Annals of Oncology 15:211-217, 2004
© 2004 European Society for Medical Oncology
Original Paper |
The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, ‘Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients’
Received 6 June 2003; revised 25 September 2003; accepted 6 October 2003;Background:
The impact of aromatase inhibitors (AIs) on non-cancer-related outcomes, which are known to be affected by oestrogens, has become increasingly important in postmenopausal women with hormone-dependent breast cancer. So far, data related to the effect of AIs on lipid profile in postmenopausal women is scarce. This study, as a companion substudy of an EORTC phase II trial (10951), evaluated the impact of exemestane, a steroidal aromatase inactivator, on the lipid profile of postmenopausal metastatic breast cancer (MBC) patients.
Patients and methods:
The EORTC trial 10951 randomised 122 postmenopausal breast cancer patients to exemestane (E) 25 mg (n = 62) or tamoxifen (T) 20 mg (n = 60) once daily as a first-line treatment in the metastatic setting. Exemestane showed promising results in all the primary efficacy end points of the trial (response rate, clinical benefit rate and response duration), and it was well tolerated with low incidence of serious toxicity. As a secondary end point of this phase II trial, serum triglycerides (TRG), high-density lipoprotein cholesterol (HDL), total cholesterol (TC), lipoprotein a (Lip a), and apolipoproteins (Apo) B and A1 were measured at baseline and while on therapy (at 8, 24 and 48 weeks) to assess the impact of exemestane and tamoxifen on serum lipid profiles. Of the 122 randomised patients, those who had baseline and at least one other lipid assessment are included in the present analysis. The patients who received concomitant drugs that could affect lipid profile are included only if these drugs were administered throughout the study treatment. Increase or decrease in lipid parameters within 20% of baseline were considered as non-significant and thus unchanged.
Results:
Seventy-two patients (36 in both arms) were included in the statistical analysis. The majority of patients had abnormal TC and normal TRG, HDL, Apo A1, Apo B and Lip a levels at baseline. Neither exemestane nor tamoxifen had adverse effects on TC, HDL, Apo A1, Apo B or Lip a levels at 8, 24 and 48 weeks of treatment. Exemestane and tamoxifen had opposite effects on TRG levels: exemestane lowered while tamoxifen increased TRG levels over time. There were too few patients with normal baseline TC and abnormal TRG, HDL, Apo A1, Apo B and Lip a levels to allow for assessment of E’s impact on these subsets. The atherogenic risk determined by Apo A1:Apo B and TC:HDL ratios remained unchanged throughout the treatment period in both the E and T arms.
Conclusions:
Overall, exemestane has no detrimental effect on cholesterol levels and the atherogenic indices, which are well-known risk factors for coronary artery disease. In addition, it has a beneficial effect on TRG levels. These data, coupled with E’s excellent efficacy and tolerability, support further exploration of its potential in the metastatic, adjuvant and chemopreventive setting.
1 Jules Bordet Institute, Brussels; 2 Algemeen Ziekenhuis Sint-Camillus/Sint-Augustinus, Wirlrijk; 8 Pharmacia, Diegem; 9 EORTC Data Center, Brussels; 10 Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium; 3 University Medical Center St Radboud, Nijmegen; 4 Leids Universitair Medisch Centrum, Afdeling Klinische Oncologie, Leiden, The Netherlands; 5 Western General Hospital, Edinburgh, UK; 6 British Columbia Cancer Agency, Vancouver, Canada; 7 Institute of Oncology, Ljubljana, Slovenia
Key words: breast cancer, exemestane, lipid profile
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Markopoulos, A. Polychronis, U. Dafni, D. Koukouras, V. Zobolas, E. Tzorakoleftherakis, G. Xepapadakis, and H. Gogas Lipid changes in breast cancer patients on exemestane treatment: final results of the TEAM Greek substudy Ann. Onc., January 1, 2009; 20(1): 49 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Paridaens, L. Y. Dirix, L. V. Beex, M. Nooij, D. A. Cameron, T. Cufer, M. J. Piccart, J. Bogaerts, and P. Therasse Phase III Study Comparing Exemestane With Tamoxifen As First-Line Hormonal Treatment of Metastatic Breast Cancer in Postmenopausal Women: The European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group J. Clin. Oncol., October 20, 2008; 26(30): 4883 - 4890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Ryan and P. E. Goss Adjuvant Hormonal Therapy in Peri- and Postmenopausal Breast Cancer Oncologist, July 1, 2006; 11(7): 718 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Banerjee, I. E. Smith, L. Folkerd, J. Iqbal, P. Barker, M. Dowsett, and On behalf of the IMPACT trialists Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial Ann. Onc., October 1, 2005; 16(10): 1632 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tabuchi, H. To, H. Sakaguchi, N. Goto, A. Takeuchi, S. Higuchi, and S. Ohdo Therapeutic Index by Combination of Adriamycin and Docetaxel Depends on Dosing Time in Mice Cancer Res., September 15, 2005; 65(18): 8448 - 8454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Wasan, P. E. Goss, P. H. Pritchard, L. Shepherd, M. J. Palmer, S. Liu, D. Tu, J. N. Ingle, M. Heath, D. DeAngelis, et al. The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L) Ann. Onc., May 1, 2005; 16(5): 707 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Strasser-Weippl and P. E. Goss Advances in Adjuvant Hormonal Therapy for Postmenopausal Women J. Clin. Oncol., March 10, 2005; 23(8): 1751 - 1759. [Full Text] [PDF]
|
|
|
|
|
|
L. Morales, D. Timmerman, P. Neven, M. L. Konstantinovic, A. Carbonez, S. Van Huffel, L. Ameye, C. Weltens, M.-R. Christiaens, I. Vergote, et al. Third generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients Ann. Onc., January 1, 2005; 16(1): 70 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Coombes, E. Hall, L. J. Gibson, R. Paridaens, J. Jassem, T. Delozier, S. E. Jones, I. Alvarez, G. Bertelli, O. Ortmann, et al. A Randomized Trial of Exemestane after Two to Three Years of Tamoxifen Therapy in Postmenopausal Women with Primary Breast Cancer N. Engl. J. Med., March 11, 2004; 350(11): 1081 - 1092. [Abstract] [Full Text] [PDF]
|
|