脑转移大约占全部转移部位的7.56%，是乳腺癌患者死亡的重要原因。随着影像学的进步和全身治疗的发展，晚期乳腺癌患者脑转移比例增至30%，一年内死亡比例约为80%。不过，虽然脑转移比例正在增加，但是由于缺乏生存获益证据，现有乳腺癌指南不推荐常规筛查脑转移。因此，大多数脑转移是根据神经系统症状被发现，经常需要采取积极措施，例如手术或全脑放疗。目前，中国缺乏针对初诊乳腺癌时已发生脑转移的大样本研究，而涉及任何转移时期脑转移患者的小样本回顾研究结果不一。
2021年2月1日，欧洲乳腺癌专科医师学会《乳腺》正式发表中国医学科学院肿瘤医院李逸群、李俏、莫红楠、管秀雯、林少妍、王紫晶、陈怡萌、张烨、陈闪闪、蔡锐刚、王佳玉、罗扬、樊英、袁芃、张频、李青、马飞、徐兵河等学者的研究报告，分析了中国初诊乳腺癌患者脑转移的发生比例、风险因素、治疗方法和生存结局。
该单中心大样本回顾研究利用中国国家癌症中心数据库，确定2003～2015年初诊晚期乳腺癌患者2087例，提取临床病理特征、治疗方法和生存信息。通过多因素逻辑回归和多因素比例风险回归，分别确定晚期乳腺癌初诊时脑转移和生存结局的预测因素。
结果，初诊晚期乳腺癌时已发生脑转移患者90例（4.3%）
HR阳性HER2阴性乳腺癌：27例（2.5%）
HER2阳性乳腺癌：42例（7.2%）
三阴性乳腺癌：21例（5.2%）
初诊晚期乳腺癌时已发生脑转移的风险因素包括：
HER2阳性乳腺癌（比值比：2.38，95%置信区间：1.40～4.04，P<0.0001）
三阴性乳腺癌（比值比：1.89，95%置信区间：1.02～3.51，P=0.005）
骨、肝、肺三个部位全部转移（比值比：3.23，95%置信区间：1.52～6.87，P=0.002）
脑转移后中位总生存时间23.7个月（95%置信区间：15.9～31.5）。
对于HER2阳性乳腺癌，一线酪氨酸激酶抑制剂（拉帕替尼、吡咯替尼）与曲妥珠单抗治疗方案相比，中位总生存时间较长（44.9比35.4个月，P=0.09）。
减少脑转移死亡风险的独立因素包括：
体力状态评分<2
单纯脑转移
多学科治疗（MDT）
因此，该单中心大样本回顾研究结果表明，HER2阳性乳腺癌初诊时已发生脑转移的比例最高，其次为三阴性乳腺癌。初诊晚期乳腺癌时，可首先考虑对HER2阳性乳腺癌患者进行脑部筛查，故有必要进一步开展多中心前瞻随机对照研究。体力状态评分较低、单纯脑转移、接受多学科治疗的患者生存结局较好。对于HER2阳性乳腺癌，一线酪氨酸激酶抑制剂（拉帕替尼、吡咯替尼）与曲妥珠单抗治疗方案相比，中位总生存时间较长，尽管差异无统计学意义。
Breast. 2021 Feb 1;55:30-36.
Incidence, Risk factors and Survival of Patients with Brain Metastases at Initial Metastatic Breast Cancer Diagnosis in China.
Li Y, Li Q, Mo H, Guan X, Lin S, Wang Z, Chen Y, Zhang Y, Zhang D, Chen S, Cai R, Wang J, Luo Y, Fan Y, Yuan P, Zhang P, Li Q, Ma F, Xu B.
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Tiantan Hospital, Capital Medical University, China; Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
HIGHLIGHTS
Large retrospective analysis focusing on patients with BM at initial MBC diagnosis.
HER2-positive subtype presented with the highest incidence of BM at initial MBC diagnosis.
Patients with brain metastases only and receiving multidisciplinary treatment have a superior OS.
Brain screening might be considered in HER2-positive patients with BM at MBC diagnosis.
PURPOSE: To characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China.
METHODS: The China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively.
RESULTS: Brain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40-4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02-3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52-6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment.
CONCLUSION: HER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.
KEYWORDS: Brain metastases; Metastatic breast cancer; Incidence; Survival
PMID: 33310633
DOI: 10.1016/j.breast.2020.11.021
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