瘤学组（ECOG）状态较低（2-4 级与 0-1 级：HR 1.59，P<0.001）、BMs 数量较多（2-3 个与 1 个：HR 1.30，P=0.082；≥4 个与 1 个：HR 1.51，P=0.004；全局 P=0.015）、前颅窝 BMs（HR 1.71，P<0.001）、脑膜转移（HR 1.63，P=0.012）、BMs 诊断时症状性（HR 1.35，P=0.033）和 BMs 诊断时远处转移（HR 1.43，P=0.020）。BMs 诊断后应用靶向治疗（HR 0.62，P<0.001）与更长的 OS 相关。HER2 阳性/激素受体阳性患者的 OS 长于 HER2 阳性/激素受体阴性患者（中位 14.3 与 10.9 个月；HR 0.86，P=0.03），但两组之间无无进展生存期差异。
我们确定了与 HER2 阳性伴 BMs 患者预后相关的因素。需要进一步研究以了解决定 HER2 阳性/激素受体阳性患者生存时间延长的因素。
