Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Jul;85(1):1–8. doi: 10.1054/bjoc.2001.1829

Adjuvant high-dose medroxyprogesterone acetate for early breast cancer: 13 years update in a multicentre randomized trial

C Focan 1, M Beauduin 2, E Salamon 3, J de Greve 4, G de Wasch 4, J P Lobelle 5, F Majois 2, A Tagnon 6, J Tytgat 7, S van Belle 8, R Vandervellen 9, A Vindevoghel 3; for the Adjuvant Breast Cancer Project Belgium
PMCID: PMC2363916  PMID: 11437394

Abstract

The authors updated their report on a randomized trial initiated in 1982 comparing, in early breast cancer, high-dose IM Medroxyprogesterone acetate (HD-MPA) adjuvant hormonotherapy during 6 months with no hormonotherapy; node-positive patients also received 6 courses of IV CMF (day 1, day 8; q.4 weeks). 246 node-negative (NN) and 270 node-positive (NP) patients had been followed for a median duration of 13 years. Previous results were confirmed in this analysis on mature data. In NN patients, relapse-free survival (RFS) was improved in the adjuvant hormonotherapy arm, regardless of age while overall survival (OAS) was also increased in younger (less then 50 years) patients. In the whole group of NP patients, no difference was seen regarding RFS or OAS. However, an age-dependant opposite effect was observed: younger patients (< 50) experienced a worse and significant outcome of relapse-free and overall survivals when receiving adjuvant HD-MPA while older patients (> = 50) enjoyed a significant improvement of their relapse-free survival. For both NN and NP patients, differences in overall survivals observed in older women with a shorter follow-up, were no longer detected. © 2001 Cancer Research Campaign http://www.bjcancer.com

