Breast Cancer Research and Treatment

, Volume 93, Issue 1, pp 25–34 | Cite as

Adjuvant Ovarian Suppression Versus Chemotherapy for Premenopausal, Hormone-responsive Breast Cancer: Quality of Life and Efficacy Tradeoffs

  • Elena B. Elkin
  • Milton C. Weinstein
  • Karen M. Kuntz
  • Craig A. Bunnell
  • Jane C. Weeks


Purpose. Recent clinical trials suggest that adjuvant ovarian suppression may be an equally effective and less toxic alternative to systemic chemotherapy in premenopausal women with hormone-responsive breast cancer. We used a decision-analytic framework to evaluate tradeoffs between efficacy and quality of life in the choice between these treatments.

Patients and methods. We used a Markov state-transition model to simulate clinical practice in a cohort of 40-year-old premenopausal women with newly diagnosed, hormone-responsive early breast cancer. We assessed three adjuvant treatments: chemotherapy, surgical ovarian suppression, and medical ovarian suppression. Outcomes were recurrence-free, overall, and quality-adjusted survival. Quality-adjusted survival reflected effects of cancer, treatment-related side effects, and menopausal symptoms.

Results. Assuming equal efficacy, ovarian suppression was superior to chemotherapy when the relative utility of chemotherapy side effects compared with ovarian suppression side effects was less than 0.95. Results were sensitive to assumptions about the likelihood, duration and consequences of treatment-induced menopause. Treatment choice was affected by a 7% proportional increase in the efficacy of one therapy relative to the others, independent of other factors.

Conclusion. If adjuvant chemotherapy and ovarian suppression have similar efficacy, then there may be a subgroup of women for whom quality-of-life considerations dominate the choice of treatment. However, small differences in the relative efficacy of these therapies have a substantial impact on treatment choice, regardless of side effects and menopausal transitions.


