Multigene prognostic tests in breast cancer: past, present, future

Area of Science:

• Oncology
• Genomics
• Biomarker Discovery

Background:

• Multigene prognostic tests complement tumor size and grade in ER-positive breast cancer.
• Current tests, relying on ER and proliferation genes, have limited prognostic value in ER-negative cancers.
• First-generation signatures predict early recurrence but struggle with late events, posing challenges for extended therapies.

Purpose of the Study:

• To evaluate the evolving role and limitations of multigene prognostic tests in breast cancer.
• To explore newer signatures with improved prognostic value for late recurrences.
• To identify emerging biomarkers for ER-negative cancers and treatment response.

Main Methods:

• Analysis of gene expression data for prognostic signatures.
• Comparison of first-generation and newer multigene tests.
• Review of emerging research in immune gene signatures and tumor heterogeneity markers.

Main Results:

• Newer tests (Prosigna, EndoPredict, Breast Cancer Index) demonstrate better prediction of late recurrences.
• No clinically useful prognostic signatures currently exist for ER-negative breast cancers.
• Immune gene signatures and tumor heterogeneity metrics show potential as independent prognostic and predictive markers.

Conclusions:

• Advancements in multigene tests are improving breast cancer prognosis, particularly for late recurrences.
• Further research is needed for ER-negative cancers and personalized treatment response prediction.
• High-throughput technologies offer opportunities for integrated multiplatform prediction models.