This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weitzel, J. N. Articles by Spicer, D. V. Search for Related Content PubMed PubMed Citation Articles by Weitzel, J. N. Articles by Spicer, D. V. Related Collections Clinical Intervention Clinical Intervention:Molecular Targeted Drugs

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

Authors' Affiliations: ¹ Department of Clinical Cancer Genetics, City of Hope Cancer Center, Duarte, California; Departments of ² Preventive Medicine, and ³ Medicine, USC/Norris Cancer Center, University of Southern California, Los Angeles, California; ⁴ Department of Medicine, Huntsman Cancer Institute at the University of Utah, Salt Lake City, Utah; ⁵ Herbert Irving Cancer Center, New York Presbyterian Hospital, New York, New York; ⁶ Balance Pharmaceuticals, Inc., Santa Monica, California; and ⁷ Department of Nutrition, University of Oslo, Oslo, Norway

Requests for reprints: Jeffrey N. Weitzel, City of Hope Cancer Center, 1500 East Duarte Road, Duarte, CA 91010. Phone: 626-256-8662, ext. 2; Fax: 626-930-5495; E-mail: jweitzel{at}coh.org.

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 (E₂), 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.

This article has been cited by other articles:

				J. J. Heine, M. J. Carston, C. G. Scott, K. R. Brandt, F.-F. Wu, V. S. Pankratz, T. A. Sellers, and C. M. Vachon An Automated Approach for Estimation of Breast Density Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 3090 - 3097. [Abstract] [Full Text] [PDF]

				D. B. Kopans Basic Physics and Doubts about Relationship between Mammographically Determined Tissue Density and Breast Cancer Risk Radiology, February 1, 2008; 246(2): 348 - 353. [Abstract] [Full Text] [PDF]