Menopause: The Journal of The North American Menopause Society Vol. 19, No. 4, pp. 000/000 DOI: 10.1097/gme.0b013e31823772a8 * 2011 by The North American Menopause Society The effect of acute aromatase inhibition on breast parenchymal enhancement in magnetic resonance imaging: a prospective pilot clinical trial Noha A. Mousa, MD, PhD, 1,2,3 Riham Eiada, MD, 4,5 Pavel Crystal, MD, 4,5 Dan Nayot, MD, 1 and Robert F. Casper, MD, FRCS(C) 1,2,6 Abstract Objective: The breast is highly hormonally sensitive especially to the sex steroid hormone estrogen. Both physiological and iatrogenic steroid hormone modifications could affect how the breast tissue may appear in breast imaging techniques. We hypothesized that estrogen deprivation therapy could reduce breast nonspecific enhance- ment on magnetic resonance imaging (MRI). Methods: This study was a prospective pilot phase II clinical trial. The study was approved by Health Canada and the institutional research ethics board, and participants signed informed consent forms. Sixteen healthy post- menopausal women were enrolled, and 14 completed the study. Baseline breast MRI was done followed 1 month later by administration of a high-dose aromatase inhibitor (letrozole 12.5 mg/day) for 3 successive days before a second breast MRI. Background breast parenchymal enhancement was compared between the pretreatment and posttreatment studies. Results: There was a statistically significant reduction of the average background breast enhancement after treatment with aromatase inhibitors compared with baseline MRI. Of particular interest, specific areas of benign breast enhancement were reduced after aromatase inhibitor treatment. No significant adverse effects were recorded using this relatively high dose of the aromatase inhibitors. Conclusions: This preliminary study provided evidence that aromatase inhibitors could reduce the parenchymal background enhancement of benign breast tissue during MRI and may improve the specificity of the technique. Key Words: Breast Y Magnetic resonance imaging Y Aromatase inhibitors Y Menopause Y Enhancement. B reast magnetic resonance imaging (MRI) is increas- ingly used in diagnosing and staging breast cancer (BC). 1 It is believed to be more sensitive than mam- mograms in detecting multiple cancerous foci, especially in women with dense breasts. 2 It is also more accurate in diag- nosing high-grade tumors 3 and has better sensitivity than mammograms and breast ultrasound in diagnosing BC in BRCA mutation carriers. 4,5 Mammograms seem to be inad- equate as a screening method for BRCA mutation carriers, despite being the standard screening modality at present. 6 The magnetic field of MRI, together with the variable magnetic fields of gradients and radiofrequency excitation, results in detailed cross-sectional images of the breast, which have very good soft tissue contrast. The contrast between breast tissue types such as between fat and glandular tissue or breast lesions is determined by the mobility and magnetic Received June 23, 2011; revised and accepted August 16, 2011. From the 1 Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; 2 Institute of Medical Science, Uni- versity of Toronto, Toronto, Ontario, Canada; 3 Department of Obstetrics and Gynecology, Assiut University, Asyut, Egypt; 4 Marvelle Koffler Breast Centre, Mount Sinai Hospital, Toronto, Toronto, Ontario, Canada; 5 Department of Radiology, University of Toronto, Toronto, Ontario, Canada; and 6 Samuel Lunenfeld Research Institute, Mount Sinai Hospi- tal, Toronto, Toronto, Ontario, Canada. Funding/support: The study was funded by the Canadian Foundation for Women’s Health (CFWH). N.A.M. is supported by the health professional and Bisby fellowships from the Canadian Institute of Health Research, and R.F.C. is supported by the Camille Dan Family Research Chair in Translational Cell Biology. Authors’ Contributions: N.A.M. contributed in study design, patient re- cruitment and enrollment, data analysis, and writing the manuscript. R.E. carried out the breast magnetic resonance image analysis of the study using image analysis and subjective methods and contributed in the draft- ing of the manuscript. P.C. assisted in outcome analysis design and in critically reviewing the manuscript. D.N. helped in drafting the manuscript. R.F.C. is the originator of the idea, designed the study, and edited the manuscript. The authors approved the submitted manuscript. Trial Registration: Clinicaltrials.gov NCT01129622. Financial disclosure/conflicts of interest: None reported. Supplemental digital content is available for this article. Direct URL cita- tions appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.menopause.org). Address correspondence to: Robert F. Casper MD, FRCS(C), Division of Reproductive Sciences, University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai HospitalYToronto, 25 Orde Street, Toronto, Ontario, Canada, M5T 3H7. E-mail: casper@lunenfeld.ca Menopause, Vol. 19, No. 4, 2012 1