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A Systematic Evaluation of Multi-Gene Predictors for the Pathological Response of Breast Cancer Patients to Chemotherapy

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
7
Issue
11
Identifiers
DOI: 10.1371/journal.pone.0049529
Keywords
  • Research Article
  • Biology
  • Biotechnology
  • Pharmacogenomics
  • Medicine
  • Diagnostic Medicine
  • Pathology
  • General Pathology
  • Biomarkers
  • Obstetrics And Gynecology
  • Breast Cancer
  • Oncology
  • Cancer Treatment
  • Chemotherapy And Drug Treatment
  • Oncology Agents
Disciplines
  • Biology
  • Medicine

Abstract

Previous studies have reported conflicting assessments of the ability of cell line-derived multi-gene predictors (MGPs) to forecast patient clinical outcomes in cancer patients, thereby warranting an investigation into their suitability for this task. Here, 42 breast cancer cell lines were evaluated by chemoresponse tests after treatment with either TFAC or FEC, two widely used standard combination chemotherapies for breast cancer. We used two different training cell line sets and two independent prediction methods, superPC and COXEN, to develop cell line-based MGPs, which were then validated in five patient cohorts treated with these chemotherapies. This evaluation yielded high prediction performances by these MGPs, regardless of the training set, chemotherapy, or prediction method. The MGPs were also able to predict patient clinical outcomes for the subgroup of estrogen receptor (ER)-negative patients, which has proven difficult in the past. These results demonstrated a potential of using an in vitro-based chemoresponse data as a model system in creating MGPs for stratifying patients’ therapeutic responses. Clinical utility and applications of these MGPs will need to be carefully examined with relevant clinical outcome measurements and constraints in practical use.

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