FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 348:2431-2442 June 12, 2003 Number 24 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text PDF PDA Full Text Purchase this article Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

The third-generation aromatase inhibitors provide novel approaches to the endocrine treatment of breast cancer. These drugs are effectively challenging tamoxifen, the previous gold standard of care,^{1,2,3,4,5,6,7,8,9,10,11,12,13} for use in postmenopausal patients with estrogen-receptor–positive cancers, who make up the majority of patients with breast cancer. These agents are also being considered for use in chemoprevention, a strategy in which tamoxifen has already been shown to reduce the incidence of breast cancer.^14,15 In this article, we review the current role of aromatase inhibitors and assess their potential for clinical use. Other reviews that may be of interest to specialists are also available.^16,17

Background

Mechanisms of Action

. . . [Full Text of this Article]

Sources of Aromatase

Aromatase Inhibition in Premenopausal Women

Clinical Development and Pharmacology

Pharmacokinetics

Comparative Pharmacologic Efficacy

Current Clinical Role

Advanced Disease

            First-Line Therapy

            Second-Line Therapy

Early Disease

            Neoadjuvant Therapy

            Adjuvant Therapy

Adverse Effects and Long-Term Risks and Benefits

Skeletal Effects

Cardiovascular Effects

Effects on Cognition

Hormone-Replacement Therapy and Adjuvant Breast-Cancer Therapy

Chemoprevention

Other Issues

Is There a Best Third-Generation Aromatase Inhibitor?

Aromatase Inhibitors in Combination with Chemotherapy

Conclusions

Source Information

From the Royal Marsden Hospital and Institute of Cancer Research, London.

Address reprint requests to Dr. Smith at the Breast Unit, Royal Marsden Hospital, Fulham Rd., London SW3 6JJ, United Kingdom, or at ian.smith@rmh.nthames.nhs.uk.

Related Letters:

Aromatase Inhibitors in Breast Cancer
Forrest A. R.W.
Extract | Full Text | PDF  
N Engl J Med 2003; 349:1090, Sep 11, 2003. Correspondence

This article has been cited by other articles:

