Advertisement
Mayo Clinic Proceedings Home

Personalizing Aspirin Use for Targeted Breast Cancer Chemoprevention in Postmenopausal Women

Published:December 08, 2015DOI:https://doi.org/10.1016/j.mayocp.2015.10.018

      Abstract

      Objective

      To evaluate the association of aspirin and other nonsteroidal anti-inflammatory drugs with the incidence of postmenopausal breast cancer for risk subgroups defined by selected nonmodifiable or difficult to modify breast cancer risk factors in order to better understand the potential risk-benefit ratio for targeted chemoprevention.

      Patients and Methods

      Postmenopausal women with no history of cancer on July 1, 1992 (N=26,580), were prospectively followed up through December 31, 2005, for breast cancer incidence (N=1581). Risk subgroups were defined on the basis of family history of breast cancer, age at menarche, age at menopause, parity/age at first live birth, personal history of benign breast disease, and body mass index. Hazard ratios (HRs) and 95% CIs adjusted for other breast cancer risk factors were estimated using Cox models.

      Results

      Aspirin use was associated with a lower incidence of breast cancer for women with a family history of breast cancer (HR, 0.62 for 6 or more times per week vs never use; 95% CI, 0.41-0.93) and those with a personal history of benign breast disease (HR, 0.69; 95% CI, 0.50-0.95) but not for women in higher-risk subgroups for age at menarche, age at menopause, parity/age at first live birth, or body mass index. In contrast, inverse associations with aspirin use were observed in all lower-risk subgroups. Nonsteroidal anti-inflammatory drug use had no association with breast cancer incidence.

      Conclusion

      On the basis of their increased risk of breast cancer, postmenopausal women with a family history of breast cancer or a personal history of benign breast disease could potentially be targeted for aspirin chemoprevention studies. Future studies are needed to confirm these findings.

      Abbreviations and Acronyms:

      BMI (body mass index), COX (cyclooxygenase), HR (hazard ratio), NNT (number needed to treat), NSAID (nonsteroidal anti-inflammatory drug), RR (relative risk)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Edwards B.K.
        • Noone A.M.
        • Mariotto A.B.
        • et al.
        Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer.
        Cancer. 2014; 120: 1290-1314
      1. National Cancer Institute. SEER Stat Fact Sheets: Breast Cancer Statistics. SEER website. http://seer.cancer.gov/statfacts/html/breast.html. Accessed August 10, 2015.

