Breast cancer is the most common cancer diagnosed and the second leading cause of cancer-related death in women. The majority of breast cancers diagnosed in postmenopausal women are hormone receptor positive and involve therapy with hormonal agents. Tamoxifen, a selective estrogen-receptor modulator, has been the mainstay of hormonal therapy since the 1970s. The more recent approval and success of aromatase inhibitors, such as anastrozole, letrozole, and exemestane, have seen these agents move to the front line of therapy for postmenopausal women with hormone-positive breast cancer in the adjuvant and metastatic settings. Fulvestrant, a selective estrogen receptor— downregulator, provides an additional hormonal therapy with a novel mechanism of action. This article reviews the current literature available regarding the use of these agents for postmenopausal women with early stage or advanced breast cancer.
American Cancer Society.Cancer Facts & Figures 2007. http://www.cancer.org/docroot/STT/content/STT_1x_Cancer_Facts__Figures_2007.asp. Accessed November 10, 2007.
2.
Rugo HSHormonal therapy for advanced breast cancer. Hematol Oncol Clin North Am. 2007;21:273-291.
3.
Ingle JN, Ahmann DL, GreenSJ, et al. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N Engl J Med. 1981;304:16-21.
4.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. Lancet. 2005;365:1687-1717.
5.
Fisher B., Costantino JP, Redmond CK, et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J Natl Cancer Inst. 1994;86:527-537.
6.
Hayes DF, Van Zyl JA, Hacking A., et al. Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol. 1995;13:2556-2566.
7.
Buzdar AU, Jones SE, Vogel CL, Wolter J., Plourde P., Webster A.A Phase III trial comparing anastrozole (1 and 10 milligrams), a potent and selective aromatase inhibitor, with megestrol acetate in postmenopausal women with advanced breast carcinoma. Cancer. 1997 ;79:730-739.
8.
Jonat W., Howell A., Blomquist C., et al. A randomized trial comparing two doses of the new selective aromatase inhibitor (Arimidex) with megestrol acetate in postmenopausal patients with advanced breast cancer. Eur J Cancer. 1996;32:404-412.
9.
Buzdar AU, Jonat W., Howell A., et al. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma. Cancer. 1998;83:1142-1152.
10.
Dombernowsky P., Smith I., Falkson G., et al. Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetateJ Clin Oncol. 1998;16:453-461.
11.
Kaufmann M. , Bajetta E., Dirix LY, et al. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol. 2000;18:1399-1411.
12.
Nabholtz JM , Buzdar A., Pollak M., et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol. 2000;18:3758-3767.
13.
Mouridsen H. , Gershanovich M., Sun Y., et al. Phase III Study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol. 2003;21:2101-2109.
14.
The ATAC (Arimidex, Tamoxifen Alone or in Combination) Trialists' Group.Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial . Lancet. 2002;359:2131-2139.
15.
The ATAC Trialists' Group.Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005; 365:60-62.
16.
The Breast International Group (BIG) 1-98 Collaborative Group.A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353:2747-2757.
17.
Coombes CR, Hall E., Gibson LJ, 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. 2004;350:1081-1092.
18.
Boccardo F. , Rubagotti A., Puntoni M., et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole trial. J Clin Oncol. 2005;23: 5138-5147.
19.
Kaufman M., Jonat W., Hilfrich J., et al. Improved overall survival in postmenopausal women with early breast cancer after anastrozole initiated after treatment with tamoxifen compared with continued tamoxifen: the ARNO 95 study. J Clin Oncol . 2007;25: 2664-2670.
20.
Jakesz R., Jonat W., Gnant M., et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366:455-462.
21.
Goss PE, Ingle JN, Martino S., 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. 2003;349:1793-1802.
22.
Goss PE, Ingle JN, Martino S., et al. Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada clinical trials group MA.17. J Clin Oncol. 2007;25:2006-2011.
23.
National Comprehensive Cancer Network.National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Breast Cancer. http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf . Accessed November 1, 2007.
24.
Howell A., Robertson JF, Abram P., et al. Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. J Clin Oncol. 2004;22:1605-1613.
25.
Howell A., Pippen J., Elledge RM, et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma. Cancer. 2005;104:236-239.
26.
Jordan, VCMetabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Breast Cancer Res Treatment. 1982;2:123-138.
27.
Lien EA, Solheim E., Lea OA, Lundgren S., Kvinnsland S., Ueland PMDistribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer . 1989;49:2175-2183.
28.
Stearns V., Johnson MD, Rae JM, et al. Active tamoxifen metabolites plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst. 2003;95:1758-1764.
29.
Desta Z., Ward BA, Soukhova NV, Flockhart DAComprehensive evaluation of tamoxifen sequential bio-transformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6 . J Pharmacol Exp Ther. 2004;310:1062-1075.
30.
Johnson MD, Zuo H., Lee KH, et al. Pharmacological characterization of 4-hydroxy-N-desmethyltamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat. 2004;85:151-159.
31.
Saschse C., Brockmoller J., Hildebrand M., Muller K., Roots I.Correctness of prediction of the CYP2D6 phenotype confirmed by genotyping 47 intermediate and poor metabolizers of debrisoquine. Pharmacogenetics . 1998;8:181-185.
32.
Johansson I. , Oscarson M., Yue QY, Bertilsson L., Sjogvist F., Ingelman-Sundberg M.Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 gene present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol. 1994;46: 452-459.
33.
Yoon YR, Cha IJ, Shon JH, et al. Relationship of paroxetine disposition to metoprolol metabolic ratio and CYP2D6*10 genotype of Korean subjects. Clin Pharmacol Ther. 2000;67: 567-576.
34.
Roh HK, Dahl ML, Johansson I., Ingelman-Sundberg M., Cha YN, Bertilsson L.Debrisoquine and S-mephenytoin hydroxylation phenotypes and genotypes in a Korean population. Pharmacogenetics. 1996;6:441-447.
35.
Paik S., Tang G., Shak S., et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor- positive breast cancer. J Clin Oncol. 2006;24:3726-3734.
