96571-114

Association of breast cancer in men with exposure to 5-α reductase inhibitors: A RADAR report.

Subcategory: 
Category: 
Developmental Therapeutics - Clinical Pharmacology and Immunotherapy
Session Type and Session Title: 
Poster Discussion Session, Developmental Therapeutics - Clinical Pharmacology and Immunotherapy
Abstract Number: 

2532

Citation: 

J Clin Oncol 30, 2012 (suppl; abstr 2532)

Author(s): 

Steven M Belknap, Victoria Godinez-Puig, Robert E Brannigan, Simon M Lin, John Cashy, Rajesh Chowdhary, Michael J Postelnick, Michael A Fotis, Michael Irwig, Seema Ahsan Khan, William John Gradishar, Vishvas Garg, Xian Shen, Dennis W Raisch, Beatrice Nardone, Steven T. Rosen, Beatrice J. Edwards, June M McKoy, Paul R Yarnold, Dennis P. West; Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Dermatology, Northwestern University, Chicago, IL; Department of Urology, Nortwestern University Feinberg School of Medicine, Chicago, IL; Biomedical Informatics Research Center, Marshfield Clinic Research Foundation, Marshfield, WI; Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL; Department of Family and Community Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Endocrinology, Medical Faculty Associates, George Washington University, Washington, DC; Robert H. Lurie Comprehensive Cancer Center of Northwestern University Feinberg School of Medicine, Chicago, IL; Maggie Daley Center for Women's Cancer Care, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; College of Pharmacy, University of New Mexico, Albuquerque, NM; VA Center for Cooperative Pharmaceutical Studies, University of New Mexico, Albuquerque, NM; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Department of Orthopedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL; Robert H. Lurie Comprehensive Cancer Center and Department of Medicine, Division of General Internal Medicine and Geriatrics, Northwestern University Feinberg School of Medicine, Chicago, IL; Optimal Data Analysis, Inc, San Diego, CA


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Breast cancers in men (BCM) account for <1% of all breast cancers. Dihydrotestosterone (DHT) inhibits proliferation of normal and neoplastic mammary tissue and constrains the effect of estrogens. Finasteride (F) and dutasteride (D) are 5-α reductase inhibitors (5-αRIs) that reduce systemic and local dihydrotestosterone and cause gynecomastia in 1–3% of men. The package inserts for F and D state, “the relationship between long-term use of (finasteride/dutasteride) and male breast neoplasia is currently unknown.” F and D are marketed for treatment of symptomatic benign-prostatic hyperplasia. F is marketed for treatment of androgenetic alopecia. Methods: To detect disproportionality in the FDA MedWatch dataset, we calculated the empiric Bayes geometric mean (EBGM) for association of BCM with F or D. We also calculated the attributable risk of BCM exposed to F or D among men at an urban academic hospital (Northwestern Memorial Hospital) and at a rural healthcare system (Marshfield Clinic). Results: In the MedWatch dataset, we identified 33 reports of F-associated BCM and 5 reports of D-associated BCM. For F–associated BCM, the EBGM was 58.95 (95% CI 24.47-81.76; p=0.0001). For D-associated BCM, the EBGM was 15.79 (95% CI 4.57-35.49; p=0.0001). The mean age for BCM after 5-αRI exposure was 70±11 years; 11/38 (29%) had gynecomastia. There were 38 cases of BCM associated with 5-αRI in the combined Northwestern and Marshfield cohort (see table below). Conclusions: We found a highly significant association between BCM and 5-αRI exposure in each of 6 separate analyses (3 sources X 2 drugs), with an estimated 1 extra BCM per 564 men exposed to 5-αRIs. We now plan to assess BRCA status and other risk factors. Given that 5-αRIs are marketed for control of lower urinary tract symptoms or for cosmetic purposes, it is not immediately obvious that use of finasteride or dutasteride for their labeled indications would provide any net benefit.
Risk of breast cancer in men with 5-αRI exposure.
Breast cancer
Total Risk/
1,000
Yes No
5-αRI exposure 38 17,161 17,199 2.21
No 5-αRI exposure 576 1,319,183 1,319,759 0.436
Total 614 1,336,344 1,336,958
95% CI
Attributable risk per
1,000 men
1.77 (1.07–2.48)
Risk ratio 5.1 (3.6–7.0)
Number needed to harm 564
Chi-square 116.3
p value p < 0.00001