title: Exemestane Use in Postmenopausal Women at High Risk for Invasive Breast Cancer: Evaluating Biomarkers of Efficacy and Safety.
abstract: This phase II trial evaluated clinical markers of efficacy and safety of exemestane in postmenopausal women at increased risk for breast cancer. Postmenopausal women (n = 42) at risk for invasive breast cancer received 25 mg exemestane daily for 2 years along with calcium and vitamin D. The primary outcome was change in mammographic density (MD) after one year. Secondary outcomes included change in serum steroid hormones as well as change in trefoil protein 1 (TFF1) and proliferating cell nuclear antigen (PCNA) in breast tissue. Safety and tolerability were also assessed. MD decreased at 1 year and was significant at 2 years [mean change = -4.1%; 95% confidence intervals (CI), -7.2 to -1.1; P = 0.009]. Serum estradiol and testosterone levels significantly decreased at 3 months and remained suppressed at 12 months. After 1 year of treatment, TFF1 intensity decreased (mean change -1.32; 95% CI, -1.87 to -0.76; P < 0.001). Exemestane was safe and well tolerated. Exemestane decreased MD and expression of breast tissue TFF1. It was well tolerated with few clinically relevant side effects. MD and breast tissue TFF1 are potential biomarkers of breast cancer-preventive effects of exemestane in high-risk postmenopausal women.
authors.affiliation: Department of Medicine, Medstar Georgetown University Hospital, Washington, DC. Margaret.gatti@gmail.com.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Gatti-Mays
authors.affiliation: Biostatistics and Data Management Section, NCI, NIH, Bethesda, Maryland.
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.affiliation: Department of Radiology, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Galbo
authors.affiliation: Department of Medicine, Medstar Georgetown University Hospital, Washington, DC.
authors.forename: Andrea
authors.initials: A
authors.lastname: Singer
authors.affiliation: Department of Nuclear Medicine, NIH, Bethesda, Maryland.
authors.forename: James
authors.initials: J
authors.lastname: Reynolds
authors.affiliation: Division of Neuroradiology and Breast Imaging, Department of Radiology, Medstar Georgetown University Hospital, Washington, DC.
authors.forename: Erini
authors.initials: E
authors.lastname: Makariou
authors.affiliation: Department of Laboratory Medicine, Medstar Georgetown University Hospital, Washington DC.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kallakury
authors.affiliation: Division of Cancer Prevention, NCI, Rockville, Maryland.
authors.forename: Brandy M
authors.initials: BM
authors.lastname: Heckman-Stoddard
authors.affiliation: Division of Oncology, University of Washington, Seattle, Washington.
authors.forename: Larissa
authors.initials: L
authors.lastname: Korde
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC.
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC.
authors.forename: Robert
authors.initials: R
authors.lastname: Warren
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC.
authors.forename: Ann
authors.initials: A
authors.lastname: Gallagher
authors.affiliation: Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Eng-Wong
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015519:Bone Density / Q000187:drug effects; D000071060:Breast Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008055:Lipids / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D017698:Postmenopause; D011379:Prognosis; D011788:Quality of Life; D012307:Risk Factors
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D008055:Lipids; C056516:exemestane