High young-adult body mass index (BMI) was inversely associated with postmenopausal breast cancer risk, regardless of hormone receptor status, whereas high current BMI and high adult weight gain were associated with two-fold increased risk of estrogen receptor and progesterone receptor positive breast cancer, but only in women with a low young-adult BMI (≤22.4 kg/m2) or those with ≥15 years since menopause. The gene discussed is ESR1; the disease is breast cancer.