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Multi-omic machine learning predictor of breast cancer therapy response
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(2022) Multi-omic machine learning predictor of breast cancer therapy response. Nature, 601 . pp. 623-629. doi:10.1038/s41586-021-04278-5 ISSN 0028-0836.
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Official URL: https://doi.org/10.1038/s41586-021-04278-5
Abstract
Breast cancers are complex ecosystems of malignant cells and tumour microenvironment1. The composition of these tumour ecosystems and interactions within them contribute to cytotoxic therapy response2. Efforts to build response predictors have not incorporated this knowledge. We collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumours from 168 patients treated with chemotherapy +/- HER2-targeted therapy prior to surgery. Pathology endpoints (complete response or residual disease) at surgery3 were then correlated with multi-omic features in these diagnostic biopsies. Here we show that response to treatment is modulated by the pre-treated tumour ecosystem, and its multi-omics landscape can be integrated in predictive models using machine learning. The degree of residual disease following therapy is monotonically associated with pre-therapy features, including tumour mutational and copy number landscapes, tumour proliferation, immune infiltration and T-cell dysfunction and exclusion. Combining these features into a multi-omic machine learning model predicted pathological complete response in an external validation cohort (75 patients) with an AUC of 0.87. In conclusion, response to therapy is determined by the baseline characteristics of the totality of the tumour ecosystem captured through data integration and machine learning. This approach could be used to develop predictors for other cancers.
Item Type: | Journal Article | |||||||||||||||||||||||||||||||||||||||||||||
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Subjects: | Q Science > Q Science (General) R Medicine > RC Internal medicine |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Clinical Trials Unit Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Breast -- Cancer -- Treatment, Breast -- Cancer -- Chemotherapy, Machine learning | |||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nature | |||||||||||||||||||||||||||||||||||||||||||||
Publisher: | Nature Publishing | |||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 0028-0836 | |||||||||||||||||||||||||||||||||||||||||||||
Official Date: | 27 January 2022 | |||||||||||||||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 601 | |||||||||||||||||||||||||||||||||||||||||||||
Page Range: | pp. 623-629 | |||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41586-021-04278-5 | |||||||||||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 25 November 2021 | |||||||||||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 24 February 2022 | |||||||||||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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