• Odawara, H., Iwasaki, T., Horiguchi, J., Rokutanda, N., Hirooka, K., Miyazaki, W., Koibuchi, Y., Shimokawa, N., Iino, Y., Takeyoshi, I., Koibuchi, N. (2009). Activation of Aromatase Expression by Retinoic Acid Receptor-related Orphan Receptor (ROR) {alpha} in Breast Cancer Cells: IDENTIFICATION OF A NOVEL ROR RESPONSE ELEMENT. J. Biol. Chem. 284: 17711-17719 [Abstract] [Full Text]  
• Giobbie-Hurder, A., Price, K. N, Gelber, R. D (2009). Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer. Clin Trials 6: 272-287 [Abstract]  
• Banerjee, S., Zvelebil, M., Furet, P., Mueller-Vieira, U., Evans, D. B., Dowsett, M., Martin, L.-A. (2009). The Vascular Endothelial Growth Factor Receptor Inhibitor PTK787/ZK222584 Inhibits Aromatase. Cancer Res. 69: 4716-4723 [Abstract] [Full Text]  
• Woodfield, G. W., Hitchler, M. J., Chen, Y., Domann, F. E., Weigel, R. J. (2009). Interaction of TFAP2C with the Estrogen Receptor-{alpha} Promoter Is Controlled by Chromatin Structure. Clin. Cancer Res. 15: 3672-3679 [Abstract] [Full Text]  
• Chen, Y., Guggisberg, N., Jorda, M., Gonzalez-Angulo, A., Hennessy, B., Mills, G. B., Tan, C.-K., Slingerland, J. M. (2009). Combined Src and Aromatase Inhibition Impairs Human Breast Cancer Growth In vivo and Bypass Pathways Are Activated in AZD0530-Resistant Tumors. Clin. Cancer Res. 15: 3396-3405 [Abstract] [Full Text]  
• Saeki, T., Noguchi, S., Aogi, K., Inaji, H., Tabei, T., Ikeda, T. (2009). Evaluation of the safety and tolerability of oral TAS-108 in postmenopausal patients with metastatic breast cancer. Ann Oncol 20: 868-873 [Abstract] [Full Text]  
• Miller, W. R., Larionov, A., Renshaw, L., Anderson, T. J., Walker, J. R., Krause, A., Sing, T., Evans, D. B., Dixon, J. M. (2009). Gene Expression Profiles Differentiating Between Breast Cancers Clinically Responsive or Resistant to Letrozole. JCO 27: 1382-1387 [Abstract] [Full Text]  
• Sowden, E., Evans, B., Greenbank, C. M., Bukhari, M., Halsey, J. P. (2009). Assessment of the impact of new UK guidelines on the management of aromatase inhibitor-associated bone loss. Rheumatology (Oxford) 48: 197-198 [Full Text]  
• Generali, D., Buffa, F. M., Berruti, A., Brizzi, M. P., Campo, L., Bonardi, S., Bersiga, A., Allevi, G., Milani, M., Aguggini, S., Papotti, M., Dogliotti, L., Bottini, A., Harris, A. L., Fox, S. B. (2009). Phosphorylated ER{alpha}, HIF-1{alpha}, and MAPK Signaling As Predictors of Primary Endocrine Treatment Response and Resistance in Patients With Breast Cancer. JCO 27: 227-234 [Abstract] [Full Text]  
• Ruddy, K., Mayer, E., Partridge, A. (2009). Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin 59: 56-66 [Abstract] [Full Text]  
• Partridge, A. H., Kato, P. M., DeMichele, A. (2009). Adherence to Oral Cancer Therapies: Challenges and Opportunities. Am Soc Clin Oncol Ed Book 2009: 124-128 [Abstract] [Full Text]  
• van der Deure, W. M., Friesema, E. C. H., de Jong, F. J., de Rijke, Y. B., de Jong, F. H., Uitterlinden, A. G., Breteler, M. M. B., Peeters, R. P., Visser, T. J. (2008). Organic Anion Transporter 1B1: An Important Factor in Hepatic Thyroid Hormone and Estrogen Transport and Metabolism. Endocrinology 149: 4695-4701 [Abstract] [Full Text]  
• Mao, C., Patterson, N. M., Cherian, M. T., Aninye, I. O., Zhang, C., Montoya, J. B., Cheng, J., Putt, K. S., Hergenrother, P. J., Wilson, E. M., Nardulli, A. M., Nordeen, S. K., Shapiro, D. J. (2008). A New Small Molecule Inhibitor of Estrogen Receptor {alpha} Binding to Estrogen Response Elements Blocks Estrogen-dependent Growth of Cancer Cells. J. Biol. Chem. 283: 12819-12830 [Abstract] [Full Text]  
• Banerjee, S., Pancholi, S., A'Hern, R., Ghazoui, Z., Smith, I. E., Dowsett, M., Martin, L.-A. (2008). 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. 14: 2656-2663 [Abstract] [Full Text]  
