Use of analgesic medications and risks of breast and endometrial cancer among women in the PLCO cohort
Local and systemic inflammation have been observed to be associated with increased risks of many cancers (1-3). Several studies have shown an inverse association between use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) and the risks of breast cancers (4-6). and endometrial cancers (7,8). However, findings have been mixed (9-13). We will test the hypothesis that regular use of anti-inflammatory medications is associated with reduced risks of breast cancer and endometrial cancers among postmenopausal women. We will be analyzing two cohorts based on questionnaires utilized in the PLCO cancer screening trial. The first analytic cohort will be comprised of female participants without history of malignancy at baseline, and who completed the baseline questionnaire and at least one annual follow-up. The second analytic cohort will include women who had no history of malignancy when they completed the supplemental questionnaire and then went on to complete at least one subsequent follow-up. Hazard ratios of the incidences of breast cancer and endometrial cancer by measures of NSAID use will be estimated using Cox proportional hazards regression.
To test the hypothesis that regular use of anti-inflammatory medications is associated with reduced risk of breast and endometrial cancers in postmenopausal women.
To consider whether risk associations are similar or different by time from questionnaire to diagnosis, by tumor subtypes, and by stage at diagnosis.
To assess the roles of some potential confounders/effect modifiers including but not limited to age, body mass index, parity, and years since menopause.
1. de Martel C, Franceschi S. Infections and cancer: established associations and new hypotheses. Crit Rev Oncol Hematol. Jun 2009;70(3):183-194.
2. Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. (2006) Inflammation and cancer: how hot is the link? Biochem Pharmacol 72(11):1605–1621.
3. Coussens LM, Werb Z. Inflammation and cancer. Nature. Dec 19-26 2002;420(6917):860-867.
4. Takkouche BR-MC, Etminan M (2008) Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. J Natl Cancer Inst 100(20):1420–1423.
5. Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84(9):1188–1192.
6. Harris RE, Beebe-Donk J, Doss H, Burr-Doss D (2005) Aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade. Oncol Rep 13:559–583.
7. Hasegawa K, Torii Y, Ishii R, Oe S, Kato R, Udagawa Y. Effects of a selective COX-2 inhibitor in patients with uterine endometrial cancers. Arch Gynecol Obstet. Dec 2011;284(6):1515-1521.
8. Neill AS, Nagle CM, Protani MM, Obermair A, Spurdle AB, Webb PM. Aspirin, nonsteroidal anti-inflammatory drugs, paracetamol and risk of endometrial cancer: a case-control study, systematic review and meta-analysis. Int J Cancer. Mar 1 2013;132(5):1146-1155.
9.Bosetti C, Gallus S, La Vecchia C: Aspirin and cancer risk: An updated quantitative review to 2005. Cancer Causes Control 17:871-888, 2006.
10. Garcia Rodriguez LA, Gonzalez-Perez A (2004) Risk of breast cancer among users of aspirin and other anti-inflammatory drugs. Br J Cancer 91(3):525–529.
11. Phipps AI, Anderson GL, Cochrane BB, et al. Migraine history, nonsteroidal anti-inflammatory drug use, and risk of postmenopausal endometrial cancer. Horm Cancer. Dec 2012;3(5-6):240-248.
12. Brasky TM, Moysich KB, Cohn DE, White E. Non-steroidal anti-inflammatory drugs and endometrial cancer risk in the VITamins And Lifestyle (VITAL) cohort. Gynecol Oncol. Jan 2013;128(1):113-119.
13. Setiawan VW, Matsuno RK, Lurie G, et al. Use of nonsteroidal anti-inflammatory drugs and risk of ovarian and endometrial cancer: the Multiethnic Cohort. Cancer Epidemiol Biomarkers Prev. Sep 2012;21(9):1441-1449.
Barbara Fuhrman, University of Arkansas for Medical Sciences
Bradley Martin, University of Arkansas for Medical Sciences