ESR1 and in situ carcinoma: Interestingly, patients staged with carcinoma in situ who underwent breast-conserving surgery had significantly higher incidences of second primary tumors compared with patients with stage T1 tumors (HR 1.19, P < 0.0001; and HR = 1.12, P = 0.0374 for ER-positive and ER-negative patients, respectively) (Fig. 2).