• Generali, D., Fox, S. B., Brizzi, M. P., Allevi, G., Bonardi, S., Aguggini, S., Milani, M., Bersiga, A., Campo, L., Dionisio, R., Vergoni, F., Giardini, R., Dogliotti, L., Bottini, A., Harris, A. L., Berruti, A. (2008). Down-Regulation of Phosphatidylinositol 3'-Kinase/AKT/Molecular Target of Rapamycin Metabolic Pathway by Primary Letrozole-Based Therapy in Human Breast Cancer. Clin. Cancer Res. 14: 2673-2680 [Abstract] [Full Text]  
• Kendall, A., Anderson, H., Dunbier, A. K., Mackay, A., Dexter, T., Urruticoechea, A., Harper-Wynne, C., Dowsett, M. (2008). Impact of Estrogen Deprivation on Gene Expression Profiles of Normal Postmenopausal Breast Tissue In vivo. Cancer Epidemiol. Biomarkers Prev. 17: 855-863 [Abstract] [Full Text]  
• Dirix, L. Y., Ignacio, J., Nag, S., Bapsy, P., Gomez, H., Raghunadharao, D., Paridaens, R., Jones, S., Falcon, S., Carpentieri, M., Abbattista, A., Lobelle, J.-P. (2008). Treatment of Advanced Hormone-Sensitive Breast Cancer in Postmenopausal Women With Exemestane Alone or in Combination With Celecoxib. JCO 26: 1253-1259 [Abstract] [Full Text]  
• Trinkaus, M., Chin, S., Wolfman, W., Simmons, C., Clemons, M. (2008). Should Urogenital Atrophy in Breast Cancer Survivors Be Treated with Topical Estrogens?. The Oncologist 13: 222-231 [Abstract] [Full Text]  
• Parton, M., Smith, I. E. (2008). Controversies in the Management of Patients With Breast Cancer: Adjuvant Endocrine Therapy in Premenopausal Women. JCO 26: 745-752 [Full Text]  
• Dowsett, M. (2008). Factors Predicting Response and Resistance to Endocrine Therapy of Breast Cancer. Am Soc Clin Oncol Ed Book 2008: 14-17 [Abstract] [Full Text]  
• Mah, V., Seligson, D. B., Li, A., Marquez, D. C., Wistuba, I. I., Elshimali, Y., Fishbein, M. C., Chia, D., Pietras, R. J., Goodglick, L. (2007). Aromatase Expression Predicts Survival in Women with Early-Stage Non Small Cell Lung Cancer. Cancer Res. 67: 10484-10490 [Abstract] [Full Text]  
• Varricchio, L., Migliaccio, A., Castoria, G., Yamaguchi, H., de Falco, A., Di Domenico, M., Giovannelli, P., Farrar, W., Appella, E., Auricchio, F. (2007). Inhibition of Estradiol Receptor/Src Association and Cell Growth by an Estradiol Receptor {alpha} Tyrosine-Phosphorylated Peptide. Mol Cancer Res 5: 1213-1221 [Abstract] [Full Text]  
• Miki, Y., Suzuki, T., Tazawa, C., Yamaguchi, Y., Kitada, K., Honma, S., Moriya, T., Hirakawa, H., Evans, D. B., Hayashi, S.-i., Ohuchi, N., Sasano, H. (2007). Aromatase Localization in Human Breast Cancer Tissues: Possible Interactions between Intratumoral Stromal and Parenchymal Cells. Cancer Res. 67: 3945-3954 [Abstract] [Full Text]  
• Stanway, S. J., Delavault, P., Purohit, A., Woo, L. W. L., Thurieau, C., Potter, B. V. L., Reed, M. J. (2007). Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer. The Oncologist 12: 370-374 [Abstract] [Full Text]  
• Hong, Y., Yu, B., Sherman, M., Yuan, Y.-C., Zhou, D., Chen, S. (2007). Molecular Basis for the Aromatization Reaction and Exemestane-Mediated Irreversible Inhibition of Human Aromatase. Mol. Endocrinol. 21: 401-414 [Abstract] [Full Text]  
• Perey, L, Paridaens, R, Hawle, H, Zaman, K, Nole, F, Wildiers, H, Fiche, M, Dietrich, D, Clement, P, Koberle, D, Goldhirsch, A, Thurlimann, B (2007). Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol 18: 64-69 [Abstract] [Full Text]  
• Oktay, K., Hourvitz, A., Sahin, G., Oktem, O., Safro, B., Cil, A., Bang, H. (2006). Letrozole Reduces Estrogen and Gonadotropin Exposure in Women with Breast Cancer Undergoing Ovarian Stimulation before Chemotherapy. J. Clin. Endocrinol. Metab. 91: 3885-3890 [Abstract] [Full Text]  
