Cancer Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
BMC Cancer. 2024 Sep 30;24(1):1216. doi: 10.1186/s12885-024-12974-4.
Different hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear.
This retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi'an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method.
In total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39-0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46-0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P < 0.001; hazard ratio, 0.33; 95% CI, 0.18-0.59) and progression-free survival (PFS) (P < 0.001; hazard ratio, 0.38; 95% CI, 0.25-0.58) compared with not receiving endocrine therapy. Moreover, maintenance endocrine therapy after HER2-targeted therapy and chemotherapy is associated with significant advanced-OS and PFS benefits compared with no maintenance endocrine therapy (advanced-OS: P < 0.001; hazard ratio, 0.05; 95% CI, 0.03-0.12; PFS: P < 0.001; hazard ratio, 0.35; 95% CI, 0.21-0.57).
This study reveals the high heterogeneity of HER2-positive breast cancer related to HR status in clinicopathological features, metastasis patterns, and outcomes. Large randomized controlled trials are warranted to optimize treatment strategies for the HER2-positive breast cancer population.
不同的激素受体(HR)表达模式在人表皮生长因子受体 2(HER2)阳性乳腺癌患者中有重要的生物学和治疗意义。然而,HR 阳性/HER2 阳性(HR+/HER2+)和 HR 阴性/HER2 阳性(HR-/HER2+)亚型之间的区别仍不清楚。
本回顾性研究分析了 2012 年至 2022 年西安交通大学第一附属医院 828 例 HER2 阳性乳腺癌患者。采用卡方检验比较基线特征。采用 Kaplan-Meier 法估计生存结局。
总共,56.3%(n=466)有 HR 阳性,43.7%(n=362)有 HR 阴性疾病。相比之下,HR+/HER2+乳腺癌表现出较好的临床病理特征。中位随访 49 个月时,观察到 199 例无疾病生存(DFS)事件和 99 例死亡。HR+/HER2+患者的生存结局明显优于 HR-/HER2+患者。HR 阳性状态是总生存(OS)的独立保护因素[P=0.032;风险比,0.61;95%置信区间(CI),0.39-0.96]和 DFS(P=0.001;风险比,0.61;95%CI,0.46-0.81)。与 HR-/HER2+患者相比,HR+/HER2+患者对新辅助治疗的敏感性显著降低。在 HR+/HER2+晚期乳腺癌的一线治疗中,接受内分泌治疗显著改善了晚期 OS(P<0.001;风险比,0.33;95%CI,0.18-0.59)和无进展生存(PFS)(P<0.001;风险比,0.38;95%CI,0.25-0.58)。与未接受内分泌治疗相比,HER2 靶向治疗和化疗后进行维持内分泌治疗与显著的晚期 OS 和 PFS 获益相关(晚期 OS:P<0.001;风险比,0.05;95%CI,0.03-0.12;PFS:P<0.001;风险比,0.35;95%CI,0.21-0.57)。
本研究揭示了与 HR 状态相关的 HER2 阳性乳腺癌在临床病理特征、转移模式和结局方面存在高度异质性。需要进行大型随机对照试验来优化 HER2 阳性乳腺癌人群的治疗策略。