Skip to main content
SpringerLink
Log in

Adjuvant Therapy for Breast Cancer: Hormonal Therapy

  • Chapter
  • First Online:
Breast Disease

  • 2252 Accesses

Abstract

Approximately two-thirds of patients diagnosed with early-stage breast cancer have hormone-sensitive disease (estrogen receptor [ER]-positive and/or progesterone receptor [PR]-positive), and as a result, adjuvant endocrine therapy plays a critical role in reducing the risk of recurrence and improving survival. Data generated from clinical trials over the last 30 years has definitively demonstrated the positive impact of adjuvant endocrine therapy, first with the use of tamoxifen and more recently with the use of aromatase inhibitors either as monotherapy or in sequence with tamoxifen. Many issues need to be understood when considering the optimal approach for adjuvant endocrine therapy in an individual patient, both in terms of optimizing risk reduction and maintaining quality of life. The following discussion will summarize the current state of the art in 2013 and also highlight unresolved research issues of clinical importance.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 189.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351(9114):1451–67.

    Google Scholar 

  2. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. An overview of 61 randomized trials among 28,896 women. Early Breast Cancer Trialists’ Collaborative Group. N Engl J Med. 1988;319(26):1681–92.

    Google Scholar 

  3. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1992;339(8785):71–85.

    Google Scholar 

  4. Dowsett M, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28(3):509–18.

    Article  CAS  PubMed  Google Scholar 

  5. Early Breast Cancer Trialists’ Collaborative Group, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–84.

    Article  Google Scholar 

  6. Stewart HJ, Prescott RJ, Forrest AP. Scottish adjuvant tamoxifen trial: a randomized study updated to 15 years. J Natl Cancer Inst. 2001;93(6):456–62.

    Article  CAS  PubMed  Google Scholar 

  7. Stewart HJ, et al. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group. Br J Cancer. 1996;74(2):297–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Davies C, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381:805–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Earl H, et al. The optimal duration of adjuvant tamoxifen treatment for breast cancer remains uncertain: randomize into aTTom. Clin Oncol. 1997;9(3):141–3.

    Article  CAS  Google Scholar 

  10. Day R, et al. Health-related quality of life and tamoxifen in breast cancer prevention: a report from the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Clin Oncol. 1999;17(9):2659–69.

    CAS  PubMed  Google Scholar 

  11. Fisher B, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 1998;90(18):1371–88.

    Article  CAS  PubMed  Google Scholar 

  12. Goetz MP. Tamoxifen, endoxifen, and CYP2D6: the rules for evaluating a predictive factor. Oncology (Williston Park). 2009;23(14):1233–4, 1236.

    Google Scholar 

  13. Hoskins JM, Carey LA, McLeod HL. CYP2D6 and tamoxifen: DNA matters in breast cancer. Nat Rev Cancer. 2009;9(8):576–86.

    Article  CAS  PubMed  Google Scholar 

  14. Rae JM, et al. CYP2D6 genotype and tamoxifen response. Breast Cancer Res. 2005;7(5):E6.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Regan MM, et al. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst. 2012;104(6):441–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Rae JM, et al. CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012;104(6):452–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. NCCN.org. NCCN clinical practice guidelines in oncology: breast cancer version 2.2013, 2013.

    Google Scholar 

  18. Higgins MJ, et al. Pharmacogenetics of tamoxifen: who should undergo CYP2D6 genetic testing? J Natl Compr Canc Netw. 2009;7(2):203–13.

    CAS  PubMed  Google Scholar 

  19. Burstein HJ, et al. American society of clinical oncology clinical practice guideline update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Oncol Pract. 2010;6(5):243–6.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Santen RJ, Harvey HA. Use of aromatase inhibitors in breast carcinoma. Endocr Relat Cancer. 1999;6(1):75–92.

    Article  CAS  PubMed  Google Scholar 

  21. Osborne CK. Aromatase inhibitors in relation to other forms of endocrine therapy for breast cancer. Endocr Relat Cancer. 1999;6(2):271–6.

    Article  CAS  PubMed  Google Scholar 

  22. Amir E, et al. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299–309.

    Article  CAS  PubMed  Google Scholar 

  23. ATAC Trialists’ Study Group, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9(1):45–53.

    Article  Google Scholar 

  24. Baum M, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359(9324):2131–9.

    Article  CAS  PubMed  Google Scholar 

  25. BIG 1-98 Collaborative Group, et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009;361(8):766–76.

    Article  Google Scholar 

  26. Breast International Group 1-98 Collaborative Group, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353(26):2747–57.

    Article  Google Scholar 

  27. Regan MM, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol. 2011;12(12):1101–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Coombes RC, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007;369(9561):559–70.

    Article  CAS  PubMed  Google Scholar 

  29. Coombes RC, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350(11):1081–92.

    Article  CAS  PubMed  Google Scholar 

  30. Boccardo F, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: long term results of the Italian Tamoxifen Anastrozole trial. Eur J Cancer. 2013;49:1546–1554.

    Article  PubMed  Google Scholar 

  31. Boccardo F, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer. Updated results of the Italian Tamoxifen Anastrozole (ITA) trial. Ann Oncol. 2006;17 Suppl 7:vii10–4.

    PubMed  Google Scholar 

  32. Jakesz R, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366(9484):455–62.

    Article  CAS  PubMed  Google Scholar 

  33. Jonat W, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. Lancet Oncol. 2006;7(12):991–6.

    Article  CAS  PubMed  Google Scholar 

  34. Goss PE, et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol. 2008;26(12):1948–55.

    Article  CAS  PubMed  Google Scholar 

  35. Goss PE, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005;97(17):1262–71.

    Article  CAS  PubMed  Google Scholar 

  36. Goss PE, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349(19):1793–802.

    Article  CAS  PubMed  Google Scholar 

  37. Folkerd EJ, et al. Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. J Clin Oncol. 2012;30(24):2977–80.

    Article  CAS  PubMed  Google Scholar 

  38. Dixon JM, et al. Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol. 2008;26(10):1671–6.

    Article  CAS  PubMed  Google Scholar 

  39. Sestak I, et al. Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol. 2008;9(9):866–72.

    Article  PubMed  Google Scholar 

  40. Crew KD, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007;25(25):3877–83.

    Article  PubMed  Google Scholar 

  41. Hadji P. Breast cancer: aromatase inhibitors–bone health assessment is crucial. Natl Rev Clin Oncol. 2012;9(5):254–5.

    Article  CAS  Google Scholar 

  42. Hadji P. Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol. 2009;69(1):73–82.

    Article  PubMed  Google Scholar 

  43. Hadji P, et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol. 2008;19(8):1407–16.

    Article  CAS  PubMed  Google Scholar 

  44. Clunie GP, et al. Evaluating bone health in women with oestrogen receptor positive breast cancer (ERBC) starting aromatase inhibitors. Eur J Surg Oncol. 2009;35(5):475–80.

    Article  CAS  PubMed  Google Scholar 

  45. LHRH-agonists in Early Breast Cancer Overview group, et al. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet. 2007;369(9574):1711–23.

    Article  Google Scholar 

  46. Jonat W. Luteinizing hormone-releasing hormone analogues–the rationale for adjuvant use in premenopausal women with early breast cancer. Br J Cancer. 1998;78 Suppl 4:5–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Robertson JF, et al. Combined endocrine effects of LHRH agonist (Zoladex) and tamoxifen (Nolvadex) therapy in premenopausal women with breast cancer. Br J Surg. 1989;76(12):1262–5.

    Article  CAS  PubMed  Google Scholar 

  48. Love RR. Adjuvant hormonal therapy in premenopausal women with operable breast cancer: not-so-peripheral perspectives. Oncology (Williston Park). 2010;24(4):322–7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medicine – Division of Hematology/Oncology, Maggie Daley Center for Women’s Cancer Care, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine at Northwestern Memorial Hospital, 676 North St. Clair, Suite 850, Chicago, IL, 60611, USA

    William J. Gradishar MD

Authors
  1. William J. Gradishar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William J. Gradishar MD .

Editor information

Editors and Affiliations

  1. Advocate Center for Breast Health, Advocate Cancer Institute, Oak Lawn, Illinois, USA

    Adam I. Riker

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gradishar, W.J. (2015). Adjuvant Therapy for Breast Cancer: Hormonal Therapy. In: Riker, A. (eds) Breast Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1145-5_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1145-5_24

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1144-8

  • Online ISBN: 978-1-4939-1145-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation