Abstract
<div>AbstractPurpose:<p>We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor–positive advanced breast cancer tumors harboring an <i>ERBB2</i> mutation in the absence of a HER2 amplification.</p>Experimental Design:<p>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, <i>ERBB2</i>-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases <i>ERBB2</i> wild type.</p>Results:<p>A total of 45 <i>ERBB2</i>-mutant cases were identified for 90 matched controls. The presence of an <i>ERBB2</i> 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 <i>ERBB2</i>-mutated group. <i>ERBB2</i> mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with <i>ERBB2</i> wild type. In the co-mutational analyses, <i>CDH1</i> mutation was more frequent in the <i>ERBB2-</i>mutated group (FDR < 1). Although not significant, fewer co-occurring <i>ESR1</i> mutations and more <i>KRAS</i> mutations were identified in the <i>ERBB2</i>-mutated group.</p>Conclusions:<p><i>ERBB2</i>-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 (<i>CDH1</i>, <i>ESR1</i>, and <i>KRAS</i>) were noted between the <i>ERBB2</i>-mutated and the control group.</p></div>
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