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Association of breast cancer in men with exposure to 5-α reductase inhibitors: A RADAR report.
Developmental Therapeutics - Clinical Pharmacology and Immunotherapy
Session Type and Session Title:
Poster Discussion Session, Developmental Therapeutics - Clinical Pharmacology and Immunotherapy
J Clin Oncol 30, 2012 (suppl; abstr 2532)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
|No 5-αRI exposure||576||1,319,183||1,319,759||0.436|
|Attributable risk per
|Number needed to harm||564|
|p value||p < 0.00001|