Decoding prognosis: multigene expression assays in breast cancer

Breast cancer remains a leading cause of cancer-related death in women worldwide. In early-stage, hormone receptor-positive/-negative disease, tissue-based multigene expression assays refine prognosis and guide systemic therapy. Axillary nodal status is still determined by clinical examination, imaging and sentinel lymph node biopsy (SLNB).

This narrative review separates prognostic, predictive and nodal-staging information. For MammaPrint, Oncotype DX, PAM50/Prosigna, EndoPredict and Breast Cancer Index, it summarizes the platform, validated population, level of evidence and guideline status. These assays estimate distant-recurrence risk and/or benefit from chemotherapy or extended endocrine therapy; none was developed or validated to predict nodal involvement. The dedicated gene-expression panels for nodal metastasis derive from retrospective or single-cohort studies, lack prospective validation and are not recommended for axillary staging. Liquid biopsy (ctDNA), multi-omics approaches, and cost, access and standardization are also reviewed.

The established assays answer narrow, population-specific answers on recurrence and systemic-treatment benefit, not axillary staging; omission of SLNB currently rests on clinical and radiological criteria (SOUND, INSEMA). Nodal signatures remain investigational, and ctDNA and multi-omics approaches are promising but not yet practice-changing, requiring prospective trials showing improved outcomes. Age- and menopausal-status-related chemotherapy effects derive largely from exploratory or subgroup analyses and are hypothesis-generating.