Skip to main content

Advertisement

SpringerLink
Log in

Aspirin use is associated with lower mammographic density in a large screening cohort

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Observational and biologic studies suggest that aspirin is a promising prevention therapy for breast cancer. However, clinical trials to date have not corroborated this evidence, potentially due to study design. We evaluated the effect of aspirin on mammographic density (MD), an established modifiable risk factor for breast cancer.

Methods

Electronic medical records from the University of Pennsylvania were evaluated for women who underwent screening mammography, saw their primary care provider, and had a confirmed list of medications during 2012–2013. Logistic regression was performed to test for associations between clinically recorded MD and aspirin use, after adjusting for age, body mass index (BMI), and ethnicity.

Results

We identified 26,000 eligible women. Mean age was 57.3, mean BMI was 28.9 kg/m2, 41% were African American, and 19.7% reported current aspirin use. Aspirin users were significantly older and had higher BMI. There was an independent, inverse association between aspirin use and MD (P trend < 0.001). Women with extremely dense breasts were less likely to be aspirin users than women with scattered fibroglandular density (OR 0.73; 95% CI 0.57–0.93). This association was stronger for younger women (P = 0.0002) and for African Americans (P = 0.011). The likelihood of having dense breasts decreased with aspirin dose (P trend = 0.007), suggesting a dose response.

Conclusions

We demonstrate an independent association between aspirin use and lower MD in a large, diverse screening cohort. This association was stronger for younger and African American women: two groups at greater risk for ER− breast cancer. These results contribute to the importance of investigating aspirin for breast cancer prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Fisher B et al (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90(18):1371–1388

    Article  CAS  PubMed  Google Scholar 

  2. Goss PE et al (2011) Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 364(25):2381–2391

    Article  CAS  PubMed  Google Scholar 

  3. Cuzick J et al (2014) Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 383(9922):1041–1048

    Article  CAS  PubMed  Google Scholar 

  4. Dent SF et al (2011) Aromatase inhibitor therapy: toxicities and management strategies in the treatment of postmenopausal women with hormone-sensitive early breast cancer. Breast Cancer Res Treat 126(2):295–310

    Article  CAS  PubMed  Google Scholar 

  5. Makubate B et al (2013) Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer 108(7):1515–1524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ready A et al (2008) NSAID use and breast cancer risk in the VITAL cohort. Breast Cancer Res Treat 109(3):533–543

    Article  CAS  PubMed  Google Scholar 

  7. Kirsh VA et al (2007) Nonsteroidal antiinflammatory drug use and breast cancer risk: subgroup findings. Am J Epidemiol 166(6):709–716

    Article  PubMed  Google Scholar 

  8. Thun MJ, Jacobs EJ, Patrono C (2012) The role of aspirin in cancer prevention. Nat Rev Clin Oncol 9(5):259–267

    Article  CAS  PubMed  Google Scholar 

  9. Bosetti C et al (2012) Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol 23(6):1403–1415

    Article  CAS  PubMed  Google Scholar 

  10. Algra AM, Rothwell PM (2012) Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 13(5):518–527

    Article  CAS  PubMed  Google Scholar 

  11. Bennett A et al (1977) Prostaglandins and breast cancer. Lancet 2(8039):624–626

    Article  CAS  PubMed  Google Scholar 

  12. Sotiriou C et al (1999) The aspirin metabolite salicylate inhibits breast cancer cells growth and their synthesis of the osteolytic cytokines interleukins-6 and -11. Anticancer Res 19(4B):2997–3006

    CAS  PubMed  Google Scholar 

  13. Kundu N et al (2001) Increased cyclooxygenase-2 (cox-2) expression and activity in a murine model of metastatic breast cancer. Int J Cancer 93(5):681–686

    Article  CAS  PubMed  Google Scholar 

  14. Mangiapane S, Blettner M, Schlattmann P (2008) Aspirin use and breast cancer risk: a meta-analysis and meta-regression of observational studies from 2001 to 2005. Pharmacoepidemiol Drug Saf 17(2):115–124

    Article  PubMed  Google Scholar 

  15. Luo T et al (2012) Aspirin use and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 131(2):581–587

    Article  CAS  PubMed  Google Scholar 

  16. Bardia A et al (2011) 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 126(1):149–155

    Article  CAS  PubMed  Google Scholar 

  17. Brasky TM et al (2011) Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype. Cancer Causes Control 22(7):965–975

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rahme E et al (2005) Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer. BMC Cancer 5:159

    Article  PubMed  PubMed Central  Google Scholar 

  19. Harris RE et al (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women’s Health Initiative. Cancer Res 63(18):6096–6101

    CAS  PubMed  Google Scholar 

  20. Rothwell PM et al (2012) 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 379(9826):1602–1612

    Article  CAS  PubMed  Google Scholar 

  21. Cook NR et al (2013) Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial. Ann Intern Med 159(2):77–85

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zhang SM et al (2008) Low-dose aspirin and breast cancer risk: results by tumour characteristics from a randomised trial. Br J Cancer 98(5):989–991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gallicchio L et al (2006) Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease. Cancer 106(7):1443–1452

    Article  CAS  PubMed  Google Scholar 

  24. Boyd NF et al (1992) Relationship between mammographic and histological risk factors for breast cancer. J Natl Cancer Inst 84(15):1170–1179

    Article  CAS  PubMed  Google Scholar 

  25. Yaffe M et al (1998) Breast cancer risk and measured mammographic density. Eur J Cancer Prev 7(Suppl 1):S47–S55

    Article  PubMed  Google Scholar 

  26. Boyd NF et al (1999) Mammographic densities and risk of breast cancer among subjects with a family history of this disease. J Natl Cancer Inst 91(16):1404–1408

