title: Short-term biomarker modulation prevention study of anastrozole in women at increased risk for second primary breast cancer.
abstract: The selective estrogen receptor modulators (SERM), Tamoxifen and raloxifen reduce risk breast cancer. Patient acceptance of SERMs for breast cancer prevention is low due to toxicities. New agents with a better toxicity profile are needed. Aromatase inhibitors (AI) 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 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 postsamples (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 six 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.
authors.affiliation: Department of Breast Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. barun@mdanderson.org
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Diane
authors.initials: D
authors.lastname: Liu
authors.forename: Abenaa
authors.initials: A
authors.lastname: Brewster
authors.forename: Marjorie
authors.initials: M
authors.lastname: Green
authors.forename: Angelica
authors.initials: A
authors.lastname: Gutierrez-Barrera
authors.forename: Ugur
authors.initials: U
authors.lastname: Akar
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
mesh_terms: D000368:Aged; D000077384:Anastrozole; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000188:drug therapy*; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000097:blood / Q000175:diagnosis* / Q000517:prevention & control; D009570:Nitriles / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D007334:Insulin-Like Growth Factor I; D004247:DNA; D001141:Aromatase