1522 Background: The proportion of baseline weight or fat loss needed for breast cancer risk reduction in overweight women is not defined. We conducted a pilot study to determine the effect of a structured weight loss program on serum and tissue breast cancer risk biomarkers. Methods: Postmenopausal women with BMI > 25 kg/m2 not on HRT were eligible if they met risk criteria of 5-yr Gail > 1.7%, prior contra- lateral breast cancer, or precancerous biopsy; and had breast tissue harvested by random periareolar fine needle aspiration (RPFNA) indicating evidence of hyperplasia and Ki-67 > 1.5%. Our primary endpoint was to determine the proportion of women with ≥ 5% weight loss and effect on Ki-67. Due to low proportion of women with Ki-67, minimum eligibility criteria were changed to cytomorphology and a frozen aliquot. Our 6-month weight loss intervention included reduced energy diet, physical activity, and weekly meetings for behavioral strategies with other high risk women. Body composition (DEXA), fasting...