    Article  CAS  PubMed  Google Scholar 

  27. Boyd NF et al (2001) Mammographic densities as a marker of human breast cancer risk and their use in chemoprevention. Curr Oncol Rep 3(4):314–321

    Article  CAS  PubMed  Google Scholar 

  28. Lam PB et al (2000) The association of increased weight, body mass index, and tissue density with the risk of breast carcinoma in Vermont. Cancer 89(2):369–375

    Article  CAS  PubMed  Google Scholar 

  29. Heine JJ, Malhotra P (2002) Mammographic tissue, breast cancer risk, serial image analysis, and digital mammography. Part 1. Tissue and related risk factors. Acad Radiol 9(3):298–316

    Article  PubMed  Google Scholar 

  30. Atkinson C et al (1999) Mammographic patterns as a predictive biomarker of breast cancer risk: effect of tamoxifen. Cancer Epidemiol Biomark Prev 8(10):863–866

    CAS  Google Scholar 

  31. Boyd NF et al (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 87(9):670–675

    Article  CAS  PubMed  Google Scholar 

  32. Harvey JA, Bovbjerg VE (2004) Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology 230(1):29–41

    Article  PubMed  Google Scholar 

  33. Warwick J et al (2003) Breast density and breast cancer risk factors in a high-risk population. Breast 12(1):10–16

    Article  CAS  PubMed  Google Scholar 

  34. Sala E et al (2000) High risk mammographic parenchymal patterns and diet: a case-control study. Br J Cancer 83(1):121–126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Konez O, Goyal M, Reaven RE (2001) Can tamoxifen cause a significant mammographic density change in breast parenchyma? Clin Imaging 25(5):303–308

    Article  CAS  PubMed  Google Scholar 

  36. Cuzick J et al (2011) Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. J Natl Cancer Inst 103(9):744–752

    Article  CAS  PubMed  Google Scholar 

  37. van Gils CH et al (1999) Changes in mammographic breast density and concomitant changes in breast cancer risk. Eur J Cancer Prev 8(6):509–515

    Article  PubMed  Google Scholar 

  38. Nyante SJ et al (2015) Prognostic significance of mammographic density change after initiation of tamoxifen for ER-positive breast cancer. J Natl Cancer Inst. doi:10.1093/jnci/dju425

    PubMed  PubMed Central  Google Scholar 

  39. Work ME et al (2014) Changes in mammographic density over time in breast cancer cases and women at high risk for breast cancer. Int J Cancer 135(7):1740–1744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ziv E et al (2004) Mammographic density and estrogen receptor status of breast cancer. Cancer Epidemiol Biomarkers Prev 13(12):2090–2095

    CAS  PubMed  Google Scholar 

  41. Maskarinec G et al (2008) Nonsteroidal anti-inflammatory drugs (NSAIDs) and mammographic density. Breast Cancer Res Treat 112(1):133–139

    Article  CAS  PubMed  Google Scholar 

  42. Stone J et al (2012) The association between mammographic density measures and aspirin or other NSAID use. Breast Cancer Res Treat 132(1):259–266

    Article  CAS  PubMed  Google Scholar 

  43. Terry MB et al (2008) Nonsteroidal anti-inflammatory drugs and change in mammographic density: a cohort study using pharmacy records on over 29,000 postmenopausal women. Cancer Epidemiol Biomarkers Prev 17(5):1088–1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. McTiernan A et al (2009) No effect of aspirin on mammographic density in a randomized controlled clinical trial. Cancer Epidemiol Biomarkers Prev 18(5):1524–1530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Balleyguier C et al (2007) BIRADS classification in mammography. Eur J Radiol 61(2):192–194

    Article  PubMed  Google Scholar 

  46. Kim S et al (2015) Lifetime use of nonsteroidal anti-inflammatory drugs and breast cancer risk: results from a prospective study of women with a sister with breast cancer. BMC Cancer 15:960

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sprague BL et al (2014) Prevalence of mammographically dense breasts in the United States. J Natl Cancer Inst. doi:10.1093/jnci/dju255

    Google Scholar 

  48. Boyd NF et al (2010) Breast tissue composition and susceptibility to breast cancer. J Natl Cancer Inst 102(16):1224–1237

    Article  PubMed  PubMed Central  Google Scholar 

  49. del Carmen MG et al (2007) Mammographic breast density and race. Am J Roentgenol 188(4):1147–1150

    Article  Google Scholar 

  50. Vachon CM et al (2000) Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control 11(7):653–662

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported in part by grants U54CA163313 and U54CA163303 from the National Cancer Institute.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Vermont School of Medicine, Burlington, VT, USA

    Marie E. Wood & Melissa Cuke

  2. Department of Surgery, University of Vermont School of Medicine, Burlington, VT, USA

    Brian L. Sprague

  3. Department of Radiology, Perelman School of MedicineUniversity of Pennsylvania, Philadelphia, PA, USA

    Andrew Oustimov, Emily F. Conant & Despina Kontos

  4. Department of Medicine, Perelman School of MedicineUniversity of Pennsylvania, Philadelphia, PA, USA

    Marie B. Synnstvedt

Authors
  1. Marie E. Wood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian L. Sprague
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrew Oustimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie B. Synnstvedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Melissa Cuke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emily F. Conant
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Despina Kontos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marie E. Wood.

Ethics declarations

Conflict of interest

E. Conant is a consultant for Hologic, Inc. Bedford, MA and Siemens’s Healthcare. The authors have no potential, perceived or actual conflict of interest to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wood, M.E., Sprague, B.L., Oustimov, A. et al. Aspirin use is associated with lower mammographic density in a large screening cohort. Breast Cancer Res Treat 162, 419–425 (2017). https://doi.org/10.1007/s10549-017-4127-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-017-4127-6

Keywords

Search

Navigation