LeNoue-Newton Michele L, Chen Sheau-Chiann, Stricker Thomas, Hyman David M, Blauvelt Natalie, Bedard Philippe L, Meric-Bernstam Funda, Punglia Rinaa S, Schrag Deborah, Lepisto Eva M, Andre Fabrice, Smyth Lillian, Dogan Semih, Yu Celeste, Wathoo Chetna, Levy Mia, Eli Lisa D, Xu Feng, Mann Grace, Lalani Alshad S, Ye Fei, Micheel Christine M, Arnedos Monica
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
Clin Cancer Res. 2022 May 13;28(10):2118-2130. doi: 10.1158/1078-0432.CCR-21-0885.
We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor-positive advanced breast cancer tumors harboring an ERBB2 mutation in the absence of a HER2 amplification.
We retrospectively collected information from the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange registry database from patients with hormone receptor-positive, HER2-negative, ERBB2-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases ERBB2 wild type.
A total of 45 ERBB2-mutant cases were identified for 90 matched controls. The presence of an ERBB2 mutation was not associated with worse outcome determined by overall survival (OS) from first metastatic relapse. No significant differences were observed in phenotypic characteristics apart from higher lobular infiltrating subtype in the ERBB2-mutated group. ERBB2 mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with ERBB2 wild type. In the co-mutational analyses, CDH1 mutation was more frequent in the ERBB2-mutated group (FDR < 1). Although not significant, fewer co-occurring ESR1 mutations and more KRAS mutations were identified in the ERBB2-mutated group.
ERBB2-activating mutation was not associated with a worse OS from time of first metastatic relapse, or differences in TTP on treatment as compared with a series of matched controls. Although not significant, differences in coexisting mutations (CDH1, ESR1, and KRAS) were noted between the ERBB2-mutated and the control group.
我们想要确定在无HER2扩增情况下携带ERBB2突变的激素受体阳性晚期乳腺癌肿瘤的预后及表型特征。
我们回顾性地从美国癌症研究协会-基因组证据肿瘤信息交换登记数据库中收集了激素受体阳性、HER2阴性、ERBB2突变的晚期乳腺癌患者的信息。将表型和共突变特征以及治疗反应和结果与匹配的ERBB2野生型对照病例进行比较。
共鉴定出45例ERBB2突变病例以及90例匹配对照。从首次转移性复发开始计算的总生存期（OS）显示，ERBB2突变的存在与较差的预后无关。除了ERBB2突变组中较高的小叶浸润亚型外，在表型特征上未观察到显著差异。与ERBB2野生型相比，ERBB2突变似乎对内分泌治疗的反应或进展时间（TTP）没有影响。在共突变分析中，ERBB2突变组中CDH1突变更为频繁（错误发现率<1）。虽然不显著，但在ERBB2突变组中发现同时发生的ESR1突变较少，而KRAS突变较多。
与一系列匹配对照相比，ERBB2激活突变与首次转移性复发后的较差总生存期或治疗时的进展时间差异无关。虽然不显著，但在ERBB2突变组和对照组之间注意到共存突变（CDH1、ESR1和KRAS）存在差异。
