Advertisement

Adjuvant Endocrine Therapy for Breast Cancer

  • Ibrahim Yildiz
  • Adnan Aydiner
Chapter

Abstract

Adjuvant endocrine therapy should be administered to patients with ER-positive and/or PR-positive invasive breast cancer, regardless of HER2 status, patient age, or cytotoxic therapy provided. Endocrine therapy can be initiated either with or after radiotherapy. Tamoxifen is the standard adjuvant endocrine therapy in women who are premenopausal at the time of diagnosis. Ovarian function suppression (OFS) might be added to tamoxifen in some patients younger than 35 years. In high-risk premenopausal patients with multiple poor prognostic factors, OFS plus an aromatase inhibitor (AI) may be a treatment option. The adjuvant tamoxifen treatment duration may be prolonged to 10 years in high-risk patients. In postmenopausal women, both tamoxifen and AIs may be valid endocrine therapy options. In high-risk postmenopausal patients with multiple poor prognostic factors, AI may be the best treatment option. An AI provided for a total of 5 or more years, an AI provided for 2–3 years followed by tamoxifen to complete 5 years of adjuvant endocrine therapy, and tamoxifen provided for 2–3 years followed by an AI to complete 5–8 years of endocrine therapy are all adjuvant treatment options. Tamoxifen for 4.5–6 years followed by 5 years of an AI or tamoxifen for up to 10 years is also an option. Extending AI treatment beyond 5 years in postmenopausal women can be recommended for high-risk patients.

Keywords

Adjuvant Endocrine therapy ER-positive PR-positive HER-2 positive HER-2 negative Aromatase inhibitor Tamoxifen Ovarian function supression LHRH agonists 

References

  1. 1.
    Osborne CK, Schiff R, Fuqua SA, Shou J. Estrogen receptor: current understanding of its activation and modulation. Clin Cancer Res. 2001;7:4338s–4342s; discussion 4411s–4412s.PubMedGoogle Scholar
  2. 2.
    Kumar R, Thompson EB. The structure of the nuclear hormone receptors. Steroids. 1999;64:310–9.CrossRefGoogle Scholar
  3. 3.
    Shou J, Massarweh S, Osborne CK, Wakeling AE, Ali S, Weiss H, et al. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J Natl Cancer Inst. 2004;96:926–35.CrossRefGoogle Scholar
  4. 4.
    Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351:1451–67.Google Scholar
  5. 5.
    Goldhirsch A, Ingle JN, Gelber RD, Coates AS, Thürlimann B, Senn HJ, Panel members. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009;20:1319–29.CrossRefGoogle Scholar
  6. 6.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52.CrossRefGoogle Scholar
  7. 7.
    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel members. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22:1736–47.CrossRefGoogle Scholar
  8. 8.
    Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98:10869–74.CrossRefGoogle Scholar
  9. 9.
    Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351:2817–26.CrossRefGoogle Scholar
  10. 10.
    van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347:1999–2009.CrossRefGoogle Scholar
  11. 11.
    Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.CrossRefGoogle Scholar
  12. 12.
    Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, et al. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol. 2009;27:3192–7.CrossRefGoogle Scholar
  13. 13.
    Bines J, Oleske DM, Cobleigh MA. Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol. 1996;14:1718–29.CrossRefGoogle Scholar
  14. 14.
    De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376:911–21.CrossRefGoogle Scholar
  15. 15.
    Torino F, Barnabei A, De Vecchis L, Appetecchia M, Strigari L, Corsello SM. Recognizing menopause in women with amenorrhea induced by cytotoxic chemotherapy for endocrine-responsive early breast cancer. Endocr Relat Cancer. 2012;19:R21–33.CrossRefGoogle Scholar
  16. 16.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, 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.CrossRefGoogle Scholar
  17. 17.
    Lonning PE. Evolution of endocrine adjuvant therapy for early breast cancer. Expert Opin Investig Drugs. 2010;19(Suppl 1):S19–30.CrossRefGoogle Scholar
  18. 18.
    Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst. 1996;88:1529–42.CrossRefGoogle Scholar
  19. 19.
    Stewart HJ, Forrest AP, Everington D, McDonald CC, Dewar JA, Hawkins RA, 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;74:297–9.CrossRefGoogle Scholar
  20. 20.
    Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, 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.CrossRefGoogle Scholar
  21. 21.
    Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Lonati V, Barni S. Five or more years of adjuvant endocrine therapy in breast cancer: a meta-analysis of published randomised trials. Breast Cancer Res Treat. 2013;140:233–40.CrossRefGoogle Scholar
  22. 22.
    Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008;26:1059–65.CrossRefGoogle Scholar
  23. 23.
    Regan MM, Leyland-Jones B, Bouzyk M, Pagani O, Tang W, Kammler R, 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;104:441–51.CrossRefGoogle Scholar
  24. 24.
    Rae JM, Drury S, Hayes DF, Stearns V, Thibert JN, Haynes BP, et al. CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012;104:452–60.CrossRefGoogle Scholar
  25. 25.
    LHRH-agonists in Early Breast Cancer Overview group, Cuzick J, Ambroisine L, Davidson N, Jakesz R, Kaufmann M, Regan M, 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;369:1711–23.CrossRefGoogle Scholar
  26. 26.
    Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Láng I, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371:107–18.CrossRefGoogle Scholar
  27. 27.
    Anderson WF, Chatterjee N, Ershler WB, Brawley OW. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res Treat. 2002;76:27–36.CrossRefGoogle Scholar
  28. 28.
    Dowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28:509–18.CrossRefGoogle Scholar
  29. 29.
    BIG 1-98 Collaborative Group, Mouridsen H, Giobbie-Hurder A, Goldhirsch A, Thürlimann B, Paridaens R, Smith I, et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009;361:766–76.CrossRefGoogle Scholar
  30. 30.
    Regan MM, Neven P, Giobbie-Hurder A, Goldhirsch A, Ejlertsen B, Mauriac L, 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;12:1101–8.CrossRefGoogle Scholar
  31. 31.
    van de Velde CJ, Rea D, Seynaeve C, Putter H, Hasenburg A, Vannetzel JM, et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011;377:321–31.CrossRefGoogle Scholar
  32. 32.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386:1341–52.CrossRefGoogle Scholar
  33. 33.
    Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377(19):1836–46.CrossRefGoogle Scholar
  34. 34.
    Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, 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;97:1262–71.CrossRefGoogle Scholar
  35. 35.
    Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. 2016;375(3):209–19.CrossRefGoogle Scholar
  36. 36.
    Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E, et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007;99:1845–53.CrossRefGoogle Scholar
  37. 37.
    Mamounas EP, Jeong JH, Wickerham DL, Smith RE, Ganz PA, Land SR, et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008;26:1965–71.CrossRefGoogle Scholar
  38. 38.
    Mamounas EP, Bandos H, Lembersky BC. A randomized, double-blinded, placebo-controlled clinical trial of extended adjuvant endocrine therapy (tx) with letrozole (L) in postmenopausal women with hormone-receptor (+) breast cancer (BC) who have completed previous adjuvant tx with an aromatase inhibitor (AI): results from NRG Oncology/NSABP B-42. In: Presented at: 2016 San Antonio breast cancer symposium; December 6–10; San Antonio, TX, 2016.Google Scholar
  39. 39.
    Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM, Swinkels ACP, Smorenburg CH, van der Sangen MJC, Dutch Breast Cancer Research Group (BOOG) for the DATA Investigators, et al. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017;18:1502–11.CrossRefGoogle Scholar
  40. 40.
    Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, Putter H, van den Bosch J, et al. IDEAL Study Group. Optimal duration of extended adjuvant endocrine therapy for early breast cancer; results of the IDEAL trial (BOOG 2006-05). J Natl Cancer Inst. 2018;110(1).  https://doi.org/10.1093/jnci/djx134.CrossRefGoogle Scholar
  41. 41.
    Goldvaser H, AlGorashi I, Ribnikar D, Seruga B, Templeton AJ, Ocana A, et al. Efficacy of extended adjuvant therapy with aromatase inhibitors in early breast cancer among common clinicopathologically-defined subgroups: a systematic review and meta-analysis. Cancer Treat Rev. 2017;60:53–9.CrossRefGoogle Scholar
  42. 42.
    Colleoni M, Luo W, Karlsson P, Chirgwin J, Aebi S, Jerusalem G, SOLE Investigators, et al. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19:127.CrossRefGoogle Scholar
  43. 43.
    Viale G, Regan MM, Dell’Orto P, Mastropasqua MG, Maiorano E, Rasmussen BB, et al. Which patients benefit most from adjuvant aromatase inhibitors? Results using a composite measure of prognostic risk in the BIG 1-98 randomized trial. Ann Oncol. 2011;22:2201–7.CrossRefGoogle Scholar
  44. 44.
    Dowsett M, Nielsen TO, A’Hern R, Bartlett J, Coombes RC, Cuzick J, et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst. 2011;103:1656–64.CrossRefGoogle Scholar
  45. 45.
    Dowsett M, Smith IE, Ebbs SR, Dixon JM, Skene A, A'Hern R, et al. Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer. J Natl Cancer Inst. 2007;99:167–70.CrossRefGoogle Scholar
  46. 46.
    Geisler J, Haynes B, Anker G, Dowsett M, Lønning PE. Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study. J Clin Oncol. 2002;20:751–7.CrossRefGoogle Scholar
  47. 47.
    Dixon JM, Renshaw L, Young O, Murray J, Macaskill EJ, McHugh M, et al. Letrozole suppresses plasma estradiol and estrone sulphate more completely than anastrozole in postmenopausal women with breast cancer. J Clin Oncol. 2008;26:1671–6.CrossRefGoogle Scholar
  48. 48.
    Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol. 2011;29:2342–9.CrossRefGoogle Scholar
  49. 49.
    Curigliano G, Burstein HJ, Winer EP, Gnant M, Dubsky P, Loibl S, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017;28:1700–12.CrossRefGoogle Scholar
  50. 50.
    Henry NL, Azzouz F, Desta Z, Li L, Nguyen AT, Lemler S, et al. Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer. J Clin Oncol. 2012;30:936–42.CrossRefGoogle Scholar
  51. 51.
    Aydiner A. Meta-analysis of breast cancer outcome and toxicity in adjuvant trials of aromatase inhibitors in postmenopausal women. Breast. 2013;22:121–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ibrahim Yildiz
    • 1
  • Adnan Aydiner
    • 2
  1. 1.Internal Medicine, Department of Medical Oncology, Acibadem HospitalIstanbulTurkey
  2. 2.Internal Medicine, Medical Oncology, Istanbul Medical Faculty, Department of Medical Oncology, Institute of OncologyIstanbul UniversityIstanbulTurkey

Personalised recommendations