        • Rostom A.
        • Dubé C.
        • Lewin G.
        • et al.
        • US Preventive Services Task Force
        Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U. S. Preventive Services Task Force.
        Ann Intern Med. 2007; 146: 376-389
        • Bosetti C.
        • Rosato V.
        • Gallus S.
        • Cuzick J.
        • La Vecchia C.
        Aspirin and cancer risk: a quantitative review to 2011.
        Ann Oncol. 2012; 23: 1403-1415
        • Harris R.E.
        • Beebe-Donk J.
        • Doss H.
        • Burr Doss D.
        Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review).
        Oncol Rep. 2005; 13: 559-583
        • Cuzick J.
        • Otto F.
        • Baron J.A.
        • et al.
        Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement.
        Lancet Oncol. 2009; 10: 501-507
        • Thun M.J.
        • Jacobs E.J.
        • Patrono C.
        The role of aspirin in cancer prevention.
        Nat Rev Clin Oncol. 2012; 9: 259-267
        • Rothwell P.M.
        • Price J.F.
        • Fowkes F.G.
        • et al.
        Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials.
        Lancet. 2012; 379: 1602-1612
        • Hial V.
        • Horakova Z.
        • Shaff F.E.
        • Beaven M.A.
        Alteration of tumor growth by aspirin and indomethacin: studies with two transplantable tumors in mouse.
        Eur J Pharmacol. 1976; 37: 367-376
        • Bennett A.
        • Curwain B.P.
        Effects of aspirin-like drugs on canine gastric mucosal blood flow and acid secretion.
        Br J Pharmacol. 1977; 60: 499-504
        • Karmali R.A.
        • Welt S.
        • Thaler H.T.
        • Lefevre F.
        Prostaglandins in breast cancer: relationship to disease stage and hormone status.
        Br J Cancer. 1983; 48: 689-696
        • Watson J.
        • Chuah S.Y.
        Prostaglandins, steroids and human mammary cancer.
        Eur J Cancer Clin Oncol. 1985; 21: 1051-1055
        • Dannenberg A.J.
        • Lippman S.M.
        • Mann J.R.
        • Subbaramaiah K.
        • DuBois R.N.
        Cyclooxygenase-2 and epidermal growth factor receptor: pharmacologic targets for chemoprevention.
        J Clin Oncol. 2005; 23: 254-266
        • Su B.
        • Diaz-Cruz E.S.
        • Landini S.
        • Brueggemeier R.W.
        Suppression of aromatase in human breast cells by a cyclooxygenase-2 inhibitor and its analog involves multiple mechanisms independent of cyclooxygenase-2 inhibition.
        Steroids. 2008; 73: 104-111
        • Schreinemachers D.M.
        • Everson R.B.
        Aspirin use and lung, colon, and breast cancer incidence in a prospective study.
        Epidemiology. 1994; 5: 138-146
        • Harris R.E.
        • Namboodiri K.
        • Stellman S.D.
        • Wynder E.L.
        Breast cancer and NSAID use: heterogeneity of effect in a case-control study.
        Prev Med. 1995; 24: 119-120
        • Harris R.E.
        • Namboodiri K.K.
        • Farrar W.B.
        Nonsteroidal antiinflammatory drugs and breast cancer.
        Epidemiology. 1996; 7: 203-205
        • Coogan P.F.
        • Rao S.R.
        • Rosenberg L.
        • et al.
        The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer.
        Prev Med. 1999; 29: 72-76
        • Sharpe C.R.
        • Collet J.P.
        • McNutt M.
        • Belzile E.
        • Boivin J.F.
        • Hanley J.A.
        Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage.
        Br J Cancer. 2000; 83: 112-120
        • Terry M.B.
        • Gammon M.D.
        • Zhang F.F.
        • et al.
        Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk.
        JAMA. 2004; 291: 2433-2440
        • Marshall S.F.
        • Bernstein L.
        • Anton-Culver H.
        • et al.
        Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status.
        J Natl Cancer Inst. 2005; 97: 805-812
        • Rahme E.
        • Ghosn J.
        • Dasgupta K.
        • Rajan R.
        • Hudson M.
        Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer.
        BMC Cancer. 2005; 5: 159
        • Zhang Y.
        • Coogan P.F.
        • Palmer J.R.
        • Strom B.L.
        • Rosenberg L.
        Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case-Control Surveillance Study revisited.
        Am J Epidemiol. 2005; 162: 165-170
        • Kirsh V.A.
        • Kreiger N.
        • Cotterchio M.
        • Sloan M.
        • Theis B.
        Nonsteroidal antiinflammatory drug use and breast cancer risk: subgroup findings.
        Am J Epidemiol. 2007; 166: 709-716
        • Ready A.
        • Velicer C.M.
        • McTiernan A.
        • White E.
        NSAID use and breast cancer risk in the VITAL cohort.
        Breast Cancer Res Treat. 2008; 109: 533-543
        • Harris R.E.
        • Chlebowski R.T.
        • Jackson R.D.
        • et al.
        Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative.
        Cancer Res. 2003; 63: 6096-6101
        • Egan K.M.
        • Stampfer M.J.
        • Giovannucci E.
        • Rosner B.A.
        • Colditz G.A.
        Prospective study of regular aspirin use and the risk of breast cancer.
        J Natl Cancer Inst. 1996; 88: 988-993
        • Jacobs E.J.
        • Thun M.J.
        • Connell C.J.
        • et al.
        Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort.
        Cancer Epidemiol Biomarkers Prev. 2005; 14: 261-264
        • Gill J.K.
        • Maskarinec G.
        • Wilkens L.R.
        • Pike M.C.
        • Henderson B.E.
        • Kolonel L.N.
        Nonsteroidal antiinflammatory drugs and breast cancer risk: the multiethnic cohort.
        Am J Epidemiol. 2007; 166: 1150-1158
        • Gierach G.L.
        • Lacey Jr., J.V.
        • Schatzkin A.
        • et al.
        Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study.
        Breast Cancer Res. 2008; 10: R38
        • Johnson T.W.
        • Anderson K.E.
        • Lazovich D.
        • Folsom A.R.
        Association of aspirin and other nonsteroidal anti-inflammatory drug use with breast cancer.
        Cancer Epidemiol Biomarkers Prev. 2002; 11: 1586-1591
        • Hortobagyi G.N.
        • Brown P.H.
        Two good choices to prevent breast cancer: great taste, less filling.
        Cancer Prev Res (Phila). 2010; 3: 681-685
        • Folsom A.R.
        • Kaye S.A.
        • Prineas R.J.
        • Potter J.D.
        • Gapstur S.M.
        • Wallace R.B.
        Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal women.
        Am J Epidemiol. 1990; 131: 794-803
        • Bisgard K.M.
        • Folsom A.R.
        • Hong C.P.
        • Sellers T.A.
        Mortality and cancer rates in nonrespondents to a prospective study of older women: 5-year follow-up.
        Am J Epidemiol. 1994; 139: 990-1000
        • Yang X.R.
        • Chang-Claude J.
        • Goode E.L.
        • et al.
        Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.
        J Natl Cancer Inst. 2011; 103: 250-263
        • Gail M.H.
        • Brinton L.A.
        • Byar D.P.
        • et al.
        Projecting individualized probabilities of developing breast cancer for white females who are being examined annually.
        J Natl Cancer Inst. 1989; 81: 1879-1886
      2. Ries LAG, Melbert D, Krapcho M, et al, eds. SEER Cancer Statistics Review, 1975-2005. SEER website. http://seer.cancer.gov/csr/1975_2005/. Published 2008. Accessed August 10, 2015.

        • Bardia A.
        • Olson J.E.
        • Vachon C.M.
        • et al.
        Effect of aspirin and other NSAIDs on postmenopausal breast cancer incidence by hormone receptor status: results from a prospective cohort study.
        Breast Cancer Res Treat. 2011; 126: 149-155
        • Korn E.L.
        • Graubard B.I.
        • Midthune D.
        Time-to-event analysis of longitudinal follow-up of a survey: choice of the time-scale.
        Am J Epidemiol. 1997; 145: 72-80
        • Suissa D.
        • Brassard P.
        • Smiechowski B.
        • Suissa S.
        Number needed to treat is incorrect without proper time-related considerations.
        J Clin Epidemiol. 2012; 65: 42-46
        • Zhang X.
        • Smith-Warner S.A.
        • Collins L.C.
        • Rosner B.
        • Willett W.C.
        • Hankinson S.E.
        Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence.
        J Clin Oncol. 2012; 30: 3468-3477
        • Langman M.J.
        • Cheng K.K.
        • Gilman E.A.
        • Lancashire R.J.
        Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database.
        BMJ. 2000; 320: 1642-1646
        • Luo T.
        • Yan H.M.
        • He P.
        • Luo Y.
        • Yang Y.F.
        • Zheng H.
        Aspirin use and breast cancer risk: a meta-analysis.
        Breast Cancer Res Treat. 2012; 131: 581-587
        • Cook N.R.
        • Lee I.M.
        • Gaziano J.M.
        • et al.
        Low-dose aspirin in the primary prevention of cancer: the Women's Health Study; a randomized controlled trial.
        JAMA. 2005; 294: 47-55
        • Holmes M.D.
        • Chen W.Y.
        • Li L.
        • Hertzmark E.
        • Spiegelman D.
        • Hankinson S.E.
        Aspirin intake and survival after breast cancer.
        J Clin Oncol. 2010; 28: 1467-1472
        • Blair C.K.
        • Sweeney C.
        • Anderson K.E.
        • Folsom A.R.
        NSAID use and survival after breast cancer diagnosis in post-menopausal women.
        Breast Cancer Res Treat. 2007; 101: 191-197
        • Zhong S.
        • Zhang X.
        • Chen L.
        • Ma T.
        • Tang J.
        • Zhao J.
        Association between aspirin use and mortality in breast cancer patients: a meta-analysis of observational studies.
        Breast Cancer Res Treat. 2015; 150: 199-207
        • Colditz G.A.
        • Rosner B.A.
        • Chen W.Y.
        • Holmes M.D.
        • Hankinson S.E.
        Risk factors for breast cancer according to estrogen and progesterone receptor status.
        J Natl Cancer Inst. 2004; 96: 218-228
        • Gallicchio L.
        • McSorley M.A.
        • Newschaffer C.J.
        • et al.
        Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease.
        Cancer. 2006; 106: 1443-1452
        • Liao X.
        • Lochhead P.
        • Nishihara R.
        • et al.
        Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival.
        N Engl J Med. 2012; 367: 1596-1606
        • Choi B.H.
        • Chakraborty G.
        • Baek K.
        • Yoon H.S.
        Aspirin-induced Bcl-2 translocation and its phosphorylation in the nucleus trigger apoptosis in breast cancer cells.
        Exp Mol Med. 2013; 45: e47
        • Huang L.
        • Wong C.C.
        • Mackenzie G.G.
        • et al.
        Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress.
        BMC Cancer. 2014; 14: 141
        • González-Pérez A.
        • García Rodríguez L.A.
        • López-Ridaura R.
        Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis.
        BMC Cancer. 2003; 3: 28
        • Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group
        The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.
        N Engl J Med. 1994; 330: 1029-1035
        • Lonn E.
        • Bosch J.
        • Yusuf S.
        • et al.
        • HOPE and HOPE-TOO Trial Investigators
        Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial.
        JAMA. 2005; 293: 1338-1347
        • Lippman S.M.
        • Klein E.A.
        • Goodman P.J.
        • et al.
        Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT).
        JAMA. 2009; 301: 39-51
        • Gaziano J.M.
        • Glynn R.J.
        • Christen W.G.
        • et al.
        Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial.
        JAMA. 2009; 301: 52-62
        • Brewster A.M.
        • Patterson S.L.
        • Forman M.R.
        • et al.
        Conference Report: Eighth Annual AACR International Conference on Frontiers in Cancer Prevention Research.
        Cancer Prev Res (Phila). 2010; 3: 1044-1048
        • Cuzick J.
        • DeCensi A.
        • Arun B.
        • et al.
        Preventive therapy for breast cancer: a consensus statement.
        Lancet Oncol. 2011; 12: 496-503
        • Arun B.
        • Dunn B.K.
        • Ford L.G.
        • Ryan A.
        Breast cancer prevention trials: large and small trials.
        Semin Oncol. 2010; 37: 367-383
        • Uray I.P.
        • Brown P.H.
        Chemoprevention of hormone receptor-negative breast cancer: new approaches needed.
        Recent Results Cancer Res. 2011; 188: 147-162