Adjuvant Ovarian Suppression Versus Chemotherapy for Premenopausal, Hormone-responsive Breast Cancer: Quality of Life and Efficacy Tradeoffs
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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.
Keywordsadjuvant therapy breast cancer chemotherapy decision analysis ovarian suppression quality of life
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- 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.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.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
- 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
- 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
- 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.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.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.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.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.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.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.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.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
- 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.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.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
- 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
- 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.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
- 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
- 40.Early Breast Cancer Trialists’ Collaborative Group: Ovarian ablation in early breast cancer: overview of the randomised trials. Lancet 348: 1189–1196, 1996Google Scholar
- 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.Burstein, HJ, Winer, EP 2000
Reproductive IssuesHarris, JR eds. Diseases of the BreastLippincottPhiladelphia10511059Google Scholar
- 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
- 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
- 56.Rostom AY: The management of menopausal sequelae in patients with breast cancer. Clinical Oncology 13, 2001Google Scholar
- 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