Adverse Drug Event-based Stratification of Tumor Mutations

A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors

Chen Wang, Michael T. Zimmermann, Naresh Prodduturi, Christopher G. Chute, Guoqian D Jiang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Adverse drug events (ADEs) are a critical factor for selecting cancer therapy options. The underlying molecular mechanisms of ADEs associated with cancer therapy drugs may overlap with their antineoplastic mechanisms; an aspect of toxicity. In the present study, we develop a novel knowledge-driven approach that provides an ADE-based stratification (ADEStrata) of tumor mutations. We demonstrate clinical utility of the ADEStrata approach through performing a case study of breast invasive carcinoma (BRCA) patients receiving aromatase inhibitors (AI) from The Cancer Genome Atlas (TCGA) (n=212), focusing on the musculoskeletal adverse events (MS-AEs). We prioritized somatic variants in a manner that is guided by MS-AEs codified as 6 Human Phenotype Ontology (HPO) terms. Pathway enrichment and hierarchical clustering of prioritized variants reveals clusters associated with overall survival. We demonstrated that the prediction of per-patient ADE propensity simultaneously identifies high-risk patients experiencing poor outcomes. In conclusion, the ADEStrata approach could produce clinically and biologically meaningful tumor subtypes that are potentially predictive of the drug response to the cancer therapy drugs.

Original languageEnglish (US)
Pages (from-to)1160-1169
Number of pages10
JournalAMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium
Volume2014
StatePublished - 2014

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Aromatase Inhibitors
Drug-Related Side Effects and Adverse Reactions
Breast Neoplasms
Mutation
Neoplasms
Second Primary Neoplasms
Atlases
Pharmaceutical Preparations
Antineoplastic Agents
Cluster Analysis
Genome
Phenotype
Drug Therapy
Survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Adverse Drug Event-based Stratification of Tumor Mutations : A Case Study of Breast Cancer Patients Receiving Aromatase Inhibitors. / Wang, Chen; Zimmermann, Michael T.; Prodduturi, Naresh; Chute, Christopher G.; Jiang, Guoqian D.

In: AMIA ... Annual Symposium proceedings / AMIA Symposium. AMIA Symposium, Vol. 2014, 2014, p. 1160-1169.

Research output: Contribution to journalArticle

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