Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 77, Issue 5, pp 895–903 | Cite as

The selective estrogen receptor modulators in breast cancer prevention

  • Fangxuan Li
  • Jinli Dou
  • Lijuan Wei
  • Shixia Li
  • Juntian LiuEmail author
Review Article

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.

Keywords

Selective estrogen receptor modulators Breast cancer Tamoxifen Raloxifene 

Notes

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).

Compliance with ethical standards

Conflict of interest

None.

References

  1. 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):227–228CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    DeSantis C et al (2014) Breast cancer statistics, 2013. CA Cancer J Clin 64(1):52–62CrossRefPubMedGoogle Scholar
  3. 3.
    Yager JD, Davidson NE (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med 354(3):270–282CrossRefPubMedGoogle Scholar
  4. 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):1–6CrossRefGoogle Scholar
  5. 5.
    Reimers L, Crew KD (2012) Tamoxifen versus raloxifene versus exemestane for chemoprevention. Curr Breast Cancer Rep 4(3):207–215CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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):1371–1388CrossRefPubMedGoogle Scholar
  7. 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):1652–1662CrossRefPubMedGoogle Scholar
  8. 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):160–165CrossRefPubMedGoogle Scholar
  9. 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):727–737CrossRefPubMedGoogle Scholar
  10. 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):98–101CrossRefPubMedGoogle Scholar
  11. 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):283–290CrossRefPubMedGoogle Scholar
  12. 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):272–282CrossRefPubMedGoogle Scholar
  13. 13.
    Cuzick J et al (2002) First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 360(9336):817–824CrossRefPubMedGoogle Scholar
  14. 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):67–75CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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):922–929CrossRefPubMedGoogle Scholar
  16. 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):2251–2256CrossRefPubMedGoogle Scholar
  17. 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):259–265CrossRefPubMedGoogle Scholar
  18. 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):327–334CrossRefPubMedGoogle Scholar
  19. 19.
    Phillips KA et al (2013) Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol 31(25):3091–3099CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Detterbeck F, Tanoue L, Reid A (2013) National comprehensive cancer network. J Natl Compr Canc Netw 11(4):365–366PubMedGoogle Scholar
  21. 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):499–502CrossRefPubMedGoogle Scholar
  22. 22.
    Advani P, Moreno-Aspitia A (2014) Current strategies for the prevention of breast cancer. Breast Cancer (Dove Med Press) 6:59–71Google Scholar
  23. 23.
    Cuzick J et al (2003) Overview of the main outcomes in breast-cancer prevention trials. Lancet 361(9354):296–300CrossRefPubMedGoogle Scholar
  24. 24.
    Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351(9114):1451–1467CrossRefGoogle Scholar
  25. 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 197–207Google Scholar
  26. 26.
    Decensi A et al (1998) Biologic activity of tamoxifen at low doses in healthy women. J Natl Cancer Inst 90(19):1461–1467CrossRefPubMedGoogle Scholar
  27. 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):779–790CrossRefPubMedGoogle Scholar
  28. 28.
    de Lima GR et al (2003) Effects of low dose tamoxifen on normal breast tissue from premenopausal women. Eur J Cancer 39(7):891–898CrossRefPubMedGoogle Scholar
  29. 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):4201–4209CrossRefPubMedGoogle Scholar
  30. 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 CrossRefPubMedGoogle Scholar
  31. 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):2753–2760CrossRefPubMedGoogle Scholar
  32. 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):284–286PubMedGoogle Scholar
  33. 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):9–16CrossRefPubMedGoogle Scholar
  34. 34.
    Hartmann LC et al (2015) A typical hyperplasia of the breast—risk assessment and management options. N Engl J Med 372(1):78–89CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Cykert S, Phifer N, Hansen C (2004) Tamoxifen for breast cancer prevention: a framework for clinical decisions. Obstet Gynecol 104(3):433–442CrossRefPubMedGoogle Scholar
  36. 36.
    Melnikow J et al (2006) Chemoprevention: drug pricing and mortality: the case of tamoxifen. Cancer 107(5):950–958CrossRefPubMedGoogle Scholar
  37. 37.
    Eckermann SD et al (2003) The benefits and costs of tamoxifen for breast cancer prevention. Aust N Z J Public Health 27(1):34–40CrossRefPubMedGoogle Scholar
  38. 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):281–290CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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):719–724PubMedGoogle Scholar
  40. 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):125–134CrossRefPubMedGoogle Scholar
  41. 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):1751–1761CrossRefPubMedGoogle Scholar
  42. 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):125–137CrossRefPubMedGoogle Scholar
  43. 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):2727–2741CrossRefPubMedGoogle Scholar
  44. 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):696–706CrossRefGoogle Scholar
  45. 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):996–1003PubMedGoogle Scholar
  46. 46.
    Cummings SR et al (2010) Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med 362(8):686–696CrossRefPubMedGoogle Scholar
  47. 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):1706–1715CrossRefPubMedGoogle Scholar
  48. 48.
    Cummings SR et al (2011) Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res 26(2):397–404CrossRefPubMedGoogle Scholar
  49. 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):299–306CrossRefPubMedGoogle Scholar
  50. 50.
    Ellis AJ et al (2015) Selective estrogen receptor modulators in clinical practice: a safety overview. Expert Opin Drug Saf 14(6):921–934CrossRefPubMedGoogle Scholar
  51. 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):610–620CrossRefPubMedPubMedCentralGoogle Scholar
  52. 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):351–363CrossRefPubMedGoogle Scholar
  53. 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):1827–1834CrossRefPubMedPubMedCentralGoogle Scholar
  54. 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):3235–3258CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bevers TB et al (2010) Breast cancer risk reduction. J Natl Compr Canc Netw 8(10):1112–1146PubMedGoogle Scholar
  56. 56.
    Waters EA et al (2012) Use of tamoxifen and raloxifene for breast cancer chemoprevention in 2010. Breast Cancer Res Treat 134(2):875–880CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Fangxuan Li
    • 1
  • Jinli Dou
    • 1
  • Lijuan Wei
    • 1
  • Shixia Li
    • 1
  • Juntian Liu
    • 1
    Email author
  1. 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 TherapyTianjin Medical University, Ministry of EducationTianjinChina

Personalised recommendations