adjuvant therapy breast cancer chemotherapy decision analysis ovarian suppression quality of life 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Early Breast Cancer Trialists’ Collaborative Group: Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352: 930–942, 1998Google Scholar
  2. 2.
    Henderson, IC, Berry, DA, Demetri, GD, Cirrincione, CT, Goldstein, LJ, Martino, S, Ingle, JN, Cooper, MR, Hayes, DF, Tkaczuk, KH, Fleming, G, Holland, JF, Duggan, DB, Carpenter, JT, Frei, E, Schilsky, RL, Wood, WC, Muss, HB, Norton, L 2003Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancerJ Clin Oncol21976983CrossRefPubMedGoogle Scholar
  3. 3.
    Citron, ML, Berry, DA, Cirrincione, C, Hudis, C, Winer, EP, Gradishar, WJ, Davidson, NE, Martino, S, Livingston, R, Ingle, JN, Perez, EA, Carpenter, J, Hurd, D, Holland, JF, Smith, BL, Sartor, CI, Leung, H, Abrams, J, Schilsky, RL, Muss, HB, Norton, L 2003Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B trial 9741J Clin Oncol2114311439CrossRefPubMedGoogle Scholar
  4. 4.
    Partridge, AH, Burstein, HJ, Winer, EP 2001Side effects of chemotherapy and combined chemohormonal therapy in women with early-stage breast cancerJ Natl Cancer Inst Monogr30135142PubMedGoogle Scholar
  5. 5.
    Shapiro, C, Recht, A 2001Drug therapy: side effects of adjuvant treatment of breast cancerNew Engl J Med34419972008CrossRefPubMedGoogle Scholar
  6. 6.
    Valagussa, P, Zambetti, M, Biasi, S, Moliterni, A, Zucali, R, Bonadonna, G 1994Cardiac effects following adjuvant chemotherapy and breast irradiation in operable breast cancerAnn Oncol5209216PubMedGoogle Scholar
  7. 7.
    Zambetti, M, Moliterni, A, Stefanelli, M, Cipriani, S, Valagussa, P, Bonadonna, G, Gianni, L 2001Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiationJ Clin Oncol193743PubMedGoogle Scholar
  8. 8.
    Curtis, RE, Boice, JD, Stovall, M, Bernstein, L, Greenberg, RS, Flannery, JT, Schwartz, AG, Weyer, P, Moloney, WC, Hoover, RN 1992Risk of leukemia after chemotherapy and radiation treatment for braest cancerNew Engl J Med32617451751PubMedGoogle Scholar
  9. 9.
    Tallman, MS, Gray, R, Bennett, JM, Variakojis, D, Robert, N, Wood, WC, Rowe, JM, Wiernik, PH 1995Leukemogenic potential of adjuvant chemotherapy for early-stage breast cancer: the Eastern Cooperative Oncology Group experienceJ Clin Oncol1315571563PubMedGoogle Scholar
  10. 10.
    Diamandidou, E, Buzdar, AU, Smith, TL, Frye, D, Witjaksono, M, Hortobagyi, GN 1996Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experienceJ Clin Oncol1427222730PubMedGoogle Scholar
  11. 11.
    Del Mastro, L, Venturini, M, Sertoli, MR, Rosso, R 1997Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implicationsBreast Cancer Res Treat43183190CrossRefPubMedGoogle Scholar
  12. 12.
    Pagani, O, O’Neill, A, Castiglione, M, Gelber, RD, Goldhirsch, A, Rudenstam, CM, Lindtner, J, Collins, J, Crivellari, D, Coates, A, Cavalli, F, Thurlimann, B, Simoncini, E, Fey, M, Price, K, Senn, HJ 1998Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the Internation Breast Cancer Study Group (IBCSG) Trial VIEur J Cancer34632640CrossRefPubMedGoogle Scholar
  13. 13.
    Poikonen, P, Saarto, T, Elomaa, I, Joensuu, H, Blomqvist, C 2000Prognostic effect of amenorrhea and elevated serum gonadotropin levels induced by adjuvant chemotherapy in premenopausal node-positive breast cancer patientsEur J Cancer364348CrossRefPubMedGoogle Scholar
  14. 14.
    Ejlertsen B, Dombernowsky P, Mouridsen HT, Kamby C, Kjaer M, Rose C, Andersen KW, Jensen MB, Bengtsson NO, Bergh J: Comparable effect of ovarian ablation and CMF chemotherapy in premenopausal hormone receptor positive patients. Proc Am Soc Clin Oncol 18: 66a (abstract 248), 1999Google Scholar
  15. 15.
    Scottish Cancer Trials Breast Group: Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma. Lancet 341: 1293–1298, 1993Google Scholar
  16. 16.
    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 2000Cyclophosphamide, 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 TrialJ Clin Oncol1827182727PubMedGoogle Scholar
  17. 17.
    Roche HH, Kerbrat P, Bonneterre J, Fargeot P, Fumoleau P, Monnier A, Chappelle-Marcillac I, Bardonnet M: Complete hormonal blockade versus chemotherapy in premenopausal early-stage breast cancer patients with positive hormone receptor and 1–3 node-positive tumor: results of the FASG 06 trial. Proc Am Soc Clin Oncol 19: 72a (abstract 279), 2000Google Scholar
  18. 18.
    Wallwiener D, Possinger K, Bondar G, Huober J, Schmid P, Kienle E, Untch M: Leuprorelin acetate vs. CMF in the adjuvant treatment of premenopausal women with ER/PR-positive, node-positive breast cancer: interim results of the TABLE study. Proc Am Soc Clin Oncol 20 (abstr 132), 2001Google Scholar
  19. 19.
    International Breast Cancer Study Group: Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: A randomized trial. J Natl Cancer Inst 95: 1833–1846, 2003Google Scholar
  20. 20.
    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 2002Randomized 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 – the Austrain Breast and Colorectal Study Group trial 5J Clin Oncol2046214627CrossRefPubMedGoogle Scholar
  21. 21.
    Jonat, W, Kaufmann, M, Sauerbrei, W, Blamey, R, Cuzick, J, Namer, M, Fogelman, I, Haes , H, Matteis, A, Stewart, A, Eiermann, W, Szakolczai, I, Palmer, M, Schumacher, M, Geberth, M, Lisboa, B 2002Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: the Zoladex Early Breast Cancer Research Association studyJ Clin Oncol2046284635CrossRefPubMedGoogle Scholar
