AKT inhibitors have promising activity in AKT1 E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of matched AKT1 E17K-mutant (n=153) and -wildtype (n=302) metastatic breast cancer patients. AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wildtype controls (median OS, 24.1 vs 29.9, respectively; p=0.98). AKT1-mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology.

中文翻译：

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通过临床基因组学注册 AACR GENIE 定义的 AKT1 E17K 突变型乳腺癌的特征和结果。

AKT 抑制剂在 AKT1 E17K 突变雌激素受体 (ER) 阳性转移性乳腺癌中具有良好的活性，但这种罕见的基因组亚型的自然史仍然未知。利用国际临床基因组数据共享联盟 AACR Project GENIE，我们对匹配的 AKT1 E17K 突变体（n=153）和野生型（n=302）转移性乳腺癌患者的临床结果进行了比较分析。与 AKT1 野生型对照相比，AKT1 突变病例具有相似的调整后总生存期 (OS)（中位 OS，分别为 24.1 和 29.9；p=0.98）。AKT1 突变病例在 mTOR 抑制剂治疗中的持续时间更长，由于这种改变的罕见性，以前在关键临床试验中没有认识到这一观察结果。其他基线临床病理特征以及其他类别治疗的持续时间大致相似。