Division of Medical Oncology, Kuang Tien General Hospital Cancer Center, Taichung, Taiwan.
Department of Medical Research, MacKay Memorial Hospital, New Taipei, Taiwan.
Cancer Med. 2024 Jul;13(14):e70035. doi: 10.1002/cam4.70035.
The prognostic capability of targeted sequencing of primary tumors in patients with estrogen receptor-positive, human epidermal growth factor receptor-2-negative early-stage invasive breast cancer (EBC) in a real-world setting is uncertain. Therefore, we aimed to determine the correlation between a 22-gene mutational profile and long-term survival outcomes in patients with ER+/ERBB2- EBC.
A total of 73 women diagnosed with ER+/ERBB2- EBC between January 10, 2004, and June 2, 2008, were followed up until December 31, 2022. Univariate and multivariate Cox models were constructed to plot the relapse-free survival (RFS) and overall survival (OS). The log-rank test derived p-value was obtained. For external validation, we performed a survival analysis of 1163 comparable patients retrieved from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset.
At follow-up, 16 (21.9%) patients had relapsed, while 21 (nearly 29%) harbored mutant genes. Thirty-three missense mutations were detected in 14 genes. The median ages were 51 and 46 years in patients with and without mutations, respectively. Patients with any mutation had a 1.85-fold higher risk of relapse (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 0.60-5.69) compared to those without any mutation. Patients who harbored any of the six genes (MAP2K4, FGFR3, APC, KIT, RB1, and PTEN) had a nearly 6-fold increase in the risk of relapse (HR: 5.82, 95% CI: 1.31-18.56; p = 0.0069). Multivariate Cox models revealed that the adjusted HR for RFS and OS were 6.67 (95% CI: 1.32-27.57) and 8.31 (p = 0.0443), respectively. METABRIC analysis also demonstrated a trend to significantly worse RFS (p = 0.0576) in the subcohort grouped by having a mutation in any of the six genes.
Our single-institution tissue bank study of Taiwanese women with ER+/ERBB2- EBC suggests that a novel combination of six gene mutations might have prognostic capability for survival outcomes.
在真实环境中，针对雌激素受体阳性、人表皮生长因子受体 2 阴性早期浸润性乳腺癌（EBC）患者的原发肿瘤进行靶向测序的预后能力尚不确定。因此，我们旨在确定 22 基因突变谱与 ER+/ERBB2-EBC 患者长期生存结果之间的相关性。
共纳入 73 例 2004 年 1 月 10 日至 2008 年 6 月 2 日期间诊断为 ER+/ERBB2-EBC 的女性患者，随访至 2022 年 12 月 31 日。构建单因素和多因素 Cox 模型以绘制无复发生存（RFS）和总体生存（OS）曲线。通过对数秩检验获得 p 值。为了外部验证，我们对从分子乳腺癌国际联合会（METABRIC）数据集检索到的 1163 例可比患者进行了生存分析。
随访时，16 例（21.9%）患者复发，21 例（近 29%）患者存在突变基因。在 14 个基因中检测到 33 个错义突变。中位年龄分别为有突变和无突变患者的 51 岁和 46 岁。与无任何突变的患者相比，任何突变患者的复发风险增加 1.85 倍（风险比 [HR]：1.85，95%置信区间 [CI]：0.60-5.69）。携带任何 6 个基因（MAP2K4、FGFR3、APC、KIT、RB1 和 PTEN）之一的患者复发风险增加近 6 倍（HR：5.82，95%CI：1.31-18.56；p=0.0069）。多因素 Cox 模型显示，RFS 和 OS 的调整后 HR 分别为 6.67（95%CI：1.32-27.57）和 8.31（p=0.0443）。METABRIC 分析还表明，在根据任何 6 个基因之一的突变进行分组的亚组中，RFS 显著更差的趋势（p=0.0576）。
我们对台湾雌激素受体阳性、人表皮生长因子受体 2 阴性早期浸润性乳腺癌（EBC）患者的单机构组织库研究表明，六种基因突变的新组合可能对生存结果具有预后能力。
