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Aromatase inhibitors and mammographic breast density in postmenopausal women receiving hormone therapy

Mousa, Noha A. MD1,5; Crystal, Pavel MD2; Wolfman, Wendy L. MD3; Bedaiwy, Mohamed A. MD4; Casper, Robert F. MD1,3,5

doi: 10.1097/gme.0b013e31816956c3

Objective: One of the main concerns regarding long-term use of hormone therapy (HT) in symptomatic menopausal women is the perceived increased risk of breast cancer. A method to reduce breast cancer risk in this population of women is urgently needed. We hypothesized that adding aromatase inhibitors (AIs) to HT would reduce local breast estrogen exposure and breast cancer risk without altering the beneficial systemic effects of HT on menopausal symptoms or bone density. The aim of this study was to investigate the effect of AIs and HT on mammographic breast density (MBD) as a surrogate marker of breast cancer risk in postmenopausal women receiving low-dose HT.

Design: This was a retrospective cohort study conducted at private clinics affiliated with a university hospital. One group of postmenopausal women (n = 28) received low-dose HT daily plus letrozole 2.5 mg three times weekly. Postmenopausal women receiving HT alone (n = 28) served as controls. MBD, the primary outcome, was measured using quantitative image analysis software as well as by visual analysis by a radiologist. Hypoestrogenic effects, adverse reactions, and bone mineral densities were secondary outcome measures.

Results: The mammograms of 18 women in the study group and 22 women in the control group were suitable for comparison. A statistically significant reduction in MBD occurred in the women who received HT plus an AI, whereas no significant change was observed in the women receiving HT alone. There was no significant increase in hypoestrogenic symptoms during the use of AIs, and bone mineral densities were not significantly reduced.

Conclusions: Adding an AI to HT may lower MBD in postmenopausal women. AIs could be good candidates for primary chemoprevention of breast cancer in postmenopausal women using HT.

This study investigated the effect of adding an aromatase inhibitor to current hormone therapy in healthy postmenopausal women at increased risk of breast cancer. A significant reduction in mammographic breast density was found, with no significant hypoestrogenic side effects, in the study group compared with a group of control women who received hormone therapy alone.

From the 1Institute of Medical Science, University of Toronto, Toronto, ON, Canada; 2Division of Breast Imaging, Department of Medical Imaging, Mount Sinai Hospital, Toronto, ON, Canada; 3Division of Reproductive Sciences, Fran and Lawrence Bloomberg Department of Obstetrics and Gynecology, Mount Sinai Hospital and University of Toronto, Toronto, ON, Canada; 4Reproductive Research Center, Cleveland Clinic, Cleveland, OH; and 5Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.

Received November 5, 2007; revised and accepted January 17, 2008.

Financial disclosure: Dr. Casper has patents for new hormone therapy regimens and licensing agreements with Ortho-McNeil, Barr Pharma, and Schering AG.

Address correspondence to: Robert F. Casper, MD, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Room 876, Toronto, ON, M5G 1X5, Canada. E-mail:

©2008The North American Menopause Society