• Van Poznak, C. H., Hayes, D. F. (2006). Aromatase inhibitors for the treatment of breast cancer: is tamoxifen of historical interest only?. JNCI J Natl Cancer Inst 98: 1261-1263 [Full Text]  
• Lupu, R., Menendez, J. A. (2006). Targeting Fatty Acid Synthase in Breast and Endometrial Cancer: An Alternative to Selective Estrogen Receptor Modulators?. Endocrinology 147: 4056-4066 [Abstract] [Full Text]  
• Kendall, A., Dowsett, M., Folkerd, E., Smith, I. (2006). Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors. Ann Oncol 17: 584-587 [Abstract] [Full Text]  
• Come, S. E. (2006). A 62-Year-Old Woman With a New Diagnosis of Breast Cancer. JAMA 295: 1434-1442 [Full Text]  
• Stanway, S. J., Purohit, A., Woo, L.W. L., Sufi, S., Vigushin, D., Ward, R., Wilson, R. H., Stanczyk, F. Z., Dobbs, N., Kulinskaya, E., Elliott, M., Potter, B. V.L., Reed, M. J., Coombes, R. C. (2006). Phase I Study of STX 64 (667 Coumate) in Breast Cancer Patients: The First Study of a Steroid Sulfatase Inhibitor. Clin. Cancer Res. 12: 1585-1592 [Abstract] [Full Text]  
• Prentice, R. L., Caan, B., Chlebowski, R. T., Patterson, R., Kuller, L. H., Ockene, J. K., Margolis, K. L., Limacher, M. C., Manson, J. E., Parker, L. M., Paskett, E., Phillips, L., Robbins, J., Rossouw, J. E., Sarto, G. E., Shikany, J. M., Stefanick, M. L., Thomson, C. A., Van Horn, L., Vitolins, M. Z., Wactawski-Wende, J., Wallace, R. B., Wassertheil-Smoller, S., Whitlock, E., Yano, K., Adams-Campbell, L., Anderson, G. L., Assaf, A. R., Beresford, S. A. A., Black, H. R., Brunner, R. L., Brzyski, R. G., Ford, L., Gass, M., Hays, J., Heber, D., Heiss, G., Hendrix, S. L., Hsia, J., Hubbell, F. A., Jackson, R. D., Johnson, K. C., Kotchen, J. M., LaCroix, A. Z., Lane, D. S., Langer, R. D., Lasser, N. L., Henderson, M. M. (2006). Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295: 629-642 [Abstract] [Full Text]  
• Honma, N., Takubo, K., Sawabe, M., Arai, T., Akiyama, F., Sakamoto, G., Utsumi, T., Yoshimura, N., Harada, N. (2006). Estrogen-Metabolizing Enzymes in Breast Cancers from Women over the Age of 80 Years. J. Clin. Endocrinol. Metab. 91: 607-613 [Abstract] [Full Text]  
• Smith, I., Chua, S. (2006). Medical treatment of early breast cancer. II: endocrine therapy. BMJ 332: 101-103 [Full Text]  
• The Breast International Group (BIG) 1-98 Collabor, (2005). A Comparison of Letrozole and Tamoxifen in Postmenopausal Women with Early Breast Cancer. NEJM 353: 2747-2757 [Abstract] [Full Text]  
• Dowsett, M., Cuzick, J., Wale, C., Howell, T., Houghton, J., Baum, M. (2005). Retrospective Analysis of Time to Recurrence in the ATAC Trial According to Hormone Receptor Status: An Hypothesis-Generating Study. JCO 23: 7512-7517 [Abstract] [Full Text]  
• Banerjee, S., Smith, I. E., Folkerd, L., Iqbal, J., Barker, P., Dowsett, M., On behalf of the IMPACT trialists, (2005). Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial. Ann Oncol 16: 1632-1638 [Abstract] [Full Text]  
• Mann, B. S., Johnson, J. R., Kelly, R., Sridhara, R., Williams, G., Pazdur, R. (2005). Letrozole in the Extended Adjuvant Treatment of Postmenopausal Women with History of Early-Stage Breast Cancer Who Have Completed 5 Years of Adjuvant Tamoxifen. Clin. Cancer Res. 11: 5671-5677 [Abstract] [Full Text]  
• Shapiro, C. L. (2005). Aromatase Inhibitors and Bone Loss: Risks in Perspective. JCO 23: 4847-4849 [Full Text]  
• Boccardo, F., Rubagotti, A., Puntoni, M., Guglielmini, P., Amoroso, D., Fini, A., Paladini, G., Mesiti, M., Romeo, D., Rinaldini, M., Scali, S., Porpiglia, M., Benedetto, C., Restuccia, N., Buzzi, F., Franchi, R., Massidda, B., Distante, V., Amadori, D., Sismondi, P. (2005). Switching to Anastrozole Versus Continued Tamoxifen Treatment of Early Breast Cancer: Preliminary Results of the Italian Tamoxifen Anastrozole Trial. JCO 23: 5138-5147 [Abstract] [Full Text]  
• Boulay, A., Rudloff, J., Ye, J., Zumstein-Mecker, S., O'Reilly, T., Evans, D. B., Chen, S., Lane, H. A. (2005). Dual Inhibition of mTOR and Estrogen Receptor Signaling In vitro Induces Cell Death in Models of Breast Cancer. Clin. Cancer Res. 11: 5319-5328 [Abstract] [Full Text]  
• Oktay, K., Buyuk, E., Libertella, N., Akar, M., Rosenwaks, Z. (2005). Fertility Preservation in Breast Cancer Patients: A Prospective Controlled Comparison of Ovarian Stimulation With Tamoxifen and Letrozole for Embryo Cryopreservation. JCO 23: 4347-4353 [Abstract] [Full Text]  
• Yamaguchi, Y., Takei, H., Suemasu, K., Kobayashi, Y., Kurosumi, M., Harada, N., Hayashi, S.-i. (2005). Tumor-Stromal Interaction through the Estrogen-Signaling Pathway in Human Breast Cancer. Cancer Res. 65: 4653-4662 [Abstract] [Full Text]  
• Manquez, M E, Shields, C L, Karatza, E C, Shields, J A (2005). Regression of choroidal metastases from breast carcinoma using aromatase inhibitors. Br. J. Ophthalmol. 89: 776-777 [Full Text]  
• Thompson, L. U., Chen, J. M., Li, T., Strasser-Weippl, K., Goss, P. E. (2005). Dietary Flaxseed Alters Tumor Biological Markers in Postmenopausal Breast Cancer. Clin. Cancer Res. 11: 3828-3835 [Abstract] [Full Text]  
• Kudachadkar, R., O'Regan, R. M. (2005). Aromatase Inhibitors as Adjuvant Therapy for Postmenopausal Patients With Early Stage Breast Cancer. CA Cancer J Clin 55: 145-163 [Abstract] [Full Text]  
• Dowsett, M., Ebbs, S. R., Dixon, J. M., Skene, A., Griffith, C., Boeddinghaus, I., Salter, J., Detre, S., Hills, M., Ashley, S., Francis, S., Walsh, G., Smith, I. E. (2005). Biomarker Changes During Neoadjuvant Anastrozole, Tamoxifen, or the Combination: Influence of Hormonal Status and HER-2 in Breast Cancer--A Study from the IMPACT Trialists. JCO 23: 2477-2492 [Abstract] [Full Text]  
• Muller-Decker, K., Berger, I., Ackermann, K., Ehemann, V., Zoubova, S., Aulmann, S., Pyerin, W., Furstenberger, G. (2005). Cystic Duct Dilatations and Proliferative Epithelial Lesions in Mouse Mammary Glands upon Keratin 5 Promoter-Driven Overexpression of Cyclooxygenase-2. Am. J. Pathol. 166: 575-584 [Abstract] [Full Text]  
• Johnston, S. R. (2005). Combinations of Endocrine and Biological Agents: Present Status of Therapeutic and Presurgical Investigations. Clin. Cancer Res. 11: 889s-899s [Abstract] [Full Text]  
• Dunn, B. K., Wickerham, D. L., Ford, L. G. (2005). Prevention of Hormone-Related Cancers: Breast Cancer. JCO 23: 357-367 [Abstract] [Full Text]  
• Angelopoulos, N, Barbounis, V, Livadas, S, Kaltsas, D, Tolis, G (2004). Effects of estrogen deprivation due to breast cancer treatment. Endocr Relat Cancer 11: 523-535 [Abstract] [Full Text]  
• Gaddy, V. T., Barrett, J. T., Delk, J. N., Kallab, A. M., Porter, A. G., Schoenlein, P. V. (2004). Mifepristone Induces Growth Arrest, Caspase Activation, and Apoptosis of Estrogen Receptor-Expressing, Antiestrogen-Resistant Breast Cancer Cells. Clin. Cancer Res. 10: 5215-5225 [Abstract] [Full Text]  
• ESHRE Capri Workshop Group, (2004). Hormones and breast cancer. Hum Reprod Update 10: 281-293 [Abstract] [Full Text]  
• Oktay, K., Sonmezer, M. (2004). Ovarian tissue banking for cancer patients: Fertility preservation, not just ovarian cryopreservation. Hum Reprod 19: 477-480 [Abstract] [Full Text]  
• Goss, P. E., Strasser-Weippl, K. (2004). Prevention Strategies with Aromatase Inhibitors. Clin. Cancer Res. 10: 372S-379S [Abstract] [Full Text]  
• Burstein, H. J. (2003). Beyond Tamoxifen -- Extending Endocrine Treatment for Early-Stage Breast Cancer. NEJM 349: 1857-1859 [Full Text]  
• Stewart, P. M (2003). Improving clinical research. BMJ 327: 999-1000 [Full Text]  
• Forrest, A. R.W. (2003). Aromatase Inhibitors in Breast Cancer. NEJM 349: 1090-1090 [Full Text]