[Risk stratification assessment of brain metastasis in newly diagnosed non-stage IV breast cancer patients with HER-2-low expression following systemic therapy]

Objective: To explore the independent risk factors of brain metastasis after systematic treatment in newly diagnosed non-stage Ⅳ breast cancer patients with HER-2-low expression, and to determine the recurrence risk stratification of brain metastasis, so as to guide the follow-up pattern of patients with different risk stratification. Methods: A retrospective analysis was performed on non-stage Ⅳ breast cancer patients admitted to Shandong First Medical University Affiliated Tumor Hospital from January 2012 to January 2020 with complete follow-up data. According to the immunohistochemical test results, only HER-2-low breast cancer patients confirmed by postoperative pathology were enrolled. The independent risk factors and the rate of brain metastasis were analyzed, and brain metastasis risk stratification was performed based on the number of independent risk factors. Results: 247 patients were enrolled, with a median follow-up of 51 months, 138 patients developed brain metastasis during follow-up, and the median development time was 55.5 months. Univariate analysis showed that age, menopause status, ER, tissue grade, T stage, N stage, CEA, CA125 and CA153 were associated with brain metastasis (P＜0.05). Multivariate logistic regression analysis showed that negative ER (OR=2.486, 95% CI: 1.117-5.533), tissue gradeⅡ (OR=12.175, 95% CI: 2.991-49.567), tissue grade Ⅲ (OR=14.03, 95% CI: 3.383-58.184), T2 stage (OR=2.272, 95% CI: 1.122-4.602), T3 stage (OR=9.05, 95% CI: 1.804-45.398), T4 stage (OR=6.691, 95% CI: 1.814-24.676), number of axillary lymph node metastasis≥10, N3 (OR=2.748, 95% CI: 1.041-7.260), CA125 higher than the reference value (OR=3.933, 95% CI: 1.601-9.66) and CA153 higher than the reference value (OR=2.578, 95% CI: 1.161-5.724) were independent risk factors for brain metastasis (P＜0.05). The risk of brain metastasis was assessed according to the number of independent risk factors in patients: Those with 0 risk factor were classified as low-risk group, 1-2 risk factors as medium-risk group, 3-4 risk factors as high-risk group, and 5-6 risk factors as extremely high-risk group. The incidence of brain metastases in each group were 0 (0/3), 33.33% (39/117), 74.55% (82/110) and 100.00% (17/17), respectively. Conclusion: The risk stratification of brain metastasis based on clinicopathological characteristics and levels of related tumor markers are helpful to predict the risk of brain metastasis in non-stage Ⅳ breast cancer patients with HER-2 low expression after systematic treatment, so as to accurately identify patients with high recurrence risk and formulate targeted follow-up strategies for them.