Characteristics and outcome of AKT1 E17K-mutant breast cancer defined through AACR GENIE, a clinicogenomic registry.

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2020
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Abstract
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.
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smyth2020characteristicscancer Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Smyth, Lillian M;Zhou, Qin;Nguyen, Bastien;Yu, Celeste;Lepisto, Eva M;Arnedos, Monica;Hassett, Michael J;Lenoue-Newton, Michele L;Blauvelt, Natalie;Dogan, Semih;Micheel, Christine M;Wathoo, Chetna;Horlings, Hugo;Hudecek, Jan;Gross, Benjamin E;Kundra, Ritika;Sweeney, Shawn M;Gao, Jianjiong;Schultz, Nikolaus;Zarski, Andrew;Gardos, Stuart M;Lee, Jocelyn;Sheffler-Collins, Seth;Park, Ben H;Sawyers, Charles L;Andre, Fabrice;Levy, Mia;Meric-Bernstam, Funda;Bedard, Phillipe L;Iasonos, Alexia;Schrag, Deborah;Hyman, David M;Genie Consortium, Aacr Project;
Journal Cancer Discovery
Year 2020
DOI
CD-19-1209
URL
Keywords
Breast cancer immunotherapy immunotoxins scfv epha2 receptor pseudomonas exotoxin

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