After integrating predictors of upstaging and factors associated with positive ALNs in this study, we found that patients with larger tumor size (>2 cm), multifocal lesions or ER+HER2+ status were more likely to be upstaging patients with positive ALNs, who might need axillary evaluation more than patients with relatively low risk of upstaging or axillary metastasis. The gene discussed is ESR1; the disease is neoplasm.