A BMI ≥ 25 kg/m2 in patients ≥ 50 years with ER+ tumors was weakly associated with a shorter breast cancer-free interval in tamoxifen-treated (Log-Rank p = 0.032; adjHR 1.72; 95% CI 1.00–2.95) and AI-treated patients (Log-Rank p = 0.055; adjHR 1.71; 95% CI 0.91–3.20) compared to patients with a lower BMI. This evidence concerns the gene ESR1 and breast cancer.