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Gene expression signatures, clinicopathological features, and individualized therapy in breast cancer
JAMA, 04/03/08

Acharya CR et al. - Incorporation of gene expression signatures into clinical risk stratification can refine prognosis

• Retrospective study of early stage breast carcinoma candidates for adjuvant chemotherapy
• Review of microarray data for 964 clinically annotated breast tumor samples (573 in initial set; 391 in validation cohort)
• Relapse risk scores based on respective clinicopathologic features
• Main outcome measures: gene expression signatures and clinicopathological variables in early stage breast cancer to determine a refined estimation of relapse-free survival and sensitivity to chemotherapy

• In initial 573 pts, prognostically significant clusters as patterns of oncogenic pathway activation and tumor biology/microenvironment states were identified within the low-, intermediate-, and high-risk model cohorts
• Multivariate analyses confirmed independent prognostic value of genomic clusters
• Related, not identical, clusters in the independent validation cohort established reproducibility and validity of pathway deregulation patterns in predicting relapse risk
• The prognostic clinicogenomic clusters showed unique sensitivity patterns to commonly used cytotoxic therapies

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