Full Text

The Full Text of this article is available as a PDF (195.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alberts S. R., Ingle J. N., Roche P. R., Cha S. S., Wold L. E., Farr G. H., Jr, Krook J. E., Wieand H. S. Comparison of estrogen receptor determinations by a biochemical ligand-binding assay and immunohistochemical staining with monoclonal antibody ER1D5 in females with lymph node positive breast carcinoma entered on two prospective clinical trials. Cancer. 1996 Aug 15;78(4):764–772. doi: 10.1002/(SICI)1097-0142(19960815)78:4<764::AID-CNCR12>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  2. Andersen J. Determination of estrogen receptors in paraffin-embedded tissue. Techniques and the value in breast cancer treatment. Acta Oncol. 1992;31(6):611–627. doi: 10.3109/02841869209083843. [DOI] [PubMed] [Google Scholar]
  3. Andersson M., Kamby C., Jensen M. B., Mouridsen H., Ejlertsen B., Dombernowsky P., Rose C., Cold S., Overgaard M., Andersen J. Tamoxifen in high-risk premenopausal women with primary breast cancer receiving adjuvant chemotherapy. Report from the Danish Breast Cancer co-operative Group DBCG 82B Trial. Eur J Cancer. 1999 Nov;35(12):1659–1666. doi: 10.1016/s0959-8049(99)00141-0. [DOI] [PubMed] [Google Scholar]
  4. Beex L., Burghouts J., van Turnhout J., Breed W., Hillen H., Holdrinet A., Boetius G., Hoogendoorn G., Doesburg W., Verhulst M. Oral versus im administration of high-dose medroxyprogesterone acetate in pretreated patients with advanced breast cancer. Cancer Treat Rep. 1987 Dec;71(12):1151–1156. [PubMed] [Google Scholar]
  5. Blossey H. C., Wander H. E., Koebberling J., Nagel G. A. Pharmacokinetic and pharmacodynamic basis for the treatment of metastatic breast cancer with high-dose medroxyprogesterone acetate. Cancer. 1984 Sep 15;54(6 Suppl):1208–1215. doi: 10.1002/1097-0142(19840915)54:1+<1208::aid-cncr2820541319>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  6. Bramwell V. H., Pritchard K. I. Tamoxifen added to adjuvant chemotherapy in premenopausal women with early breast cancer: is it standard practice or still a subject for study? Eur J Cancer. 1999 Nov;35(12):1625–1627. doi: 10.1016/s0959-8049(99)00204-x. [DOI] [PubMed] [Google Scholar]
  7. Canney P. A., Dowsett M., Priestman T. J. The pharmacokinetics of medroxyprogesterone acetate following two different loading dose schedules in advanced carcinoma of the breast. Br J Cancer. 1988 Jul;58(1):73–76. doi: 10.1038/bjc.1988.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Castiglione-Gertsch M., Pampallona S., Varini M., Cavalli F., Brunner K., Senn H. J., Goldhirsch A., Metzger U. Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate? Ann Oncol. 1993 Nov;4(9):735–740. doi: 10.1093/oxfordjournals.annonc.a058657. [DOI] [PubMed] [Google Scholar]
  9. Cavalli F., Goldhirsch A., Jungi F., Martz G., MermillodB, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol. 1984 May;2(5):414–419. doi: 10.1200/JCO.1984.2.5.414. [DOI] [PubMed] [Google Scholar]
  10. Etienne M. C., Milano G., Frenay M., Renee N., Francois E., Thyss A., Schneider M., Namer M. Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients. J Clin Oncol. 1992 Jul;10(7):1176–1182. doi: 10.1200/JCO.1992.10.7.1176. [DOI] [PubMed] [Google Scholar]
  11. Fisher B., Dignam J., Wolmark N., DeCillis A., Emir B., Wickerham D. L., Bryant J., Dimitrov N. V., Abramson N., Atkins J. N. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997 Nov 19;89(22):1673–1682. doi: 10.1093/jnci/89.22.1673. [DOI] [PubMed] [Google Scholar]
  12. Focan C., Baudoux A., Beauduin M., Bunescu U., Dehasque N., Dewasch L., Lobelle J. P., Longeval E., Majois F., Mazy V. Adjuvant treatment with high dose medroxyprogesterone acetate in node-negative early breast cancer. A 3-year interim report on a randomized trial (I). Acta Oncol. 1989;28(2):237–240. doi: 10.3109/02841868909111254. [DOI] [PubMed] [Google Scholar]
  13. Focan C., Baudoux A., Beauduin M., Bunescu U., Dehasque N., Dewasch L., Lobelle J. P., Longeval E., Majois F., Salamon E. Improvement of hematological and general tolerance to CMF by high-dose medroxyprogesterone acetate (HD-MPA) adjuvant treatment for primary node positive breast cancer (analysis of 100 patients). Anticancer Res. 1986 Sep-Oct;6(5):1095–1099. [PubMed] [Google Scholar]
  14. Gill P. G., Gebski V., Snyder R., Burns I., Levi J., Byrne M., Coates A. Randomized comparison of the effects of tamoxifen, megestrol acetate, or tamoxifen plus megestrol acetate on treatment response and survival in patients with metastatic breast cancer. Ann Oncol. 1993 Nov;4(9):741–744. doi: 10.1093/oxfordjournals.annonc.a058658. [DOI] [PubMed] [Google Scholar]
