Abstract
Objective
We examined the association between NSAID use and breast cancer recurrence in a prospective cohort of 2,292 early-stage breast cancer survivors diagnosed from 1997 to 2000 participating in the Life After Cancer Epidemiology (LACE) Study.
Methods
From 2000 to 2002, mailed questionnaires were used to obtain information on aspirin, ibuprofen, and other NSAID use and subsequent breast cancer events. A total of 270 recurrences (local, regional, and distant disease and new primary breast cancers) were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI), adjusting for age at diagnosis, race, cancer stage, tamoxifen treatment, chemotherapy use, body mass index, and cyclooxygenase-2 (COX2) inhibitor use.
Results
Current, regular use (at least three days per week at time of questionnaire administration) of ibuprofen (RR, 0.56; 95% CI, 0.32–0.98), but not aspirin (RR, 1.09; 95% CI, 0.74–1.61), was associated with a statistically significant decreased risk of breast cancer recurrence. The combination of ibuprofen and other non-aspirin NSAIDs such as naproxen and sulindac reflected a similar reduction in risk (RR, 0.56; 95% CI, 0.33–0.95). No association was found for the non-NSAID analgesic acetaminophen.
Conclusion
Our findings provide support for an inverse association between current, regular ibuprofen use and breast cancer recurrence.
Similar content being viewed by others
References
http://http://www.cancer/. (2006) org, American Cancer Society
Harris RE, Chlebowski RT, Jackson RD, et al (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63(18):6096–6101
Khuder SA, Mutgi AB (2001) Breast cancer and NSAID use: a meta-analysis. Br J Cancer 84(9):1188–1192
Moorman PG, Grubber JM, Millikan RC, Newman B (2003) Association between non-steroidal anti-inflammatory drugs (NSAIDs) and invasive breast cancer and carcinoma in situ of the breast. Cancer Causes Control 14(10):915–922
Swede H, Mirand AL, Menezes RJ, Moysich KB (2005) Association of regular aspirin use and breast cancer risk. Oncology 68(1): 40–47
Terry MB, Gammon MD, Zhang FF, et al (2004) Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. Jama 291(20):2433–2440
Zhang Y, Coogan PF, Palmer JR, Strom BL, Rosenberg L (2005) Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case-Control Surveillance Study revisited. Am J Epidemiol 162(2):165–170
Gonzalez-Perez A, Garcia Rodriguez LA, Lopez-Ridaura R (2003) Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 3:28
Cook NR, Lee IM, Gaziano JM et al (2005) Low-dose aspirin in the primary prevention of cancer: the Women’s Health Study: a randomized controlled trial. Jama 294(1):47–55
Jacobs EJ, Thun MJ, Connell CJ et al (2005) Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort. Cancer Epidemiol Biomarkers Prev 14(1):261–264
Marshall SF, Bernstein L, Anton-Culver H et al (2005) Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst 97(11):805–812
Caan B, Sternfeld B, Gunderson E, Coates A, Quesenberry C, Slattery ML (2005) Life After Cancer Epidemiology (LACE) Study: a cohort of early stage breast cancer survivors (United States). Cancer Causes Control 16(5):545–556
Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA (2005) Physical activity and survival after breast cancer diagnosis. Jama 293(20):2479–2486
Hosmer DW, Lemeshow S (1999) Applied survival analysis: regression modeling of time to event data. John Wiley & Sons, Inc, New York
Ulrich CM, Bigler J, Potter JD (2006) Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer 6(2):130–140
Meric JB, Rottey S, Olaussen K et al (2006) Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol 59(1):51–64
Alshafie GA, Harris RE, Robertson FM Parrett ML Ross M Abou-Issa H (1999) Comparative chemopreventive activity of ibuprofen and N-(4-hydroxyphenyl) retinamide against the development and growth of rat mammary adenocarcinomas. Anticancer Res 19(4B):3031–3036
Robertson FM, Parrett ML, Joarder FS, et al (1998) Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinomas. Cancer Lett 122(1–2):165–175
Arun B, Hortobagyi GN (2002) Progress in breast cancer chemoprevention. Endocr Relat Cancer 9(1):15–32
Hwang D, Scollard D, Byrne J, Levine E (1998) Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. J Natl Cancer Inst 90(6):455–460
Parrett M, Harris R, Joarder F, Ross M, Clausen K, Robertson F (1997) Cyclooxygenase-2 gene expression in human breast cancer. Int J Oncol 10:503–508
Costa C, Soares R, Reis-Filho JS, Leitao D, Amendoeira I, Schmitt FC (2002) Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer. J Clin Pathol 55(6):429–434
Ristimaki A, Sivula A, Lundin J, et al (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62(3):632–635
Blair CK, Sweeney C, Anderson KE, Folsom AR (2006) NSAID use and survival after breast cancer diagnosis in post-menopausal women. Breast Cancer Res Treat
Acknowledgments
This study was funded by the National Cancer Institute (R01 CA80027) and by the Utah Cancer Registry (N01 PC67000), with additional support from the State of Utah Department of Health. We thank Charles Quesenberry, Ph.D. for his biostatistical support and Robert Reynolds, M.P.H. for his programming support. We thank all LACE Study staff and participants.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kwan, M.L., Habel, L.A., Slattery, M.L. et al. NSAIDs and breast cancer recurrence in a prospective cohort study. Cancer Causes Control 18, 613–620 (2007). https://doi.org/10.1007/s10552-007-9003-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10552-007-9003-y