In the meta-analysis of IHC-defined ER positive patients, whilst ESR1 based ER classification was not associated with significant higher risk of relapse (HR = 1.39, 95% CI: 0.86–2.23), 23-gene signature-based ER negative tumours within this cohort were correlated with a poorer distant-metastasis-free survival over 5 years relative to the ER positive tumours defined by both IHC and the 23-gene signature (HR = 1.98, 95% CI: 1.19–3.28) (Supplement figure S4). The gene discussed is ESR1; the disease is neoplasm.