  15. Hryniuk W., Levine M. N. Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol. 1986 Aug;4(8):1162–1170. doi: 10.1200/JCO.1986.4.8.1162. [DOI] [PubMed] [Google Scholar]
  16. Hupperets P. S., Wils J., Volovics L., Schouten L., Fickers M., Bron H., Schouten H. C., Jager J., Smeets J., de Jong J. Adjuvant chemohormonal therapy with cyclophosphamide, doxorubicin and 5-fluorouracil (CAF) with or without medroxyprogesterone acetate for node-positive breast cancer patients. Ann Oncol. 1993 Apr;4(4):295–301. doi: 10.1093/oxfordjournals.annonc.a058485. [DOI] [PubMed] [Google Scholar]
  17. Hyder S. M., Murthy L., Stancel G. M. Progestin regulation of vascular endothelial growth factor in human breast cancer cells. Cancer Res. 1998 Feb 1;58(3):392–395. [PubMed] [Google Scholar]
  18. Løber J., Rose C., Salimtschik M., Mouridsen H. T. Treatment of advanced breast cancer with progestins. Acta Obstet Gynecol Scand Suppl. 1981;101:39–46. doi: 10.3109/00016348109157810. [DOI] [PubMed] [Google Scholar]
  19. Martoni A., Longhi A., Canova N., Pannuti F. High-dose medroxyprogesterone acetate versus oophorectomy as first-line therapy of advanced breast cancer in premenopausal patients. Oncology. 1991;48(1):1–6. doi: 10.1159/000226884. [DOI] [PubMed] [Google Scholar]
  20. Muss H. B., Case L. D., Capizzi R. L., Cooper M. R., Cruz J., Jackson D., Richards F., 2nd, Powell B. L., Spurr C. L., White D. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1990 Nov;8(11):1797–1805. doi: 10.1200/JCO.1990.8.11.1797. [DOI] [PubMed] [Google Scholar]
  21. Muss H. B., Wells H. B., Paschold E. H., Black W. R., Cooper M. R., Capizzi R. L., Christian R., Cruz J. M., Jackson D. V., Powell B. L. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association. J Clin Oncol. 1988 Jul;6(7):1098–1106. doi: 10.1200/JCO.1988.6.7.1098. [DOI] [PubMed] [Google Scholar]
  22. Pannuti F., Martoni A., Cilenti G., Camaggi C. M., Fruet F. Adjuvant therapy for operable breast cancer with medroxyprogesterone acetate alone in postmenopausal patients or in combination with CMF in premenopausal patients. Eur J Cancer Clin Oncol. 1988 Mar;24(3):423–429. doi: 10.1016/s0277-5379(98)90012-8. [DOI] [PubMed] [Google Scholar]
  23. Paridaens R., Becquart D., Michel J., Vanderlinden B., Longueville J., Majois F., Beauduin M., Focan C., Wildiers J., Bernheim J. Oral versus intramuscular high-dose medroxyprogesterone acetate (HD-MPA) in advanced breast cancer. A randomized study of the Belgian Society of Medical Oncology. Anticancer Res. 1986 Sep-Oct;6(5):1089–1094. [PubMed] [Google Scholar]
  24. Pertschuk L. P., Kim Y. D., Axiotis C. A., Braverman A. S., Carter A. C., Eisenberg K. B., Braithwaite L. V. Estrogen receptor immunocytochemistry: the promise and the perils. J Cell Biochem Suppl. 1994;19:134–137. [PubMed] [Google Scholar]
  25. Rubens R. D. Towards improved endocrine therapy for advanced breast cancer. Ann Oncol. 1993 Nov;4(9):712–713. doi: 10.1093/oxfordjournals.annonc.a058650. [DOI] [PubMed] [Google Scholar]
  26. Tamassia V., Battaglia A., Ganzina F., Isetta A. M., Sacchetti G., Cavalli F., Goldhirsch A., Brunner K., Bernardo G., Robustelli della Cuna G. Pharmacokinetic approach to the selection of dose schedules for medroxyprogesterone acetate in clinical oncology. Cancer Chemother Pharmacol. 1982;8(2):151–156. doi: 10.1007/BF00255475. [DOI] [PubMed] [Google Scholar]
  27. Tchekmedyian N. S., Tait N., Aisner J. High-dose megestrol acetate in the treatment of postmenopausal women with advanced breast cancer. Semin Oncol. 1986 Dec;13(4 Suppl 4):20–25. [PubMed] [Google Scholar]
  28. Wils J. A. Myeloprotective effect of high dose medroxyprogesterone acetate (MPA). Chemioterapia. 1988 Feb;7(1):60–62. [PubMed] [Google Scholar]
  29. van Veelen H., Willemse P. H., Sleijfer D. T., Sluiter W. J., Doorenbos H. Endocrine effects of medroxyprogesterone acetate: relation between plasma levels and suppression of adrenal steroids in patients with breast cancer. Cancer Treat Rep. 1985 Sep;69(9):977–983. [PubMed] [Google Scholar]
  30. van Veelen H., Willemse P. H., Tjabbes T., Schweitzer M. J., Sleijfer D. T. Oral high-dose medroxyprogesterone acetate versus tamoxifen. A randomized crossover trial in postmenopausal patients with advanced breast cancer. Cancer. 1986 Jul 1;58(1):7–13. doi: 10.1002/1097-0142(19860701)58:1<7::aid-cncr2820580103>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES