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Aspirin and Breast Cancer Prevention

  • Risk, Prevention, and Screening (DL Hershman, Section Editor)
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Abstract

Over the past decade, breast cancer chemoprevention has made substantial progress, particularly with selective estrogen receptor modulators and aromatase inhibitors. A new generation of chemopreventive agents modulating the non-endocrine biochemical pathways has been studied so far, including the 100-year-old drug aspirin. Commonly known as pain-reliever, aspirin may also influence breast carcinogenesis through a number of mechanisms, including decreased production of prostaglandins, which can inhibit angiogenesis and inhibit apoptosis, inhibition of the cyclo-oxygenase enzymatic pathways and stimulation of the AMPk pathway leading to decreased proliferation and increased autophagy. Long-term follow-up of randomized trials of aspirin in prevention of vascular events showed that daily aspirin reduced the incidence of colorectal cancer and several other cancers, including a borderline effect on breast cancer incidence. In the present review, we discuss the potential role aspirin in breast cancer prevention comparing data from observational studies with those from the randomized trials.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  PubMed  CAS  Google Scholar 

  2. Baqai T, Shousha S. Oestrogen receptor negativity as a marker for high-grade ductal carcinoma in situ of the breast. Histopathology. 2003;42:440–7.

    Article  PubMed  CAS  Google Scholar 

  3. Provenzano E, Hopper JL, Giles GG, et al. Biological markers that predict clinical recurrence in ductal carcinoma in situ of the breast. Eur J Cancer. 2003;39:622–30.

    Article  PubMed  CAS  Google Scholar 

  4. Cazzaniga M, Bonanni B. Prevention of ER-negative breast cancer: where do we stand? Eur J Cancer Prev. 2012;21:171–81.

    Article  PubMed  Google Scholar 

  5. Subbaramaiah K, Morris PG, Zhou XK, et al. Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. Cancer Discov. 2012;2:356–65.

    Article  PubMed  CAS  Google Scholar 

  6. Simmons DL, Botting RM, Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev. 2004;56:387–437.

    Article  PubMed  CAS  Google Scholar 

  7. Ulrich CM, Bigler J, Potter JD. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer. 2006;6:130–40.

    Article  PubMed  CAS  Google Scholar 

  8. Zhao Y, Agarwal VR, Mendelson CR, et al. Estrogen biosynthesis proximal to a breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene. Endocrinology. 1996;137:5739–42.

    Article  PubMed  CAS  Google Scholar 

  9. Brueggemeier RW, Quinn AL, Parrett ML, et al. Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett. 1999;140:27–35.

    Article  PubMed  CAS  Google Scholar 

  10. Elvin JA, Yan C, Matzuk MM. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Proc Natl Acad Sci U S A. 2000;97:10288–93.

    Article  PubMed  CAS  Google Scholar 

  11. Kopp E, Ghosh S. Inhibition of NF-κB by sodium salicylate and aspirin. Science. 1994;265:956–9.

    Article  PubMed  CAS  Google Scholar 

  12. Stark LA, Reid K, Sansom OJ, et al. Aspirin activates the NF-κB signalling pathway and induces apoptosis in intestinal neoplasia in two in vivo models of human colorectal cancer. Carcinogenesis. 2007;28:968–76.

    Article  PubMed  CAS  Google Scholar 

  13. Yan F, He Q, Hu X, et al. Direct regulation of caspase3 by the transcription factor AP2alpha is involved in aspirininduced apoptosis in MDAMB453 breast cancer cells. Mol Med Rep. 2013;7:909–14.

    PubMed  CAS  Google Scholar 

  14. Borthwick GM, Johnson AS, Partington M, et al. Therapeutic levels of aspirin and salicylate directly inhibit a model of angiogenesis through a Cox-independent mechanism. FASEB J. 2006;20:2009–16.

    Article  PubMed  CAS  Google Scholar 

  15. Fogarty S, Hardie DG. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim Biophys Acta. 1804;2010:581–91.

    Google Scholar 

  16. Chen D, Pamu S, Cui Q, et al. Novel epigallocatechin gallate (EGCG) analogs activate AMP-activated protein kinase pathway and target cancer stem cells. Bioorg Med Chem. 2012;20:3031–7.

    Article  PubMed  CAS  Google Scholar 

  17. Rattan R, Giri S, Singh AK, et al. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. J Biol Chem. 2005;280:39582–93.

    Article  PubMed  CAS  Google Scholar 

  18. Hirsch HA, Iliopoulos D, Tsichlis PN, et al. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 2009;69:7507–11.

    Article  PubMed  CAS  Google Scholar 

  19. • Hawley SA, Fullerton MD, Ross FA, et al. The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 2012;336:918–22. AMPK activation could explain some beneficial effects of aspirin in humans.

    Article  PubMed  CAS  Google Scholar 

  20. Din FV, Valanciute A, Houde VP, et al. Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology. 2012;142:1504–15.

    Article  PubMed  CAS  Google Scholar 

  21. Terry MB, Gammon MD, Zhang FF, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA. 2004;291:2433–40.

    Article  PubMed  CAS  Google Scholar 

  22. Holmes MD, Chen WY, Li L, et al. Aspirin intake and survival after breast cancer. J Clin Oncol. 2010;28:1467–72.

    Article  PubMed  CAS  Google Scholar 

  23. Holmes MD, Chen WY, Schnitt SJ, et al. COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin. Breast Cancer Res Treat. 2011;130:657–62.

    Article  PubMed  CAS  Google Scholar 

  24. • Zhang X, Smith-Warner SA, Collins LC, et al. Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence. J Clin Oncol. 2012;30:3468–77. A recent update of the Nurses’ Health Study on breast cancer mortality risk according to number of days per week of aspirin use.

    Article  PubMed  CAS  Google Scholar 

  25. Li Y, Brasky TM, Nie J, et al. Use of nonsteroidal anti-inflammatory drugs and survival following breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev. 2012;21:239–42.

    Article  PubMed  CAS  Google Scholar 

  26. Khuder SA, Mutgi AB. Breast cancer and NSAID use: a meta-analysis. Br J Cancer. 2001;84:1188–92.

    Article  PubMed  CAS  Google Scholar 

  27. Mangiapane S, Blettner M, Schlattmann P. Aspirin use and breast cancer risk: a meta-analysis and meta-regression of observational studies from 2001 to 2005. Pharmacoepidemiol Drug Saf. 2008;17:115–24.

    Article  PubMed  Google Scholar 

  28. Takkouche B, Regueira-Mendez C. Etminan M: breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. J Natl Cancer Inst. 2008;100:1439–47.

    Article  PubMed  CAS  Google Scholar 

  29. Zhao YS, Zhu S, Li XW, et al. Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis. Breast Cancer Res Treat. 2009;117:141–50.

    Article  PubMed  CAS  Google Scholar 

  30. Bosetti C, Rosato V, Gallus S, et al. Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol. 2012;23:1403–15.

    Article  PubMed  CAS  Google Scholar 

  31. Luo T, Yan HM, He P, et al. Aspirin use and breast cancer risk: a meta-analysis. Breast Cancer Res Treat. 2012;131:581–7.

    Article  PubMed  CAS  Google Scholar 

  32. Cook NR, Lee IM, Gaziano JM, 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.

    Article  PubMed  CAS  Google Scholar 

  33. •• Rothwell PM, Wilson M, Price JF, et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379:1591–601. The most recent study of incident cancers during randomized controlled trials.

    Article  PubMed  CAS  Google Scholar 

  34. Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 2012;13:518–27.

    Article  PubMed  CAS  Google Scholar 

  35. Gorelick PB, Weisman SM. Risk of hemorrhagic stroke with aspirin use: an update. Stroke. 2005;36:1801–7.

    Article  PubMed  CAS  Google Scholar 

  36. Lee M, Cryer B, Feldman M. Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury. Ann Intern Med. 1994;120:184–9.

    Article  PubMed  CAS  Google Scholar 

  37. Baron JA, Cole BF, Sandler RS, et al. A randomised trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003;348:891–9.

    Article  PubMed  CAS  Google Scholar 

  38. Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ. 1995;310:827–30.

    Article  PubMed  CAS  Google Scholar 

  39. Wald NJ, Morris JK, Law MR. Aspirin in the prevention of cancer. Lancet. 2011;377:1649–2.

    Article  PubMed  CAS  Google Scholar 

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Conflict of Interest

Matteo Lazzeroni, Marilena Petrera, Domenico Marra, and Andrea DeCensi declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Correspondence to Andrea DeCensi.

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Lazzeroni, M., Petrera, M., Marra, D. et al. Aspirin and Breast Cancer Prevention. Curr Breast Cancer Rep 5, 202–207 (2013). https://doi.org/10.1007/s12609-013-0115-y

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