| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Academic Departments of Biochemistry [C. H-W., J. S., J. I., M. D.], Radiotherapy [G. R.], Surgery [N. S.], Histopathology [N. N.], and Statistics [R. A.], Royal Marsden Hospital, London SW3 6JJ, United Kingdom
The aromatase enzyme converts androgens to estrogens and is the therapeutic target for aromatase inhibitors in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Third-generation inhibitors such as letrozole are being considered as potential prophylactic agents for breast cancer. The rationale for their preventive application would be aided by knowledge of their effects on the normal breast and on other estrogen-dependent processes such as bone and lipid metabolism. Thirty-two women without active breast disease were recruited to 3-month treatment with letrozole (2.5 mg/day). Core-cut biopsies from the breast and blood samples were collected before and at the end of treatment. Plasma estradiol levels were markedly suppressed in all but two patients, who were excluded from the efficacy assessment. There was no significant change in the proliferation marker Ki67 (mean change, -23%; 95% confidence interval, -50% to +23%) or estrogen receptor in breast epithelial cells with treatment. Similarly, there were no significant changes in plasma levels of insulin-like growth factor I or lipid profiles. However, there was a significant increase (25%) in the levels of the bone resorption marker C-telopeptide crosslinks (CTx). We conclude that any prophylactic effect of letrozole is not likely to be dependent on antiproliferative effects on normal breast. Studies in healthy patients will need to recognize the potential for enhanced bone resorption.
This article has been cited by other articles:
|
|
 |
|
  G. A. Colditz and D. M. Winn Criteria for the Evaluation of Large Cohort Studies: An Application to the Nurses' Health Study J Natl Cancer Inst, July 2, 2008; 100(13): 918 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Banerjee, S. Pancholi, R. A'Hern, Z. Ghazoui, I. E. Smith, M. Dowsett, and L.-A. Martin The Effects of Neoadjuvant Anastrozole and Tamoxifen on Circulating Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor 1 in Breast Cancer Clin. Cancer Res., May 1, 2008; 14(9): 2656 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kendall, H. Anderson, A. K. Dunbier, A. Mackay, T. Dexter, A. Urruticoechea, C. Harper-Wynne, and M. Dowsett Impact of Estrogen Deprivation on Gene Expression Profiles of Normal Postmenopausal Breast Tissue In vivo Cancer Epidemiol. Biomarkers Prev., April 1, 2008; 17(4): 855 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Arun, V. Valero, C. Logan, K. Broglio, E. Rivera, A. Brewster, G. Yin, M. Green, H. Kuerer, Y. Gong, et al. Comparison of Ductal Lavage and Random Periareolar Fine Needle Aspiration as Tissue Acquisition Methods in Early Breast Cancer Prevention Trials Clin. Cancer Res., August 15, 2007; 13(16): 4943 - 4948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Chien and P. E. Goss Aromatase Inhibitors and Bone Health in Women With Breast Cancer J. Clin. Oncol., November 20, 2006; 24(33): 5305 - 5312. [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Perez Appraising Adjuvant Aromatase Inhibitor Therapy Oncologist, November 1, 2006; 11(10): 1058 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kendall and M. Dowsett Novel concepts for the chemoprevention of breast cancer through aromatase inhibition. Endocr. Relat. Cancer, September 1, 2006; 13(3): 827 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. U Buzdar and J. F. Robertson Fulvestrant: Pharmacologic Profile Versus Existing Endocrine Agents for the Treatment of Breast Cancer Ann. Pharmacother., September 1, 2006; 40(9): 1572 - 1582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M K Simick and L Lilge Optical transillumination spectroscopy to quantify parenchymal tissue density: an indicator for breast cancer risk Br. J. Radiol., November 1, 2005; 78(935): 1009 - 1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Urruticoechea, I. E. Smith, and M. Dowsett Proliferation Marker Ki-67 in Early Breast Cancer J. Clin. Oncol., October 1, 2005; 23(28): 7212 - 7220. [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]
|
|
|
|
|
|
S A Khan, D Bhandare, and R T Chatterton Jr The local hormonal environment and related biomarkers in the normal breast Endocr. Relat. Cancer, September 1, 2005; 12(3): 497 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Lonning, J. Geisler, L. E. Krag, B. Erikstein, Y. Bremnes, A. I. Hagen, E. Schlichting, E. A. Lien, E. S. Ofjord, J. Paolini, et al. Effects of Exemestane Administered for 2 Years Versus Placebo on Bone Mineral Density, Bone Biomarkers, and Plasma Lipids in Patients With Surgically Resected Early Breast Cancer J. Clin. Oncol., August 1, 2005; 23(22): 5126 - 5137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C J Fabian, B F Kimler, M S Mayo, and S A Khan Breast-tissue sampling for risk assessment and prevention Endocr. Relat. Cancer, June 1, 2005; 12(2): 185 - 213. [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]
|
|
|
|
|
|
Q. J. Khan, B. F. Kimler, J. Clark, T. Metheny, C. M. Zalles, and C. J. Fabian Ki-67 Expression in Benign Breast Ductal Cells Obtained by Random Periareolar Fine Needle Aspiration Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 786 - 789. [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]
|
|
|
|
|
|
M. Dowsett, I. E. Smith, S. R. Ebbs, J. M. Dixon, A. Skene, C. Griffith, I. Boeddinghaus, J. Salter, S. Detre, M. Hills, et al. Short-Term Changes in Ki-67 during Neoadjuvant Treatment of Primary Breast Cancer with Anastrozole or Tamoxifen Alone or Combined Correlate with Recurrence-Free Survival Clin. Cancer Res., January 15, 2005; 11(2): 951s - 958s. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Stearns, A. Gallagher, C. G. Kleer, B. Singh, M. Freedman, B. R. Haddad, C. Isaacs, R. Warren, M. Brown, J. Cullen, et al. A Pilot Study to Establish a Clinical Model to Perform Phase II Studies of Breast Cancer Chemopreventive Agents in Women at High Risk with Biomarkers as Surrogate Endpoints for Activity Clin. Cancer Res., December 15, 2004; 10(24): 8332 - 8340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Goss, S. Qi, A. M. Cheung, H. Hu, M. Mendes, and K. P. H. Pritzker Effects of the Steroidal Aromatase Inhibitor Exemestane and the Nonsteroidal Aromatase Inhibitor Letrozole on Bone and Lipid Metabolism in Ovariectomized Rats Clin. Cancer Res., September 1, 2004; 10(17): 5717 - 5723. [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]
|
|
|
|
|
|
P. E. Goss and K. Strasser-Weippl Prevention Strategies with Aromatase Inhibitors Clin. Cancer Res., January 1, 2004; 10(1): 372S - 379S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Goss, J. N. Ingle, S. Martino, N. J. Robert, H. B. Muss, M. J. Piccart, M. Castiglione, D. Tu, L. E. Shepherd, K. I. Pritchard, et al. A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer N. Engl. J. Med., November 6, 2003; 349(19): 1793 - 1802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. E. Smith and M. Dowsett Aromatase Inhibitors in Breast Cancer N. Engl. J. Med., June 12, 2003; 348(24): 2431 - 2442. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
