人表皮生长因子受体 ２ 阳性晚期乳腺癌靶向治疗耐药与预后关系的真实世界研究

Objective To explore the effect of primary and acquired resistance to anti-humanepidermal growth factor receptor 2 ( HER-2) on the overall survival of patients with HER-2 positive advancedbreast cancer. Methods The clinical characteristics of HER-2 positive patients with advanced breast canceradmitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018were collected, and their neoadjuvant / adjuvant and advanced three-line chemotherapy were summarized.Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib,pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, thepatients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2resistance group. In this study, the overall survival ( OS) was used as the main end point. Kaplan-Meieranalysis and Cox proportional risk regression model were used to analyze the effects of different drugresistance mechanisms on the overall survival. Results The whole group of 284 patients were included. Themedian age of recurrence and metastasis was 48 years old, 155 ( 54. 6%) were hormone receptor ( HR)positive and 129 ( 45. 4%) were HR negative, 128 cases ( 45. 1%) were premenopausal and 156 cases(54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases ( 2.5%)had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) inthe primary drug resistance group and 181 cases ( 63. 7%) in the secondary drug resistance group. Themedian overall survival time of the two groups was 24. 9 months and 40. 4 months, respectively, withstatistical significance (P<0.001). Conclusion Primary resistance to HER-2 is one of the factors of poorprognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.