When patients with ER+ breast cancer relapse, up to 15% have lost ER expression and therefore targeting ER in this population is likely to be ineffective, although false negative ER results are a concern if the ER analysis was conducted on bone biopsies exposed to acid formalin, or if the analysis was conducted on samples prone to degradation such as cells detected in pleural fluid. Here, ESR1 is linked to breast carcinoma.