Skip to main content

Advertisement

Springer Nature Link
Log in

The selective estrogen receptor modulators in breast cancer prevention

  • Review Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Backgrounds

Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER).

Methods

Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention.

Results

To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low.

Conclusion

A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Mandelblatt JS, Tosteson AN, van Ravesteyn NT (2013) Costs, evidence, and value in the Medicare program: the challenges of technology innovation in breast cancer prevention and control. JAMA Intern Med 173(3):227–228

    Article  PubMed  PubMed Central  Google Scholar 

  2. DeSantis C et al (2014) Breast cancer statistics, 2013. CA Cancer J Clin 64(1):52–62

    Article  PubMed  Google Scholar 

  3. Yager JD, Davidson NE (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med 354(3):270–282

    Article  CAS  PubMed  Google Scholar 

  4. Garcia-Closas M, Gunsoy NB, Chatterjee N (2014) Combined associations of genetic and environmental risk factors: implications for prevention of breast cancer. J Natl Cancer Inst 106(11):1–6

    Article  Google Scholar 

  5. Reimers L, Crew KD (2012) Tamoxifen versus raloxifene versus exemestane for chemoprevention. Curr Breast Cancer Rep 4(3):207–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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 

  7. Fisher B et al (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97(22):1652–1662

    Article  CAS  PubMed  Google Scholar 

  8. Veronesi U et al (2003) Italian randomized trial among women with hysterectomy: tamoxifen and hormone-dependent breast cancer in high-risk women. J Natl Cancer Inst 95(2):160–165

    Article  CAS  PubMed  Google Scholar 

  9. Veronesi U et al (2007) Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy. J Natl Cancer Inst 99(9):727–737

    Article  CAS  PubMed  Google Scholar 

  10. Powles T et al (1998) Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352(9122):98–101

    Article  CAS  PubMed  Google Scholar 

  11. Powles TJ et al (2007) Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 99(4):283–290

    Article  CAS  PubMed  Google Scholar 

  12. Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A (2007) Long-term results of tamoxifen prophylaxis for breast cancer—96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 99(4):272–282

    Article  CAS  PubMed  Google Scholar 

  13. Cuzick J et al (2002) First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 360(9336):817–824

    Article  CAS  PubMed  Google Scholar 

  14. Cuzick J et al (2015) Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol 16(1):67–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Malone KE et al (1998) BRCA1 mutations and breast cancer in the general population: analyses in women before age 35 years and in women before age 45 years with first-degree family history. JAMA 279(12):922–929

    Article  CAS  PubMed  Google Scholar 

  16. King MC et al (2001) Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286(18):2251–2256

    Article  CAS  PubMed  Google Scholar 

  17. Kote-Jarai Z et al (2007) BRCA1/BRCA2 mutation status and analysis of cancer family history in participants of the Royal Marsden Hospital tamoxifen chemoprevention trial. Cancer Lett 247(2):259–265

    Article  CAS  PubMed  Google Scholar 

  18. Xu L et al (2015) Tamoxifen and risk of contralateral breast cancer among women with inherited mutations in BRCA1 and BRCA2: a meta-analysis. Breast Cancer 22(4):327–334

    Article  CAS  PubMed  Google Scholar 

  19. Phillips KA et al (2013) Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol 31(25):3091–3099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Detterbeck F, Tanoue L, Reid A (2013) National comprehensive cancer network. J Natl Compr Canc Netw 11(4):365–366

    PubMed  Google Scholar 

  21. Phillips KA, Lindeman GJ (2014) Breast cancer prevention for BRCA1 and BRCA2 mutation carriers: Is there a role for tamoxifen? Future Oncol 10(4):499–502

    Article  CAS  PubMed  Google Scholar 

  22. Advani P, Moreno-Aspitia A (2014) Current strategies for the prevention of breast cancer. Breast Cancer (Dove Med Press) 6:59–71

    CAS  Google Scholar 

  23. Cuzick J et al (2003) Overview of the main outcomes in breast-cancer prevention trials. Lancet 361(9354):296–300

    Article  CAS  PubMed  Google Scholar 

  24. Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351(9114):1451–1467

    Article  Google Scholar 

  25. Maltoni C et al (1996) Experimental results on the chemopreventive and side effects of tamoxifen using a human-equivalent animal model. In: Maltoni C, Soffritti M, Davis W (eds) The scientific bases of cancer chemoprevention. Elsevier Science BV, Amsterdam, pp 197–207

    Google Scholar 

  26. Decensi A et al (1998) Biologic activity of tamoxifen at low doses in healthy women. J Natl Cancer Inst 90(19):1461–1467

    Article  CAS  PubMed  Google Scholar 

  27. Decensi A et al (2003) A randomized trial of low-dose tamoxifen on breast cancer proliferation and blood estrogenic biomarkers. J Natl Cancer Inst 95(11):779–790

    Article  CAS  PubMed  Google Scholar 

  28. de Lima GR et al (2003) Effects of low dose tamoxifen on normal breast tissue from premenopausal women. Eur J Cancer 39(7):891–898

    Article  PubMed  Google Scholar 

  29. Decensi A et al (2007) Randomized dose-ranging trial of tamoxifen at low doses in hormone replacement therapy users. J Clin Oncol 25(27):4201–4209

