Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were 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, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median 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%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.
目的： 探讨抗人表皮生长因子受体2(HER-2)原发耐药与继发耐药对HER-2阳性晚期乳腺癌患者预后的影响。 方法： 选取1998—2018年于中国医学科学院肿瘤医院接受治疗的HER-2阳性晚期乳腺癌患者，分析其新辅助或辅助及晚期三线化疗的治疗情况。抗HER-2靶向治疗药物包括曲妥珠单抗、帕妥珠单抗、T-DM1、RC48-ADC、拉帕替尼、吡咯替尼、艾力替尼、西帕替尼、塞拉替尼。基于患者对抗HER-2治疗获益的持续时间，将患者分为原发抗HER-2耐药(原发耐药)组和继发抗HER-2耐药(继发耐药)组。以总生存时间(OS)为主要研究终点，生存分析采用Kaplan-Meier法。 结果： 全组284例患者发生复发转移时的中位年龄为48岁，激素受体阳性155例(54.6%)，阴性129例(45.4%)；绝经前128例(45.1%)，绝经后156例(54.9%)。初次确诊复发转移时美国东部肿瘤协作组(ECOG)功能状态(PS)评分0~1分277例(97.5%)，ECOG PS评分≥2分7例(2.5%)。原发耐药组103例(36.3%)，继发耐药组181例(63.7%)，两组患者中位OS分别为24.9和40.4个月，差异有统计学意义(P<0.001)。 结论： 抗HER-2原发耐药为HER-2阳性乳腺癌预后不良的因素之一，其机制有待进一步探索。.
Keywords: Acquired drug resistance; Anti-HER-2 drugs; Breast neoplasms; Primary drug resistance.