Drugs

, Volume 67, Issue 10, pp 1393–1401 | Cite as

Treatment of Premenopausal Women with Early Breast Cancer

Old Challenges and New Opportunities
Current Opinion

Abstract

Breast cancer occurring in women before the age of menopause continues to be a major medical and psychological challenge. Endocrine therapy has emerged as the mainstay of adjuvant treatment for women with estrogen receptor-positive tumours. Although the suppression of ovarian function (by oophorectomy, irradiation of the ovaries or gonadotropin releasing factor analogues) is effective as adjuvant therapy if used alone, its value has not been proven after chemotherapy. This is presumably because of the frequent occurrence of chemotherapy-induced amenorrhoea. Tamoxifen reduces the risk of recurrence by approximately 40%, irrespective of age and the ovarian production of estrogens. The worth of ovarian function suppression in combination with tamoxifen is unproven and is being investigated in an intergroup randomised clinical trial (SOFT [Suppression of Ovarian Function Trial]). Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are only being investigated in younger patients. The use of chemotherapies is identical in younger and older patients; however, at present the efficacy of chemotherapy in addition to ovarian function suppression plus tamoxifen is unknown in premenopausal patients with endocrine responsive disease. ‘Targeted’ therapies such as monoclonal antibodies to human epidermal growth factor receptor (HER)-2, HER1 and vascular endothelial growth factor, ‘small molecule’ inhibitors of tyrosine kinases and breast cancer vaccines are rapidly emerging. Their use depends on the function of the targeted pathways and is presently limited to clinical trials. Premenopausal patients are best treated in the framework of a clinical trial.