    Article  CAS  PubMed  Google Scholar 

  30. Decensi A, Galli A, Veronesi U (2003) HRT opposed to low-dose tamoxifen (HOT study): rationale and design. Recent Results Cancer Res 163:104–111 discussion 264-6

    Article  CAS  PubMed  Google Scholar 

  31. DeCensi A et al (2013) A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study. Ann Oncol 24(11):2753–2760

    Article  CAS  PubMed  Google Scholar 

  32. Smith TJ, Hillner BE (2000) Tamoxifen should be cost-effective in reducing breast cancer risk in high-risk women. J Clin Oncol 18(2):284–286

    CAS  PubMed  Google Scholar 

  33. Hershman D et al (2002) Outcomes of tamoxifen chemoprevention for breast cancer in very high-risk women: a cost-effectiveness analysis. J Clin Oncol 20(1):9–16

    Article  CAS  PubMed  Google Scholar 

  34. Hartmann LC et al (2015) A typical hyperplasia of the breast—risk assessment and management options. N Engl J Med 372(1):78–89

    Article  PubMed  PubMed Central  Google Scholar 

  35. Cykert S, Phifer N, Hansen C (2004) Tamoxifen for breast cancer prevention: a framework for clinical decisions. Obstet Gynecol 104(3):433–442

    Article  CAS  PubMed  Google Scholar 

  36. Melnikow J et al (2006) Chemoprevention: drug pricing and mortality: the case of tamoxifen. Cancer 107(5):950–958

    Article  PubMed  Google Scholar 

  37. Eckermann SD et al (2003) The benefits and costs of tamoxifen for breast cancer prevention. Aust N Z J Public Health 27(1):34–40

    Article  PubMed  Google Scholar 

  38. Kondo M, Hoshi SL, Toi M (2009) Economic evaluation of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan. Br J Cancer 100(2):281–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bevers TB (2007) The STAR trial: evidence for raloxifene as a breast cancer risk reduction agent for postmenopausal women. J Natl Compr Canc Netw 5(8):719–724

    PubMed  Google Scholar 

  40. Cauley JA et al (2001) Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 65(2):125–134

    Article  CAS  PubMed  Google Scholar 

  41. Martino S et al (2004) Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 96(23):1751–1761

    Article  CAS  PubMed  Google Scholar 

  42. Barrett-Connor E et al (2006) Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med 355(2):125–137

    Article  CAS  PubMed  Google Scholar 

  43. Vogel VG et al (2006) Effects of tamoxifen versus raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295(23):2727–2741

    Article  CAS  PubMed  Google Scholar 

  44. Vogel VG et al (2010) Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila) 3(6):696–706

    Article  CAS  Google Scholar 

  45. Armstrong K et al (2001) Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk. Obstet Gynecol 98(6):996–1003

    CAS  PubMed  Google Scholar 

  46. Cummings SR et al (2010) Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med 362(8):686–696

    Article  CAS  PubMed  Google Scholar 

  47. LaCroix AZ et al (2010) Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst 102(22):1706–1715

    Article  CAS  PubMed  Google Scholar 

  48. Cummings SR et al (2011) Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res 26(2):397–404

    Article  CAS  PubMed  Google Scholar 

  49. Powles TJ et al (2012) Breast cancer incidence in postmenopausal women with osteoporosis or low bone mass using arzoxifene. Breast Cancer Res Treat 134(1):299–306

    Article  CAS  PubMed  Google Scholar 

  50. Ellis AJ et al (2015) Selective estrogen receptor modulators in clinical practice: a safety overview. Expert Opin Drug Saf 14(6):921–934

    Article  CAS  PubMed  Google Scholar 

  51. Lewis-Wambi JS et al (2011) The selective estrogen receptor modulator bazedoxifene inhibits hormone-independent breast cancer cell growth and down-regulates estrogen receptor alpha and cyclin D1. Mol Pharmacol 80(4):610–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Silverman SL et al (2012) Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study. Osteoporos Int 23(1):351–363

    Article  CAS  PubMed  Google Scholar 

  53. Cuzick J et al (2013) Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet 381(9880):1827–1834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Visvanathan K et al (2009) American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol 27(19):3235–3258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bevers TB et al (2010) Breast cancer risk reduction. J Natl Compr Canc Netw 8(10):1112–1146

    CAS  PubMed  Google Scholar 

  56. Waters EA et al (2012) Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010. Breast Cancer Res Treat 134(2):875–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported partially by the Tianjin Natural Science Funds (13JCQNJC12700), Tianjin Medical University Natural Science Funds (2013KY02), and National Natural Science Fund of China (81502309).

Author information

Author notes

    Authors and Affiliations

    1. Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Huanhuxi Road, Hexi District, Tianjin, 300060, China

      Fangxuan Li, Jinli Dou, Lijuan Wei, Shixia Li & Juntian Liu

    Authors
    1. Fangxuan Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jinli Dou
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Lijuan Wei
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Shixia Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Juntian Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Juntian Liu.

    Ethics declarations

    Conflict of interest

    None.

    Additional information

    Fangxuan Li and Jinli Dou have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Li, F., Dou, J., Wei, L. et al. The selective estrogen receptor modulators in breast cancer prevention. Cancer Chemother Pharmacol 77, 895–903 (2016). https://doi.org/10.1007/s00280-016-2959-0

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00280-016-2959-0

    Keywords

    Search

    Navigation