Short -term biomarker modulation prevention study of Anastrozole in Women at increased risk for second primary breast cancer
Menée sur 37 patientes ayant eu un cancer du sein de stade I / II et présentant un risque élevé de récidive controlatérale, cette étude prospective évalue l'effet d'un traitement de courte durée à base d'anastrozole sur l'expression de biomarqueurs tumoraux dans le sérum et le tissu mammaire sain
The selective estrogen receptor modulators (SERMs), Tamoxifen and raloxifen reduce risk breast cancer. Patient acceptance is low due to toxicities. New agents with a better toxicity profile are needed. Aromatase inhibitors (AIs) reduce the risk of contralateral breast cancer and risk of new breast cancer in high risk women. However, the mechanism by which AIs reduce breast risk is not known. Surrogate biomarkers are needed to evaluate the effect of preventive agents. The objective of this prospective short-term prevention study was to evaluate the effect of anastrozole on biomarkers in breast tissue and serum of women at increased risk for developing a contralateral breast cancer. Women with a history of stage I, II breast cancer who started anastrozole for standard adjuvant treatment were eligible. 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 and again at 6 months. Biomarkers included changes in cytology, insulin like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), and IGFBP-3. Thirty-seven patients were enrolled. There was a significant modulation in serum IGFBP-1 levels between pre and post samples (p=0.02). No change was observed in IGF-1, IGFBP-3. and breast cytology. We showed a significant modulation of IGFBP-1 levels with 6 months anastrozole. 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.
Cancer Prevention Research , résumé, 2011