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Machine learning to guide the use of adjuvant therapies for breast cancer

Abstract

Accurate prediction of the individualized survival benefit of adjuvant therapy is key to making informed therapeutic decisions for patients with early invasive breast cancer. Machine learning technologies can enable accurate prognostication of patient outcomes under different treatment options by modelling complex interactions between risk factors in a data-driven fashion. Here, we use an automated and interpretable machine learning algorithm to develop a breast cancer prognostication and treatment benefit prediction model—Adjutorium—using data from large-scale cohorts of nearly one million women captured in the national cancer registries of the United Kingdom and the United States. We trained and internally validated the Adjutorium model on 395,862 patients from the UK National Cancer Registration and Analysis Service (NCRAS), and then externally validated the model among 571,635 patients from the US Surveillance, Epidemiology, and End Results (SEER) programme. Adjutorium exhibited significantly improved accuracy compared to the major prognostic tool in current clinical use (PREDICT v2.1) in both internal and external validation. Importantly, our model substantially improved accuracy in specific subgroups known to be under-served by existing models. Adjutorium is currently implemented as a web-based decision support tool (https://vanderschaar-lab.com/adjutorium/) to aid decisions on adjuvant therapy in women with early breast cancer, and can be publicly accessed by patients and clinicians worldwide.

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Fig. 1: Schematic depiction of the AutoPrognosis framework.
Fig. 2: Illustration for the ML model underlying Adjutorium.
Fig. 3: Discriminative accuracy evaluated in sub-cohorts of patients stratified by diagnosis date.
Fig. 4: Comparison between therapeutic decisions informed by Adjutorium and PREDICT v2.1.

Data availability

The dataset used to derive and internally validate the model was obtained from the National Cancer Registration and Analysis Service. These data are held by Public Health England. Information on how to access the data is available at http://ncin.org.uk/collecting_and_using_data/data_access. The dataset used for external validation was obtained from the Surveillance, Epidemiology and End Results programme, which can be accessed at https://seer.cancer.gov/seertrack/data/request/.

Code availability

The code for the AutoPrognosis software is available at https://bitbucket.org/mvdschaar/mlforhealthlabpub.

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Acknowledgements

We thank E. Topol (Scripps Research Institute), D. Dodwell (Oxford University), M. Cullen (Stanford University) and S. Sammutt (Cambridge University) for their comments.

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Contributions

A.M.A., D.G., A.L.H., J.R. and M.v.d.S. designed the study. A.M.A. and M.v.d.S. led the development of the automated ML model. A.M.A., D.G., A.L.H. and M.v.d.S. led the writing. D.G., A.L.H., J.R. and M.v.d.S. led the analysis and interpretation of the data. A.M.A. and D.G. provided statistical and analytical support. All authors read and approved the final draft of the manuscript. All authors are accountable for all aspects of the work.

Corresponding author

Correspondence to Mihaela van der Schaar.

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The authors declare no competing interests.

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Peer review informationNature Machine Intelligence thanks Morteza Noshad and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Alaa, A.M., Gurdasani, D., Harris, A.L. et al. Machine learning to guide the use of adjuvant therapies for breast cancer. Nat Mach Intell 3, 716–726 (2021). https://doi.org/10.1038/s42256-021-00353-8

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