  22. 22.
    Haes, H, Olschewski, M, Kaufmann, M, Schumacher, M, Jonat, W, Sauerbrei, W 2003Quality of life in goserelin-treated versus cyclophosphamide + methotrexate + fluorouracil-treated premenopausal and perimenopausal patients with node-positive, early breast cancer: The Zoladex Early Breast Cancer Research Association Trialists GroupJ Clin Oncol2145104516CrossRefPubMedGoogle Scholar
  23. 23.
    Fallowfield, L, McGurk, R, Dixon, M 2004Same gain, less pain: potential patient preferences for adjuvant treatment in premenopausal women with early breast cancerEur J Cancer4024032410CrossRefPubMedGoogle Scholar
  24. 24.
    Sonnenberg, FA, Beck, JR 1993Markov models in medical decision-making: a practical guideMed Decis Making13322338PubMedGoogle Scholar
  25. 25.
    Lee, JH, Glick, HA, Hayman, JA, Solin, LJ 2002Decision-analytic model and cost-effectiveness evaluation of postmastectomy radiation therapy in high-risk premenopausal breast cancer patientsJ Clin Oncol2027132725CrossRefPubMedGoogle Scholar
  26. 26.
    Schrag, D, Kuntz, KM, Garber, JE, Weeks, JC 1997Decision analysis: effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutationsNew Engl J Med33614651471CrossRefPubMedGoogle Scholar
  27. 27.
    Tormey, DC, Gray, R, Gilchrist, K, Grace, T, Carbone, PP, Wolter, J, Woll, JE, Cummings, FJ 1990Adjuvant chemohormonal therapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP) or CMFP plus tamoxifen compared with CMF for premenopausal breast cancer patients: and Eastern Cooperative Oncology Group trialCancer65200206PubMedGoogle Scholar
  28. 28.
    Recht, A, Gray, R, Davidson, NE, Fowble, BL, Solin, LJ, Cummings, FJ, Falkson, G, Falkson, HC, Taylor, SG, Tormey, DC 1999Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology GroupJ Clin Oncol1716891700PubMedGoogle Scholar
  29. 29.
    Jakesz, R, Hausmaninger, H, Haider, K, Kubista, E, Samonigg, H, Gnant, M, Manfreda, D, Tschurtschenthaler, G, Kolb, R, Stierer, M, Fridrik, M, Mlineritsch, B, Steindorfer, P, Mittlbock, M, Steger, G 1999Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancerJ Clin Oncol1717011709PubMedGoogle Scholar
  30. 30.
    Aberizk, WJ, Silver, B, Henderson, IC, Cady, B, Harris, JR 1986The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomyCancer5812141218PubMedGoogle Scholar
  31. 31.
    Fourquet, A, Campana, F, Zafrani, B, Mosseri, V, Vielh, P, Durand, JC, Vilcoq, JR 1989Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-upInt J Radiation Oncol Biol Phys17719725Google Scholar
  32. 32.
    Kurtz, JM, Amalric, R, Brandone, H, Ayme, Y, Jacquemier, J, Pietra, JC, Hans, D, Pollet, JF, Bressac, C, Spitalier, JM 1989Local recurrence after breast-conserving surgery and radiotherapy. Frequency, time course, and prognosisCancer6319121917PubMedGoogle Scholar
  33. 33.
    Schwaibold F, Fowble BL, Solin LJ, Schultz DJ, Goodman RL: The results of radiation therapy for local recional recurrence after mastectomy. Int J Radiation Oncol Biol Phys 21, 1991Google Scholar
  34. 34.
    Halverson, KJ, Perez, CA, Kuske, RP, Garcia, DM, Simpson, JR, Fineberg, B 1992Survival following locoregional recurrence of breast cancer: univariate and multivariate analysisInt J Radiation Oncol Biol Phys23285291Google Scholar
  35. 35.
    Veronesi, U, Marubini, E, Del Vecchio, M, Manzari, A, Andreola, S, Greco, M, Luini, A, Merson, M, Saccozzi, R, Rilke, F 1995Local recurrences and distant metastases after conservative breast cancer treatments: partly independent eventsJ Natl Cancer Inst871927PubMedGoogle Scholar
  36. 36.
    Fortin, A, Larochelle, M, Laverdiere, J, Lavertu, S, Tremblay, D 1999Local failure is responsible for the decrease in survival for patients with breast cancerJ Clin Oncol17101109PubMedGoogle Scholar
  37. 37.
    Schmoor, C, Saurbrei, W, Schumacher, M 2000Role of isolated locoregional recurrence of breast cancer: results of four prospective studiesJ Clin Oncol1816961708PubMedGoogle Scholar
  38. 38.
    Surveillance, Epidemiology, and End Results (SEER) Program: Public-Use Data (1973–1999), November 2001 submission. National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch; 2002.Google Scholar
  39. 39.
    Punglia, RS, Kuntz, KM, Lee, JH, Recht, A 2003Radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery in postmenopausal women with stage I breast cancer: a decision analysisJ Clin Oncol2122602267CrossRefPubMedGoogle Scholar
  40. 40.
    Early Breast Cancer Trialists’ Collaborative Group: Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet 348: 1189–1196, 1996Google Scholar
  41. 41.
    Colditz, GA, Willett, WC, Stampfer, MJ, Rosner, B, Speizer, FE, Hennekens, CH 1987Menopause and the risk of coronary heart disease in womenNew Engl J Med31611051110PubMedGoogle Scholar
  42. 42.
    Schow, YT, Graaf, Y, Steyerberg, EW, Eijkemans, MJC, Banga, JD 1996Age at menopause as a risk factor for cardiovascular mortalityLancet347714718CrossRefPubMedGoogle Scholar
  43. 43.
    Jacobsen, BK, Knutsen, SF, Fraser, GE 1999Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health StudyJ Clin Epi52303307CrossRefGoogle Scholar
  44. 44.
    Hunink, M, Glasziou, P, Siegel, J, Weeks, J, Pliskin, J, Elstein, A, Weinstein, M 2001Decision-Making in Health and Medicine: Integrating Evidence and ValuesCambridge University PressNew YorkGoogle Scholar
  45. 45.
    Burstein, HJ, Winer, EP 2000