References

  1. 1.
    Ries LAG, Harkins D, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2003, National Cancer Institute, Bethesda, MD, based on November 2005 SEER data submission, posted to the SEER web site, 2006 [online]. Available from URL: http://seer.cancer.gov/csr/1975_2003/ [Accessed 2006 Aug 6]
  2. 2.
    Adami HO, Malker B, Holmberg L, et al. The relation between survival and age at diagnosis in breast cancer. N Engl J Med 1986; 315: 559–63PubMedCrossRefGoogle Scholar
  3. 3.
    de la Rochefordiere A, Asselain B, Campana F, et al. Age as prognostic factor in premenopausal breast carcinoma. Lancet 1993; 341: 1039–43PubMedCrossRefGoogle Scholar
  4. 4.
    Nixon AJ, Neuberg D, Hayes DF, et al. Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 1994; 12: 888–94PubMedGoogle Scholar
  5. 5.
    Dubsky PC, Gnant MF, Taucher S, et al. Young age as an independent adverse prognostic factor in premenopausal patients with breast cancer. Clin Breast Cancer 2002; 3: 65–72PubMedCrossRefGoogle Scholar
  6. 6.
    Colleoni M, Rotmensz N, Robertson C, et al. Very young women (<35 years) with operable breast cancer: features of disease at presentation. Ann Oncol 2002; 13: 273–9PubMedCrossRefGoogle Scholar
  7. 7.
    Albain KS, Allred DC, Clark GM. Breast cancer outcome and predictors of outcome: are there age differentials? J Natl Cancer Inst Monogr 1994; 16: 35–42PubMedGoogle Scholar
  8. 8.
    Braun S, Vogl FD, Naume B, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353: 793–802PubMedCrossRefGoogle Scholar
  9. 9.
    Aebi S, De Ridder G, Vlastos G, et al. Young age is a poor prognostic factor in women with stage I breast cancer. Eur J Cancer 2006; (2 Suppl. 4): 121Google Scholar
  10. 10.
    Kroman N, Jensen M-B, Wohlfahrt J, et al. Factors influencing the effect of age on prognosis in breast cancer: population based study. Commentary: much still to learn about relations between tumour biology, prognosis, and treatment outcome in early breast cancer. BMJ 2000; 320: 474–9PubMedCrossRefGoogle Scholar
  11. 11.
    Goldhirsch A, Glick JH, Gelber RD, et al. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 2005; 16: 1569–83PubMedCrossRefGoogle Scholar
  12. 12.
    Early Breast Cancer Trialists’ Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687–717CrossRefGoogle Scholar
  13. 13.
    Arriagada R, Le MG, Spielmann M, et al. Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy. Ann Oncol 2005; 16: 389–96PubMedCrossRefGoogle Scholar
  14. 14.
    Goodwin PJ, Ennis M, Pritchard KI, et al. Risk of menopause during the first year after breast cancer diagnosis. J Clin Oncol 1999; 17: 2365–70PubMedGoogle Scholar
  15. 15.
    Petrek JA, Naughton MJ, Case LD, et al. Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 2006; 24: 1045–51PubMedCrossRefGoogle Scholar
  16. 16.
    Castiglione-Gertsch M, O’Neill A, Price KN, et al. Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: a randomized trial. J Natl Cancer Inst 2003; 95: 1833–46PubMedCrossRefGoogle Scholar
  17. 17.
    Davidson NE, O’Neill AM, Vukov AM, et al. Chemoendocrine therapy for premenopausal women with axillary lymph nodepositive, steroid hormone receptor-positive breast cancer: results from INT 0101 5188. J Clin Oncol 2005; 23: 5973–82PubMedCrossRefGoogle Scholar
  18. 18.
    Scottish Cancer Trials Breast Group and ICRF Breast Unit. Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: the Scottish trial. Lancet 1993; 341: 1293–8Google Scholar
  19. 19.
    Ejlertsen B, Mouridsen HT, Jensen MB, et al. Similar efficacy for ovarian ablation compared with cyclophosphamide, methotrexate, and fluororacil: from a randomized comparison of premenopausal patients with node-positive, hormon receptor-positive breast cancer. J Clin Oncol 2006; 24: 4956–62PubMedCrossRefGoogle Scholar
  20. 20.
    Jonat W, Kaufmann M, Sauerbrei W, et al. Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: the Zoladex Early Breast Cancer Research Association study. J Clin Oncol 2002; 20: 4628–35PubMedCrossRefGoogle Scholar
  21. 21.
    Wallwiener D, Possinger K, Schmid P, et al. A phase III trial comparing adjuvant treatment with leuprorelin acetate 3M-Depot for 24 months with CMF chemotherapy in ER/PR + node + pre-perimenopausal breast cancer patients. J Clin Oncol 2004; 22: 533Google Scholar
  22. 22.
    von Minckwitz G, Graf E, Geberth M, et al. CMF versus goserelin as adjuvant therapy for node-negative, hormone-receptor-positive breast cancer in premenopausal patients: a randomised trial (GABG trial IV-A-93). Eur J Cancer 2006; 42: 1780–8CrossRefGoogle Scholar
  23. 23.
    Roché H, Mihura J, de Lafontan B, et al. Castration and tamoxifen vs chemotherapy (FAC) for premenopausal, node and receptors positive breast cancer patients: a randomized trial with a 7 years follow-up [abstract]. Proc Am Soc Clin Oncol 1996; 15: 117Google Scholar
  24. 24.
    Boccardo F, Rubagotti A, Amoroso D, et al. Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. J Clin Oncol 2000; 18: 2718–27PubMedGoogle Scholar
  25. 25.
    Jakesz R, Hausmaninger H, Kubista E, et al. 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 hormone-responsive breast cancer. Austrian Breast and Colorectal Cancer Study Group trial 5. J Clin Oncol 2002; 20: 4621–7Google Scholar
  26. 26.
    Roché H, Kerbrat P, Bonneterre J, et al. Complete hormonal blockade versus epirubicin-based chemotherapy in premenopausal, one to three node-positive, and hormone-receptor positive, early breast cancer patients: 7-year follow-up results of French Adjuvant Study Group 06 randomised trial. Ann Oncol 2006; 17: 1221–7PubMedCrossRefGoogle Scholar
  27. 27.
    Early Breast Cancer Trialists’ Collaborative Group. Web annexes: effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005 May [cited 365 9472]; 1687–1717 [online]. Available from URL: http://www.ctsu.ox.ac.uk/~ebctcg/ [Accessed 2006 Aug 20]
  28. 28.
    International Breast Cancer Study Group. Tamoxifen after adjuvant chemotherapy for premenopausal women with lymph node-positive breast cancer: International Breast Cancer Study Group Trial 13–93. J Clin Oncol 2006; 24: 1332–41CrossRefGoogle Scholar
  29. 29.
    Klijn JG, Blarney RW, Boccardo F, et al. 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 2001; 19: 343–53PubMedGoogle Scholar
  30. 30.
    Baum M, Hackshaw A, Houghton J, et al. Adjuvant goserelin in pre-menopausal patients with early breast cancer: results from the ZIPP study. Eur J Cancer 2006; 42: 895–904PubMedCrossRefGoogle Scholar
  31. 31.
    Robert NJ, Wang M, Cella D, et al. Phase III comparison of tamoxifen versus tamoxifen with ovarian ablation in premenopausal women with axillary node-negative receptor-positive breast cancer < = 3 cm [abstract no. 16]. Proc Am Soc Clin Oncol 2003; 22: 5Google Scholar
  32. 32.
    IBCSG 24-02. Suppression of ovarian function plus either tamoxifen or exemestane compared with tamoxifen alone in treating premenopausal women with hormone-responsive breast cancer, 2002 [online]. Available from URL: http://www.cancer.gov/search/ViewClinicalTrials.aspx7.cdrid=316456&version=patient&protocolsearchid=1389656 [Accessed 2005 Jan 19]
  33. 33.
    Love RR, Duc NB, Allred DC, et al. Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer. J Clin Oncol 2002; 20: 2559–66PubMedCrossRefGoogle Scholar
  34. 34.
    Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005; 365: 60–2PubMedCrossRefGoogle Scholar
  35. 35.
    Thurlimann B, Keshaviah A, Coates AS, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med 2005; 353: 2747–57PubMedCrossRefGoogle Scholar
  36. 36.
    Smith IE, Dowsett M, Yap YS, et al. Adjuvant aromatase inhibitors for early breast cancer after chemotherapy-induced amenorrhoea: caution and suggested guidelines. J Clin Oncol 2006; 24: 2444–7PubMedCrossRefGoogle Scholar
  37. 37.
    Austrian Breast and Colorectal Cancer Study Group. Tamoxifen versus anastrozole, alone or in combination with zoledronic acid, 1999 [online]. Available from URL: http://www.clinicaltrial.gov/ct/show/NCT00295646?.order=4 [Accessed 2006 Aug 7]
  38. 38.
    Gnant MF, Mlineritsch B, Luschin-Ebengreuth G, et al. Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receivnig adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 2007; 25: 820–8PubMedCrossRefGoogle Scholar
  39. 39.
    IBCSG 25-02. Triptorelin with either exemestane or tamoxifen in treating premenopausal women with hormone-responsive breast cancer, 2002 [online]. Available from URL: http://www.cancer.gov/search/ViewClinicalTrials.aspx?.cdrid=316458&version=patient&protocolsearchid=1389656 [Accessed 2005 Jan 19]
  40. 40.
    Dana-Farber Cancer Institute. Fulvestrant in premenopausal women with hormone receptor-positive breast cancer, 2005 [online]. Available from URL: http://www.clinicaltrials.gov/ct/show/NCT00146601 [Accessed 2006 Aug 20]
  41. 41.
    Aebi S. Special issues related to the adjuvant therapy in very young women. Breast 2005; 14: 594–9PubMedCrossRefGoogle Scholar
  42. 42.
    Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. Jama 2006; 295: 1658–67PubMedCrossRefGoogle Scholar
  43. 43.
    Colleoni M, Bonetti M, Coates AS, et al. Early start of adjuvant chemotherapy may improve treatment outcome for premenopausal breast cancer patients with tumors not expressing estrogen receptors. The International Breast Cancer Study Group. J Clin Oncol 2000; 18: 584–90Google Scholar
  44. 44.
