Skip to main content

Advertisement

Log in

Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women

  • Breast Cancer (ML Telli, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients’ preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

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

  1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC Cancer Base no. 11. Lyon: International Agency for Research on Cancer; 2013.

    Google Scholar 

  2. Assi HA, Khoury KE, Dbouk H, et al. Epidemiology and prognosis of breast cancer in young women. J Thorac Dis. 2013;5(Suppl 1):S2–8.

    PubMed  PubMed Central  Google Scholar 

  3. Anderson WF, Chatterjee N, Ershler WB, et al. Estrogen receptor breast cancer phenotypes in the surveillance, epidemiology, and end results database. Breast Cancer Res Treat. 2002;76:27–36.

    Article  CAS  PubMed  Google Scholar 

  4. Anders CK, Hsu DS, Broadwater G, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26:3324–30.

    Article  PubMed  Google Scholar 

  5. Rock CL, Doyle C, Demark-Wahnefried W, et al. Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin. 2012;62(4):243–74.

    Article  PubMed  Google Scholar 

  6. Protani M, Coory M, Martin JH. Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat. 2010;123(3):627–35.

    Article  PubMed  Google Scholar 

  7. Ewertz M, Jensen MB, Gunnarsdóttir KA, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol. 2011;29(1):25–31.

    Article  PubMed  Google Scholar 

  8. Nichols HB, Trentham-Dietz A, Egan KM, et al. Body mass index before and after breast cancer diagnosis: associations with all-cause, breast cancer, and cardiovascular disease mortality. Cancer Epidemiol Biomark Prev. 2009;18(5):1403–9.

    Article  Google Scholar 

  9. Pfeiler G, Königsberg R, Fesl C, et al. Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. J Clin Oncol. 2011;29(19):2653–9.

    Article  CAS  PubMed  Google Scholar 

  10. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington DC: AICR; 2007.

    Google Scholar 

  11. Magné N, Melis A, Chargari C, et al. Recommendations for a lifestyle which could prevent breast cancer and its relapse: physical activity and dietetic aspects. Crit Rev Oncol Hematol. 2011;80:450–9.

    Article  PubMed  Google Scholar 

  12. Renehan AG, Zwahlen M, Minder C, et al. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363:1346–53.

    Article  CAS  PubMed  Google Scholar 

  13. Kushi ES, Holly JM, Pollak MN, et al. Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk. Cancer Epidemiol Biomark Prev. 2005;14:699–704.

    Article  Google Scholar 

  14. Fong DY, Ho JW, Hui BP, et al. Physical activity for cancer survivors: meta-analysis of randomised controlled trials. BMJ. 2012;344:e70.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Kushi LH, Doyle C, McCullough M, et al. For the American Cancer Society 2010 Nutrition and Physical Activity Guidelines Advisory Committee. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012;62(1):30–67.

    Article  PubMed  Google Scholar 

  16. Mishra SI, Scherer RW, Geigle PM, et al. Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev. 2012;8:CD007566.

    Google Scholar 

  17. Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2012;11:CD006145.

    PubMed  Google Scholar 

  18. Hayes SC, Rye S, Disipio T, et al. Exercise for health: a randomized, controlled trial evaluating the impact of a pragmatic, translational exercise intervention on the quality of life, function and treatment-related side effects following breast cancer. Breast Cancer Res Treat. 2012;137(1):175–86.

    Article  PubMed  Google Scholar 

  19. Kwan ML, Cohn JC, Armer JM, Stewart BR, Cormier JN. Exercise in patients with lymphedema: a systematic review of the contemporary literature. J Cancer Surviv. 2011;5(4):320–36.

    Article  PubMed  Google Scholar 

  20. Pierce JP, Patterson RE, Senger CM, et al. Lifetime cigarette smoking and breast cancer prognosis in the after breast cancer pooling project. J Natl Cancer Inst. 2014;106(1):djt359.

    Article  PubMed  Google Scholar 

  21. Osborne CK. Steroid hormoner receptors in breast cancer management. Breast Cancer Res Treat. 1998;51:227–38.

    Article  CAS  PubMed  Google Scholar 

  22. Early Breast Cancer Trialists’Collaborative Group (EBCTG). Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet. 1998;352:930–42.

    Article  Google Scholar 

  23. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, 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;378:771–84.

    Article  Google Scholar 

  24. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), et al. Lancet. 2005;365:1687–717.

    Article  Google Scholar 

  25. Sacco K, Grech G. Actionable pharmacogenetic markers for prediction and prognosis in breast cancer. EPMA J. 2015;6(1):15–20.

    Article  PubMed  PubMed Central  Google Scholar 

  26. •• Davies C, Pan H, Godwin J, 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. This practice-changing trial showed that extending tamoxifen adjuvant therapy from 5 to 10 years in women with ER+ disease further reduced recurrence and mortality

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. •• Gray RG, Rea D, Handley K, et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol 2013; 31(suppl): abstr 5. As much as the ATLAS trial, the aTTOm trial is one of the most important studies that redefined the optimal duration of adjuvant therapy with Tamoxifen in specific groups of patients.

  28. Gnant M, Thomssen C, Harbeck N. St. Gallen/Vienna 2015: a brief summary of the consensus discussion. Breast Care (Basel). 2015a;10(2):124–30.

    Article  Google Scholar 

  29. • LHRH-agonists in Early Breast Cancer Overview group. 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;369:1711–23. This is a large meta-analysis that collected data from 11,906 patients included in 16 trials. The interpretation of these data showed that the ovarian suppression with LHRH-agonists can provide a beneficial trend in terms of recurrence and DFS in premenopausal women with ER+disease

    Article  Google Scholar 

  30. Christinat A, Di Lascio S, Pagani O. Hormonal therapies in young breast cancer patients: when, what and for how long? J Thorac Dis. 2013;5(suppl 1):S36–46.

    PubMed  PubMed Central  Google Scholar 

  31. Pagani O, O’Neill A, Castiglione M, et al. Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial IV. Eur J Cancer. 1998;34:632–40.

    Article  CAS  PubMed  Google Scholar 

  32. Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol. 2006;24:5769–79.

    Article  CAS  PubMed  Google Scholar 

  33. • Rossi L, Pagani O. Impact on Breast Cancer Treatment on Fertility. In: Biglia N, Peccatori FA. Breast Cancer Fertility Preservation and Reproduction. Springer, 2015. DOI: 10.1007/978-3-19-17278-1_3.In this chapter it is thoroughy analyzed the impact of endocrine, cytotoxic and biological therapies on fertility in light of the recent literature.

  34. Masuda N, Iwata H, Rai Y, et al. Monthly versus 3-monthly goserelin acetate treatment in pre-menopausal patients with estrogen receptor-positive early breast cancer. Breast Cancer Res Treat. 2011;126(2):443–51.

    Article  CAS  PubMed  Google Scholar 

  35. Paluch-Shimon S, Pagani O, Partridge AH, et al. Second international consensus guidelines for breast cancer in young women (BCY2). Breast. 2016;26:87–99.

    Article  PubMed  Google Scholar 

  36. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. J Clin Oncol. 2016;34:1689–701.

    Article  CAS  PubMed  Google Scholar 

  37. Senkus E, Kyriakides S, Ohno S, et al. Primary breast cancer: ESMO clinical practice guidelines. Ann Oncol. 2015;26(suppl 5):v8–v30.

    Article  PubMed  Google Scholar 

  38. Dowsett M, Folkerd E, Doody D, et al. The biology of steroid hormones and endocrine treatment of breast cancer. Breast. 2005;14:452–7.

    Article  PubMed  Google Scholar 

  39. Bernhard J, Luo W, Ribi K, et al. Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. Lancet Oncol. 2015;16(7):848–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hackshaw A, Baum M, Fornander T, et al. Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst. 2009;101(5):341–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Goel S, Sharma R, Hamilton A, Beith J. LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women. Cochrane Database Syst Rev. Issue 4: CD004562. 2009. DOI: 10.1002/14651858.CD004562.pub4.

  42. • Yan S, Li K, Jiao X, et al. Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials. Onco Targets Ther. 2015;12(8):1433–41. This is a comprehensive meta-analysis that evaluates the addition of ovarian function suppression to adjuvant tamoxifen in premenopausal patients

    Article  Google Scholar 

  43. •• Francis P, Meredith M, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372:436–46. This is a large international trial that provided solid data for the addition of ovarian function suppression to adjuvant hormonal therapy to reduce the risk of recurrence in premenopausal women with ER+ disease at high enough risk to be treated with chemotherapy

    Article  PubMed  Google Scholar 

  44. •• Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371:107–18. Planned to be complementary to the SOFT study, this trial demonstrates that ovarian suppression plus exemestane is an effective adjuvant therapy in young women with ER+ disease. TEXT and SOFT trials are, at present, the most important trials about the association between ovarian suppression, tamoxifen or aromatase inhibitors in premenopausal patient with early ER+ breast cancer

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gnant M, Mlineritsch B, Stoeger H, Austrian Breast and Colorectal Cancer Study Group, et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015b;26(2):313–20.

    Article  CAS  PubMed  Google Scholar 

  46. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015;26:1533–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hershman DL, Shao T, Kushi LH, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat. 2011;126:529–37.

    Article  CAS  PubMed  Google Scholar 

  48. Murphy CC, Bartholomew LK, Carpentier MY, et al. Adherence to adjuvant hormonal therapy among breast cancer survivors in clinical practice: a systematic review. Breast Cancer Res Treat. 2012;134:459–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Llarena NC, Estevez SL, Tucker SL, et al. Impact of fertility concerns on tamoxifen intitation and persistence. J Natl Cancer Inst. 2015; 107(10).

  50. Runowicz CD, Leach CR, Henry NL, et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34(6):611–35.

    Article  CAS  PubMed  Google Scholar 

  51. Azim Jr HA, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–9.

    Article  PubMed  Google Scholar 

  52. Asiri MA, Tunio MA, Abdulmoniem R. Is radiation-induced ovarian ablation in breast cancer an obsolete procedure? Results of a meta-analysis. Breast Cancer. 2016;8:109–16.

    PubMed  PubMed Central  Google Scholar 

  53. Schmidberger H, Hermann RM, Hess CF, et al. Interactions between radiation and endocrine therapy in breast cancer. Endocr Relat Cancer. 2003;10(3):375–88.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olivia Pagani MD.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

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

Additional information

This article is part of the Topical Collection on Breast Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rossi, L., Pagani, O. Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women. Curr. Treat. Options in Oncol. 18, 28 (2017). https://doi.org/10.1007/s11864-017-0473-1

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-017-0473-1

Keywords

Navigation