Details

Autor(en) / Beteiligte

• WEITZEL, Jeffrey N
• BUYS, Saundra S
• SHERMAN, William H
• DANIELS, Anna Marie
• URSIN, Giske
• DANIELS, John R
• MACDONALD, Deborah J
• BLAZER, Kathleen R
• PIKE, Malcolm C
• SPICER, Darcy V

Titel

Reduced Mammographic Density with Use of a Gonadotropin-Releasing Hormone Agonist–Based Chemoprevention Regimen in BRCA1 Carriers

Ist Teil von

• Clinical cancer research, 2007-01, Vol.13 (2), p.654-658

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Purpose: Women with a BRCA1 mutation ( BRCA1 mut ) need risk reduction options beyond mastectomy and oophorectomy. We evaluated the efficacy, safety, and tolerability of hormonal chemoprevention with a gonadotropin-releasing hormone agonist (GnRHA) with low-dose add-back steroids in BRCA1 mut carriers. Experimental Design : The 12-month open label clinical trial used the GnRHA deslorelin, ultra-low-dose estradiol (E 2 ), and replacement testosterone, administered via daily intranasal spray in premenopausal women with a BRCA1 mut , and intermittent oral medroxyprogesterone acetate. The end points included mammographic percent density, bone mineral density, endometrial hyperplasia, symptom inventory, and quality of life (Medical Outcomes SF-36 survey). Results: Six of eight BRCA1 mut women (mean age, 30.3 years; range, 25-36 years) completed the study. Mammographic percent density was significantly reduced at 12 months (median absolute mammographic percent density decrease, 8.3%; P = 0.043), representing a 29.2% median reduction in mammographic percent density. Bone mineral density remained within reference limits for all participants; there were no cases of atypical endometrial hyperplasia and menses resumed within a median of 67 days (range, 35-110 days) after last drug treatment day. The treatment was well tolerated; hypoestrogenic side effects were minimal and transient; and there were no significant changes in quality of life. Conclusions: The GnRHA deslorelin, with low-dose add-back steroids, was well tolerated and significantly decreased mammographic percent density in BRCA1 mut carriers. This regimen may reduce breast cancer risk and improve the usefulness of mammographic surveillance by reducing density. This is the first demonstration, to our knowledge, of a direct reduction of mammographic densities in young BRCA1 mut carriers.