@article{0888487574bd49f1a7bfd10c9bfedc46,
title = "Aromatase inhibitor-induced modulation of breast density: Clinical and genetic effects",
abstract = "Background:Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy.Methods:Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment.Results:Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ≥20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed.Conclusion:Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes.",
keywords = "aromatase inhibitor, breast cancer, breast density, mammogram, polymorphism",
author = "Henry, {N. L.} and Chan, {H. P.} and J. Dantzer and Goswami, {C. P.} and L. Li and Skaar, {T. C.} and Rae, {J. M.} and Z. Desta and N. Khouri and R. Pinsky and S. Oesterreich and C. Zhou and L. Hadjiiski and S. Philips and J. Robarge and Nguyen, {A. T.} and Storniolo, {A. M.} and Flockhart, {D. A.} and Hayes, {D. F.} and Helvie, {M. A.} and V. Stearns",
note = "Funding Information: This study was supported in part by Pharmacogenetics Research Network Grant no. U-01 GM61373 (to DAF) and Clinical Pharmacology training Grant 5T32-GM08425 (to DAF) from the National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD, and by Grant Numbers M01-RR000042 (UM), M01-RR00750 (IU), and M01-RR00052 (JHU) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. In addition, these studies were supported by grants from Pfizer, Inc. (to DFH), Novartis Pharma AG (to DFH), and the Fashion Footwear Association of New York/ QVC Presents Shoes on Sale (to DFH). Study medication was provided by Pfizer (exemestane) and Novartis (letrozole). NLH receives research funding from AstraZeneca, Eli Lilly, sanofi Aventis, BiPar Pharmaceuticals, and Exelixis. JMR received a research grant from Pfizer. AMS receives research funding from Novartis and Pfizer. DAF receives research funding from Novartis and Pfizer. DFH receives research funding from AstraZeneca, Novartis, Pfizer, Veridex, and Janssen. VS receives research funding from Abraxis (Celegene), Merck, Novartis, and Pfizer. MAH receives research funding from General Electric Healthcare. We thank the participating patients and research study staff at each of the clinical trial sites.",
year = "2013",
month = oct,
day = "29",
doi = "10.1038/bjc.2013.587",
language = "English (US)",
volume = "109",
pages = "2331--2339",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "9",
}