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Influence of analgesic medication use on circulating estrogens and estrogen metabolites (EM) in samples of postmenopausal women from the PLCO cohort

Principal Investigator
Name
Barbara Fuhrman
Degrees
Ph.D.
Institution
University of Arkansas for Medical Sciences
Position Title
Assistant Professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-61
Initial CDAS Request Approval
Feb 14, 2014
Title
Influence of analgesic medication use on circulating estrogens and estrogen metabolites (EM) in samples of postmenopausal women from the PLCO cohort
Summary
Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) work through inhibition of COX-1 and COX-2, and have also been observed to decrease, in vitro, expression of the CYP 19 gene and aromatase activity in breast cancer cells. Several, but not all studies have shown beneficial effects of aspirin and NSAID use on estrogen profiles (1, 2) and on breast cancer risk (3, 4). We will test the hypothesis that analgesic medications influence serum estrogen metabolite profiles in samples of postmenopausal women who went on to develop breast cancer, and those who did not. Participants were previously selected as breast cancer cases and controls in a previous study of estrogen metabolism and breast cancer risk (5). General linear models will be used to estimate associations between the use of analgesic medications and estrogen metabolites while adjusting for body mass index (BMI), years since menopause, and other breast cancer risk factors. Finally, we will test for effect modification by case status, obesity, history of hormone replacement therapy (HRT) use and other breast cancer risk factors.
References:
1. Hudson AG, Gierach GL, Modugno F, Simpson J, Wilson JW, Evans RW, Vogel VG, Weissfeld JL 2008 Nonsteroidal anti-inflammatory drug use and serum total estradiol in postmenopausal women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 17:680-687
2. Gates MA, Tworoger SS, Eliassen AH, Missmer SA, Hankinson SE 2010 Analgesic use and sex steroid hormone concentrations in postmenopausal women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 19:1033-1041
3. Zhang X, Smith-Warner SA, Collins LC, Rosner B, Willett WC, Hankinson SE 2012 Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 30:3468-3477
4. Luo T, Yan HM, He P, Luo Y, Yang YF, Zheng H 2012 Aspirin use and breast cancer risk: a meta-analysis. Breast cancer research and treatment 131:581-587
5. Fuhrman BJ, Schairer C, Gail MH, Boyd-Morin J, Xu X, Sue LY, Buys SS, Isaacs C, Keefer LK, Veenstra TD, Berg CD, Hoover RN, Ziegler RG 2012 Estrogen metabolism and risk of breast cancer in postmenopausal women. Journal of the National Cancer Institute 104:326-339.
Aims

We will conduct a cross sectional analysis of the association of analgesic use with circulating estrogens and estrogen metabolites in samples of postmenopausal women with and without subsequent diagnoses of breast cancer, drawn from the PLCO cancer screening trial cohort.
1. To assess the association of analgesic medication use and estrogen metabolite profile in postmenopausal women with and without subsequent breast cancer diagnoses.
2. To assess the role of effect modification by BMI, years since menopause, HRT use, and other breast cancer risk factors.
3. To assess whether associations of NSAID use and estrogen metabolite profiles differ by case status, and among cases, by other tumor characteristics including time to diagnosis, stage, histologic grade, and hormone receptor status.

Collaborators

Upasana Tiwari, M.D., University of Arkansas for Medical Sciences
Kayleigh Majercak, B.S., University of Arkansas for Medical Sciences
Catherine Schairer, Ph.d., Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH
Regina Ziegler, Ph.d. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH
Barbara Fuhrman, Ph.d., University of Arkansas for Medical Sciences

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