Background: Anastrozole, an aromatase inhibitor, decreases estrogen synthesis and is therefore, an effective treatment of (HR) positive breast cancer. We hypothesized that a short course of anastrozole can decrease levels of Ki-67, a surrogate measure of chemoprevention (the primary endpoint), and there may be correlation in Ki-67 reduction and decreased size of tumor on MRI (the secondary endpoint). Methods: In a single group phase II trial, 42 postmenopausal women with HR positive DCIS or early invasive breast cancer following diagnostic biopsy were enrolled. Patients were given 1 mg anastrozole for 2-4 weeks. Patients had an MRI before and after anastrozole, and then underwent surgery for measurement of change in Ki-67. The specimens were histologically graded on Ki-67, estrogen receptor (ER), progesterone receptor (PR), and Nottingham grade to compare pre and post-therapeutic effects of anastrozole. The two-sided Wilcoxon signed-rank test and Fisher’s exact test were utilized to analyze the data. Spearman correlation coefficients were obtained to assess the correlation between Ki-67 and MRI. Results: 34 patients were eligible. 15 out of 23 patients (65.2%) had decreased Ki-67, 5 (21.7%) had no change and 3 (13.0%) had increased Ki-67 levels. On average, there was a significant decrease in Ki-67 level of 4.9 from baseline (95% CI 1.8, 8.0; p-value=0.004). There was a significant decrease in grade of 0.3 (0.10, 0.49; p-value=0.016). Out of 34 patients, 5 patients (14.7%) showed a pathological complete response. In terms of HR, on average, there was a significant decrease in PR of 34.5 (8.98, 60.2; p-value=0.021). However, there was no significant change in ER (p-value=0.96). Among the 12 patients who had both Ki-67 and tumor size data available, there was low correlation between the change of Ki-67 level from baseline and the change of tumor size determined by MRI (R=0. 34). Conclusions: Anastrozole, as preoperative therapy for 2-4 weeks was effective in reducing Ki-67 in early invasive HR positive breast cancer. Thus the study met its primary endpoint, and therefore supports chemo preventive effects of aromatase inhibitors as shown in large chemoprevention trials. Clinical trial information: NCT00256217.