    International Breast Cancer Study Group. Randomized controlled trial of ovarian function suppression plus tamoxifen versus the same endocrine therapy plus chemotherapy: is chemotherapy necessary for premenopausal women with node-positive, endocrine responsive breast cancer? First results of International Breast Cancer Study Group Trial 11–93. Breast 2001; 10 Suppl. 3: 130–8Google Scholar
  45. 45.
    IBCSG 26-02. Suppression of ovarian function and either tamoxifen or exemestane with or without chemotherapy in treating premenopausal women with resected breast cancer, 2002 [online]. Available from URL: http://www.cancer.gov/search/ViewClinicalTrials.aspx?.cdrid=318832&version=patient&protocolsearchid=1396099 [Accessed 2005 Jan 19]
  46. 46.
    Brenton JD, Carey LA, Ahmed AA, et al. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol 2005; 23: 7350–60PubMedCrossRefGoogle Scholar
  47. 47.
    Woloshin S, Schwartz LM. What’s the rush? The dissemination and adoption of preliminary research results. J Natl Cancer Inst 2006; 98: 372–3PubMedCrossRefGoogle Scholar
  48. 48.
    Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER 2. N Engl J Med 2001; 344: 783–92PubMedCrossRefGoogle Scholar
  49. 49.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P, et al. Trastuzumab in combination with docetaxel or vinorelbine as adjuvant treatment of breast cancer: the FinHer trial [abstract no. 2]. Breast Cancer Res Treat 2005; 89 Suppl. 1: S2Google Scholar
  50. 50.
    Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353: 1673–84PubMedCrossRefGoogle Scholar
  51. 51.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353: 1659–72PubMedCrossRefGoogle Scholar
  52. 52.
    Smith I, Procter M, Gelber RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007; 369: 29–36PubMedCrossRefGoogle Scholar
  53. 53.
    Slamon D, Eiermann W, Robert N, et al. BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC-T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2neu positive early breast cancer patients [abstract no. 52]. San Antonio Breast Cancer Symposium; 2006 Dec 14–17; San Antonio (TX)Google Scholar
  54. 54.
    Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat 2005; 94 Suppl. 1: 3Google Scholar
  55. 55.
    Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23: 792–9PubMedCrossRefGoogle Scholar
  56. 56.
    Schneider BP, Sledge GW Jr. Drug insight: VEGF as a therapeutic target for breast cancer. Nat Clin Pract Oncol 2007; 4: 181–9PubMedCrossRefGoogle Scholar
  57. 57.
    Agus DB, Gordon MS, Taylor C, et al. Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol 2005; 23: 2534–43PubMedCrossRefGoogle Scholar
  58. 58.
    Cortes J, Baselga J, Kellokumpu-Lehtinen P, et al. Open label, randomized, phase II study of pertuzumab (P) in patients (pts) with metastatic breast cancer (MBC) with low expression of HER 2. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings (Part I); 23 (1 June Suppl.): 3068Google Scholar
  59. 59.
    Spector NL, Blackwell K, Hurley J, et al. EGF103009, a phase II trial of lapatinib monotherapy in patients with relapsed/ refractory inflammatory breast cancer (IBC): clinical activity and biologic predictors of response. J Clin Oncol, 2006 ASCO Annual Meeting Proceedings (Part I); 24 (20 June Suppl.): 502Google Scholar
  60. 60.
    Geyer CE, Forster JK, Lindquist D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355: 2733–43PubMedCrossRefGoogle Scholar
  61. 61.
    Chan S, Scheulen ME, Johnston S, et al. Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 2005; 23: 5314–22PubMedCrossRefGoogle Scholar
  62. 62.
    Carpenter JT, Roché H, Campone M, et al. Randomized 3-arm, phase 2 study of temsirolimus (CCI-779) in combination with letrozole in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings 2005; 23 (1 June Suppl.): 564Google Scholar
  63. 63.
    Milano A, Dal Lago L, Sotiriou C, et al. What clinicians need to know about antioestrogen resistance in breast cancer therapy. Eur J Cancer 2006; 42: 2692–705PubMedCrossRefGoogle Scholar
  64. 64.
    Peoples GE, Khoo S, Dehqanzada ZA, et al. Combined clinical trial results of a HER2/neu (E75) vaccine for prevention of recurrence in high-risk breast cancer patients [abstract no. 4]. Breast Cancer Res Treat 2006; 100 Suppl. 1: S6Google Scholar
  65. 65.
    Curigliano G, Spitaleri G, Pietri E, et al. Breast cancer vaccines: a clinical reality or fairy tale? Ann Oncol 2006; 17: 750–62PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Department of Medical OncologyUniversity Hospital, Berne, InselspitalBerneSwitzerland
  2. 2.Institute of Oncology of Southern SwitzerlandMendrisioSwitzerland

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