Characteristics and Outcome of AKT1E17K-Mutant Breast Cancer Defined through AACR Project GENIE, a Clinicogenomic Registry
- 1 April 2020
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Discovery
- Vol. 10 (4), 526-535
- https://doi.org/10.1158/2159-8290.cd-19-1209
Abstract
AKT inhibitors have promising activity in AKT1E17K-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 AKT1E17K-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, AKT1E17K-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.Keywords
Other Versions
Funding Information
- AACR AstraZeneca
- NIH NCI Memorial Sloan-Kettering Cancer Center (P30 CA008748)
- The Sheikh Khalifa Bin Zayed Al Nahyan Institute
- Cancer Prevention and Research Institute of Texas (RP150535)
This publication has 22 references indexed in Scilit:
- AACR Project GENIE: Powering Precision Medicine through an International ConsortiumCancer Discovery, 2017
- AKT Inhibition in Solid Tumors With AKT1 MutationsJournal of Clinical Oncology, 2017
- Implementing Genome-Driven OncologyCell, 2017
- Genomic Characterization of Primary Invasive Lobular Breast CancerJournal of Clinical Oncology, 2016
- Correlative Analysis of Genetic Alterations and Everolimus Benefit in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From BOLERO-2Journal of Clinical Oncology, 2016
- Comprehensive molecular portraits of human breast tumoursNature, 2012
- Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics supportJournal of Biomedical Informatics, 2008
- Mutational analysis of oncogenic AKT E17K mutation in common solid cancers and acute leukaemiasBritish Journal of Cancer, 2008
- A transforming mutation in the pleckstrin homology domain of AKT1 in cancerNature, 2007
- Survival Analysis Techniques for Censored and Truncated DataTechnometrics, 1998