    Reproductive Issues

    Harris, JR eds. Diseases of the BreastLippincottPhiladelphia10511059
    Google Scholar
  46. 46.
    van Der Voort, DJ, Weijer, PH, Barentsen, R 2003Early menopause: increased fracture risk at older ageOsteoporos Int14525530CrossRefPubMedGoogle Scholar
  47. 47.
    Headley, JA, Theriault, RL, LeBlanc, AD, Vassilopoulou-Sellin, R, Hortobagyi, GN 1998Pilot study of bone mineral density in breast cancer patient treated with adjuvant chemotherapyCancer Invest16611PubMedGoogle Scholar
  48. 48.
    Pouilles, JM, Tremollieres, F, Bonneu, M, Ribot, C 1994Influence of early age at menopause on vertebral bone massJ Bone Miner Res9311315PubMedGoogle Scholar
  49. 49.
    Partridge AH, Gelber RD, Knudsen K, Laufer M, Rosenberg R, Michele P, Rein A, Winer EP: A web-based survey of fertility issues in young women with breast cancer. Breast Cancer Res Treat 82: S15 (abstract 31), 2003Google Scholar
  50. 50.
    Cooper, GS, Sandler, DP 1998Age at natural menopause and mortalityAnn Epidemiol8229235CrossRefPubMedGoogle Scholar
  51. 51.
    Earle, CC, Chapman, RH, Baker, CS, Bell, CM, Stone, PW, Sandberg, EA, Neumann, PJ 2000Systematic overview of cost-utility assessments in oncologyJ Clin Oncol1833023317PubMedGoogle Scholar
  52. 52.
    Goodwin, PJ, Ennis, M, Pritchard, KI, Trudeau, M, Hood, N 1999Risk of menopause during the first year after breast cancer diagnosisJ␣Clin Oncol1723652370PubMedGoogle Scholar
  53. 53.
    Lin, EM, Aikin, JL, Good, BC 1999Premature menopause after cancer treatmentCancer Practice7114121CrossRefPubMedGoogle Scholar
  54. 54.
    Treatment of estrogen deficiency symptoms in women surviving breast cancer. Part 4: Urogenital atrophy, vasomotor instability, sleep disorders, and related symptoms. Oncology 13: 551–575, 1999Google Scholar
  55. 55.
    Ganz, PA 2001Menopause and breast cancer: symptoms, late effects, and their managementSemin Oncol28274283CrossRefPubMedGoogle Scholar
  56. 56.
    Rostom AY: The management of menopausal sequelae in patients with breast cancer. Clinical Oncology 13, 2001Google Scholar
  57. 57.
    DiLeo, A, Buyse, M 2002Equivalence between ovarian suppression and chemotherapy in the adjuvant treatment of endocrine-responsive breast cancer (letter)J Clin Oncol2019541955PubMedGoogle Scholar
  58. 58.
    Roberts NJ, Wang M, Cella DF, Martino S, Tripathy D, Ingle J, Solin LJ, Wood WC: Phase III comparison of tamoxifen versus tamoxifen with ovarian ablation in premenopausal women with axillary node-negative receptor positive breast cancer < 3 cm. Proc Am Soc Clin Oncol 22: 5 (abstract 16), 2003Google Scholar
  59. 59.
    Featherstone, CJ, Harnett, AN, Brunt, AM, Johnson, L 2002Methods of ovarian suppression used in the UKBreast112329CrossRefPubMedGoogle Scholar
  60. 60.
    Dees, EC, Davidson, NE 2001Ovarian ablation as adjuvant therapy for breast cancerSemin Oncol28322331CrossRefPubMedGoogle Scholar
  61. 61.
    Goldhirsch, A, Glick, JH, Gelber, RD, Coates, AS, Senn, HJ 2001Meeting highlights: International consensus panel on the treatment of primary breast cancerJ Clin Oncol1938171827PubMedGoogle Scholar
  62. 62.
    Love, RR 2002Meeting highlights: international consensus panel on the treatment of primary breast cancer (letter)J Clin Oncol2019551956CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Elena B. Elkin
    • 1
  • Milton C. Weinstein
    • 2
  • Karen M. Kuntz
    • 2
  • Craig A. Bunnell
    • 3
  • Jane C. Weeks
    • 3
  1. 1.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Health Policy and ManagementHarvard School of Public HealthBoston
  3. 3.Department of Adult OncologyDana-Farber Cancer InstituteBoston

Personalised recommendations