We constructed a case–cohort design based on a random sample (n = 679) of all patients operated on for a first primary, non-metastatic, ER-positive, HER2-negative BC at the European Institute of Oncology (IEO) Milan, Italy during 1998–2002 and all additional patients (n = 303) operated during the same period, who developed an event (metastasis in distant organs or death due to BC as primary event) and were not included in the previous subset. Here, ESR1 is linked to breast cancer.