Advertisement

Osteoporosis International

, Volume 14, Issue 12, pp 1001–1006 | Cite as

Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF)

  • I. Fogelman
  • G. M. Blake
  • R. Blamey
  • M. Palmer
  • W. Sauerbrei
  • M. Schumacher
  • D. Serin
  • A. Stewart
  • W. Wilpshaar
Original Article

Abstract

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients (n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (six×28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2–L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were −10.5% and −6.5% (P=0.0005) for lumbar spine and −6.4% and −4.5% (P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.

Keywords

Bone mineral density Goserelin Node-positive early breast cancer Premenopausal ZEBRA 

Notes

Acknowledgements

The ZEBRA study is supported by a grant from AstraZeneca, Macclesfield, UK. Participating investigators: M. Geberth, Heidelberg, Germany; B. Lisboa, Hamburg, Germany; A.X. Izquierdo, Gerona, Spain; P. Firat, Ankara, Turkey; S.J. Leinster, Liverpool, UK.

References

  1. 1.
    Del Mastro L, Venturini M, Sertoli MR, Rosso R (1997) Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implications. Breast Cancer Res Treat 43:183–190CrossRefPubMedGoogle Scholar
  2. 2.
    Pagani O, O’Neill A, Castiglione M, Gelber RD, Goldhirsh A, Rudenstam CM et al. (1998) Prognostic impact of amenorrhea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI. Eur J Cancer 34:632–640CrossRefPubMedGoogle Scholar
  3. 3.
    Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M et al. (2002) 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 20:4628–4635CrossRefPubMedGoogle Scholar
  4. 4.
    Boccardo F, Rubagotti A, Amoroso D, Mesiti M, Romeo D, Sismondi P et al. (2000) 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 18:2718–2727PubMedGoogle Scholar
  5. 5.
    Jakesz R, Hausmaninger H, Samonigg H et al. (2001) Complete endocrine blockade with tamoxifen and goserelin is superior to CMF in the adjuvant treatment of premenopausal, lymph node-positive and -negative patients with hormone-responsive breast cancer. Breast 10:S10 (abstract S26)Google Scholar
  6. 6.
    Davidson N, O’Neill A, Vukov A, Osborne S, Martino D, White M.D (1999) Effect of chemohormonal therapy in premenopausal, node (+), receptor (+) breast cancer: an Eastern Cooperative Oncology Group Phase III Intergroup trial. Proc ASCO 18:67a (abstract 249)Google Scholar
  7. 7.
    Baum M, Houghton J, Odling-Smee W et al. (2001) Adjuvant Zoladex in premenopausal patients with early breast cancer: results from the ZIPP trial. Breast 10:S32–S33 (abstract P64)Google Scholar
  8. 8.
    de Haes H and the ZEBRA Trialists Group (2000) Comparison of quality of life in pre/perimenopausal women treated with Zoladex or CMF as adjuvant therapy for the management of node-positive early breast cancer: results from the ZEBRA study. Breast Pharmacokinet 39:27–48Google Scholar
  9. 9.
    Olschewski M, de Haes H (2001) The ZEBRA study: early benefits in quality of life in goserelin-treated vs CMF-treated pre/perimenopausal patients with node-positive early breast cancer. Eur J Cancer 37:S40 (abstract Q115)CrossRefGoogle Scholar
  10. 10.
    Jakesz R, Hausmaninger H, Kubista E, Gnant M, Menzel C, Bauernhofer T et al. (2002) Randomized adjuvant trial of tamoxifen plus goserelin versus cyclophosphamide, methotrexate and fluorouracil: evidence for the superiority of treatment with endocrine blockade in premenopausal patients with hormone-responsive breast cancer. J Clin Oncol 20:4621–4627CrossRefPubMedGoogle Scholar
  11. 11.
    Boccardo F, Rubagotti A, Amoroso D, Mesiti M, Romeo D, Aldrighetti D et al. (2001) CMF vs tamoxifen (TAM) plus ovarian suppression (OS) as adjuvant treatment of ER-positive (ER+) pre/perimenopausal breast cancer (BCA) patients. Breast 10:S32 (abstract P62)Google Scholar
  12. 12.
