1514 Background: Selective estrogen receptor modulators (SERMs) reduce the risk of breast cancer. Acceptance of SERMs is low due to toxicities. Agents with a better toxicity profile and surrogate endpoint biomarkers to evaluate the effect of preventive agents are needed. In addition to reducing the risk of recurrence of breast cancer, the aromatase inhibitors (AI) have been shown to reduce the risk of contralateral breast cancer in large phase III adjuvant studies. Our objective in this prospective short-term prevention study was to evaluate the effect of anastrozole on surrogate endpoint biomarkers in breast tissue and serum of women with breast cancer who are at increased risk for developing a contralateral second primary breast cancer. Methods: Women with a history of stage I, II breast cancer who were scheduled to start anastrozole for standard adjuvant treatment were eligible. After signing informed consent, patients underwent baseline fine needle aspiration (FNA) of the unaffected breast and serum collection for biomarker analysis before starting anastrozole at 1 mg per oral /day. A repeat FNA and serum collection were performed after 6 months of therapy. Biomarker endpoints included changes in ER and KI-67 expression in breast tissue analyzed by immunohistochemistry and insulin-like growth factor binding protein (IGFBP-1) in serum analyzed by ELISA. The difference in biomarkers before and after treatment was assessed using a Wilcoxon signed-rank test. Results: Forty two patients were enrolled and accrual has been completed. Median age was 58.8 (range 48–75). There was no change in ER or Ki-67 expression in pre- and posttreatment FNA samples. However, there was a statistically significant difference in pre- and posttreatment serum IGFBP-1 levels (p = 0.014); with pre-and post- mean treatment levels being 9.2 ng/mL and 13.5 ng/mL, respectively. Conclusions: We found a significant modulation of IGFBP-1 levels with 6 months of anastrozole treatment in women at increased risk of developing contralateral breast cancer. Anastrozole is currently being studied as a prevention agent in a large phase III trial, and our results provide support for continued evaluation of IGFBP-1 as a surrogate endpoint biomarker in prospective breast chemoprevention studies. [Table: see text]
Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers