Skip to main content
SpringerLink
Log in

Sequential Hormonal Therapy for Metastatic Breast Cancer after Adjuvant Tamoxifen or Anastrozole

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Margolese RG, Fisher B, Hortobagyi GN, Bloomer WD: Neoplasms of the breast. 5: 1735-1822, 2000

    Google Scholar 

  2. Early Breast Cancer Trialists' Collaborative Group: Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351: 1451-1467, 1998

    Google Scholar 

  3. Early Breast Cancer Trialists' Collaborative Group: Ovarian ablation for early breast cancer. Cochrane Database Syst Rev 3: CD000485, 2000

    Google Scholar 

  4. The Nolvadex Adjuvant Trial Organisation: Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer. Analysis at six years. Lancet 1: 836-840, 1985

    Google Scholar 

  5. Scottish Cancer Trials Breast Group and ICRF Breast Unit GHL: Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Lancet 341: 1293-1298, 1993

    Google Scholar 

  6. Early Breast Cancer Trialists' Collaborative Group: Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet 348: 1189-1196, 1996

    Google Scholar 

  7. Boccardo F, Rubagotti A, Amoroso D, Mesiti M, Romeo D, Sismondi P, Giai M, Genta F, Pacini P, Distante V, Bolognesi A, Aldrighetti D, Farris A: Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptorpositive pre-/perimenopausal breast cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. J Clin Oncol 18: 2718-2727, 2000

    Google Scholar 

  8. Jakesz R, Hausmaninger H, Kubista E, Gnant M, Menzel C, Bauernhofer T, Seifert M, Haider K, Mlineritsch B, Steindorfer P, Kwasny W, Fridrik M, Steger G, Wette V, Samonigg H: Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate, and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormoneresponsive breast cancer-Austrian Breast and Colorectal Cancer Study Group Trial 5. J Clin Oncol 20: 4621-4627, 2002

    Google Scholar 

  9. The ATAC Trialists' Group: 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 359: 2131-2139, 2002

    Google Scholar 

  10. Carlson RW, Anderson BO, Bensinger W, Burstein H, Cox CE, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hudis C, Ljung B-M, Marks L, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silva E, Silver SM, Smith ML, Somlo G, Theirault R, Ward JH, Winer EP, Wolff A: NCCN Practice Guidelines for Breast Cancer. JNCCN 1: 148-188, 2003

    Google Scholar 

  11. Buzdar AU, Hortobagyi G: Update on endocrine therapy for breast cancer. Clin Cancer Res 4: 527-534, 1998

    Google Scholar 

  12. Hortobagyi GN: Progress in endocrine therapy for breast carcinoma. Cancer 83: 1-6, 1998

    Google Scholar 

  13. Early Breast Cancer Trialists' Collaborative Group: Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. An overview of 61 randomized trials among 28,896 women. N Engl J Med 319: 1681-1692, 1988

    Google Scholar 

  14. Klijn JG, Beex LV, Mauriac L, van Zijl JA, Veyret C, Wildiers J, Jassem J, Piccart M, Burghouts J, Becquart D, Seynaeve C, Mignolet F, Duchateau L: Combined treatment with buserelin and tamoxifen in premenopausal metastatic breast cancer: a randomized study. J Natl Cancer Inst. 92: 903-911, 2000

    Google Scholar 

  15. Klijn JG, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R, Combined Hormone Trialists' Group and the European Organization for Research and Treatment of Cancer: Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol 19: 343-353, 2001

    Google Scholar 

  16. Lundgren S, Gundersen S, Klepp R, Lonning PE, Lund E, Kvinnsland S: Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Res Treat 14: 201-206, 1989

    Google Scholar 

  17. Buzdar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL, Eiermann W, Wolter JM, Azab M, Webster A, Plourde PV: Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Arimidex Study Group. J Clin Oncol 14: 2000-2011, 1996

    Google Scholar 

  18. Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J, Bezwoda W, Gardin G, Gudgeon A, Morgan M, Fornasiero A, Hoffmann W, Michel J, Hatschek T, Tjabbes T, Chaudri HA, Hornberger U, Trunet PF: Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate. J Clin Oncol 16: 453-461, 1998

    Google Scholar 

  19. Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R, Porter L, Nabholtz J, Xiang X, Brady C: Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. J Clin Oncol 19: 3357-3366, 2001

    Google Scholar 

  20. Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N, Dugardyn JL, Nasurdi C, Mennel RG, Cervek J, Fowst C, Polli A, di Salle E, Arkhipov A, Piscitelli G, Miller LL, Massimini G: Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. The Exemestane Study Group. J Clin Oncol 18: 1399-1411, 2000

    Google Scholar 

  21. Bonneterre J, Buzdar A, Nabholtz JM, Robertson JF, Thürlimann B, von Euler M, Sahmoud T, Webster A, Steinberg M, Arimidex Writing Committee, Investigators Committee Members: Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 92: 2247-2258, 2001

    Google Scholar 

  22. Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M: Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19: 2596-2606, 2001

    Google Scholar 

  23. Buzdar A: The ATAC ('Arimidex', tamoxifen, alone or in combination) trial in postmenopausal women with early breast cancer-updated efficacy results based on a median follow-up of 47 months. Breast Cancer Res Treat 77: 295, 2003

    Google Scholar 

  24. Sainsbury R: Beneficial side-effect profile of anastrozole compared with tamoxifen confirmed by additional 7 months of exposure data: a safety update from the ‘Arimidex’, tamoxifen, alone or in combination (ATAC) trial. Breast Cancer Res Treat 76(Suppl. 1): S156, 2002 (abstract 633)

    Google Scholar 

  25. Thürlimann B, Robertson JFR, Bonneterre J: Efficacy of tamoxifen following Arimidex (anastrozole) as first-line treatment for advanced breast cancer (ABC) in postmenopausal women (PM). Breast Cancer Res Treat 64(Suppl.): S51, 2000

    Google Scholar 

  26. Thürlimann B, Hess D, Koeberle D, Senn I, Ballabeni P, Pagani O, Perey L, Aebi S, Rochlitz C, Goldhirsch A: Anastrozole ('Arimidex') versus tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer: results of the double-blind crossover SAKK trial 21/95-a sub-study of anastrozole trial 0027. Breast Cancer Res Treat 76(Suppl. 1): S73, 2002 (abstract 255)

    Google Scholar 

  27. Lønning PE, Bajetta E, Murray R, Tubiana-Hulin M, Eisenberg PD, Mickiewicz E, Celio L, Pitt P, Mita M, Aaronson NK, Fowst C, Arkhipov A, di Salle E, Polli A, Massimini G: Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol 18: 2234-2244, 2000

    Google Scholar 

  28. Robertson JF, Nicholson RI, Bundred NJ, Anderson E, Rayter Z, Dowsett M, Fox JN, Gee JM, Webster A, Wakeling AE, Morris C, Dixon M: Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer. Cancer Res 61: 6739-6746, 2001

    Google Scholar 

  29. Wakeling AE, Dukes M, Bowler J: A potent specific pure antiestrogen with clinical potential. Cancer Res 51: 3867-3873, 1991

    Google Scholar 

  30. Robertson JFR, Howell A, Abram P, Lichinitser M, Elledge R: Fulvestrant versus tamoxifen for the first-line treatment of advanced breast cancer (ABC) in postmenopausal women. Ann Oncol 13(Suppl. 5): 46, 2002 (abstract 1640)

    Google Scholar 

  31. Howell A, Robertson JFR, Quaresma Albano J, Aschermannova A, Mauriac L, Kleeberg UR, Vergote I, Erikstein B, Webster A, Morris C: Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol 20: 3396-3403, 2002

    Google Scholar 

  32. Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S, Gertler SZ, May JT, Burton G, Dimery I, Webster A, Morris C, Elledge R, Buzdar A: Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20: 3386-3395, 2002

    Google Scholar 

  33. Howell A: Postmenopausal women with advanced breast cancer who progress on fulvestrant or tamoxifen retain sensitivity to further endocrine therapies. Breast Cancer Res Treat 76(Suppl. 1): S72, 2002 (abstract 251)

    Google Scholar 

  34. Vergote I, Robertson JFR, Kleeberg U, Burton G, Osborne CK, Mauriac L: Postmenopausal women who progress on fulvestrant ('Faslodex') remain sensitive to further endocrine therapy. Breast Cancer Res Treat (in press)

  35. Perey L, Thürlimann B, Hawle H, Bonnefoi H, Ahern J, Pagani O, Goldhirsch A, Dietrich D: Fulvestrant ('faslodex') as hormonal treatment in postmenopausal patients with advanced breast cancer progressing after treatment with tamoxifen and aromatase inhibitors. Breast Cancer Res Treat 76(Suppl. 1): S72, 2002 (abstract 249)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Stanford University, Palo Alto, USA

    Robert W. Carlson

  2. University of California, San Francisco, CA, USA

    I. Craig Henderson

Authors
  1. Robert W. Carlson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Craig Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carlson, R.W., Craig Henderson, I. Sequential Hormonal Therapy for Metastatic Breast Cancer after Adjuvant Tamoxifen or Anastrozole. Breast Cancer Res Treat 80 (Suppl 1), 19–26 (2003). https://doi.org/10.1023/A:1025459232293

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025459232293

Search

Navigation