BACKGROUND AND OBJECTIVE: Breast cancer gene expression signatures are developing rapidly and are expected to better understand the intrinsic features of the tumor, and also to optimize the treatment strategy in clinical practice. This review is to summarize the controversy and consensus in clinical practice of gene expression signatures, and to provide our perspective on these issues as well as recommendation for future direction. METHODS: We reviewed English publications in PubMed related to breast cancer gene expression signatures from 2002 to 2022. KEY CONTENT AND FINDINGS: Five mature commercial gene expression signatures: Oncotype, MammaPrint, Prosigna/PAM50, EndoPredict and Breast Cancer Index (BCI) are available to provide the prognostic and predictive assessment. Although they could help to evaluate the risk of recurrence and to predict the benefits of certain treatments, their applications remain challenging. Treatment decisions should be determined by a combination of related clinical pathological factors in clinical practice. CONCLUSIONS: Gene expression signatures could assist in the determination of the adjuvant therapy of early-stage breast cancer. The prospective randomized clinical trials showed that chemotherapy may be exempted in low-risk patients. More sufficient data are expected for the application in radiotherapy, extended endocrine therapy, and neoadjuvant treatment. The treatment cannot be determined by a single factor but by comprehensive assessments of clinicopathological factors, test purpose, and cost-effectiveness. Patients will benefit from personalized treatments with the publication of further evidence.