    Trevisan C, Ortolani S, Bianchi ML, Caraceni MP, Ulivieri FM, Gandolini G, Polli EE (1991) Age, time since menopause, and body parameters as determinants of female spinal bone mass: a mathematical model. Calcif Tiss Int 49:1–5Google Scholar
  13. 13.
    Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK et al. (1993) Bone density at various sites for prediction of hip fractures. The Study of Osteoporotic Fractures Research Group. Lancet 341:72–75PubMedGoogle Scholar
  14. 14.
    Tannirandorn P, Epstein S (2000) Drug-induced bone loss. Osteoporos Int 11:637–659CrossRefPubMedGoogle Scholar
  15. 15.
    Fogelman I (1996) The effects of estrogen deficiency on the skeleton and its prevention. Br J Obstet Gynaecol 103 (suppl 14):5–9PubMedGoogle Scholar
  16. 16.
    Saarto T, Blomqvist C, Valimaki M, Makela P, Sarna S, Elomaa I (1997) Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study in premenopausal breast cancer patients. J Clin Oncol 15:1341–1347PubMedGoogle Scholar
  17. 17.
    Melton LJ, Thamer M, Ray NF, Chan JK, Chesnut CH, Einhorn TA et al. (1997) Fractures attributable to osteoporosis: report from the National Osteoporosis Foundation. J Bone Miner Res 12:16–23PubMedGoogle Scholar
  18. 18.
    Peterson JA (2001) Osteoporosis overview. Geriatr Nurs 22:17–21CrossRefPubMedGoogle Scholar
  19. 19.
    Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C et al. (1976) Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med 294:405–410PubMedGoogle Scholar
  20. 20.
    Steiger P (1995) Standardization of spine BMD measurements. J Bone Miner Res 10:1602–1603PubMedGoogle Scholar
  21. 21.
    Genant HK, Grampp S, Gluer CC, Faulkner KG, Jergas M, Engelke K et al. (1994) Universal standardization for dual X-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res 9:1503–1514PubMedGoogle Scholar
  22. 22.
    Bruning PF, Pit MJ, de Jong-Bakker M, van den Ende A, Hart A, van Enk A (1990) Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer. Br J Cancer 61:308–310PubMedGoogle Scholar
  23. 23.
    Headley JA, Theriault RL, LeBlanc AD, Vassilopoulou-Sellin R, Hortobagyi GN (1998) Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy. Cancer Invest 16:6–11PubMedGoogle Scholar
  24. 24.
    Delmas PD, Fontana A (1998) Bone loss induced by cancer treatment and its management. Eur J Cancer 34:260–262CrossRefPubMedGoogle Scholar
  25. 25.
    Fogelman I (1992) Gonadotropin-releasing hormone agonists and the skeleton. Fertil Steril 57:715–724PubMedGoogle Scholar
  26. 26.
    Paoletti AM, Serra GG, Cagnacci A, Vacca AM, Guerriero S, Solla E, Melis GB (1996) Spontaneous reversibility of bone loss induced by gonadotropin-releasing hormone analog treatment. Fertil Steril 65:707–710PubMedGoogle Scholar
  27. 27.
    Taga M, Minaguchi H (1996) Reduction of bone mineral density by gonadotropin-releasing hormone agonist, nafarelin, is not completely reversible at 6 months after the cessation of administration. Acta Obstet Gynecol Scand 75:162–165PubMedGoogle Scholar
  28. 28.
    Powles TJ, McCloskey E, Paterson AH, Ashley S, Tidy VA, Nevantaus A et al. (1998) Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer. J Natl Cancer Inst 90:704–708CrossRefPubMedGoogle Scholar
  29. 29.
    Namer M, Jonat W, Kaufmann M, Blamey R, Cuzick J, Fogelman I et al. (2002) Survival data from the ZEBRA study. Ann Oncol 13 (suppl 5):38 (abstract 135P)Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2003

Authors and Affiliations

  • I. Fogelman
    • 1
  • G. M. Blake
    • 1
  • R. Blamey
    • 2
  • M. Palmer
    • 3
  • W. Sauerbrei
  • M. Schumacher
    • 4
  • D. Serin
    • 5
  • A. Stewart
    • 6
  • W. Wilpshaar
    • 3
  1. 1.Department of Nuclear MedicineGuy’s, Kings and St Thomas’ Hospital Medical SchoolLondonUK
  2. 2.Nottingham HospitalNottinghamUK
  3. 3.AstraZenecaMacclesfieldUK
  4. 4.Institute fur Medizinische Biometrie und InformatikUniversity HospitalFreiburgGermany
  5. 5.Clinic Sainte CatherineAvignonFrance
  6. 6.Christie HospitalManchesterUK

Personalised recommendations