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Characteristics and Outcome of AKT1 E17K-Mutant Breast Cancer Defined through AACR Project GENIE, a Clinicogenomic Registry.


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 patients with matched AKT1 E17K-mutant (n = 153) and AKT1-wild-type (n = 302) metastatic breast cancer. AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wild-type 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. SIGNIFICANCE: We delineate the natural history of a rare genomically distinct cancer, AKT1 E17K-mutant ER-positive breast cancer, using a publicly accessible registry of real-world patient data, thereby illustrating the potential to inform drug registration through synthetic control data.See related commentary by Castellanos and Baxi, p. 490.

SUBMITTER: Smyth LM 

PROVIDER: S-EPMC7125034 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Characteristics and Outcome of <i>AKT1</i> <sup>E17K</sup>-Mutant Breast Cancer Defined through AACR Project GENIE, a Clinicogenomic Registry.

Smyth Lillian M LM   Zhou Qin Q   Nguyen Bastien B   Yu Celeste C   Lepisto Eva M EM   Arnedos Monica M   Hasset Michael J MJ   Lenoue-Newton Michele L ML   Blauvelt Natalie N   Dogan Semih S   Micheel Christine M CM   Wathoo Chetna C   Horlings Hugo H   Hudecek Jan J   Gross Benjamin E BE   Kundra Ritika R   Sweeney Shawn M SM   Gao JianJiong J   Schultz Nikolaus N   Zarski Andrew A   Gardos Stuart M SM   Lee Jocelyn J   Sheffler-Collins Seth S   Park Ben H BH   Sawyers Charles L CL   André Fabrice F   Levy Mia M   Meric-Bernstam Funda F   Bedard Philippe L PL   Iasonos Alexia A   Schrag Deborah D   Hyman David M DM  

Cancer discovery 20200110 4


AKT inhibitors have promising activity in <i>AKT1</i> <sup>E17K</sup>-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 patients with matched <i>AKT1</i> <sup>E17K</sup>-mutant (<i>n</i> = 153) and <i>AKT1</i>-wild-type (<i>n</i> = 302) metastatic breast cancer. <i>AK  ...[more]

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