Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2009 Oct 7;2009(4):CD003370.
doi: 10.1002/14651858.CD003370.pub3.

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women

Lorna Gibson  1 , David Lawrence, Claire Dawson, Judith Bliss
Affiliations
Meta-Analysis

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women

Lorna Gibson et al. Cochrane Database Syst Rev. .

Abstract

Background: Endocrine therapy removes the influence of oestrogen on breast cancer cells and so hormonal treatments such as tamoxifen, megestrol acetate and medroxyprogesterone acetate have been in use for many years for advanced breast cancer. Aromatase inhibitors (AIs) inhibit oestrogen synthesis in the peripheral tissues and have a similar tumour-regressing effect to other endocrine treatments. Aminoglutethimide was the first AI in clinical use and now the third generation AIs, anastrozole, exemestane and letrozole, are in current use. Randomised trial evidence on response rates and side effects of these drugs is still limited.

Objectives: To compare AIs to other endocrine therapy in the treatment of advanced breast cancer in postmenopausal women.

Search strategy: For this update, the Cochrane Breast Cancer Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) and relevant conference proceedings were searched (to 30 June 2008).

Selection criteria: Randomised controlled trials in postmenopausal women comparing the effects of any AI versus other endocrine therapy, no endocrine therapy, or a different AI in the treatment of advanced (metastatic) breast cancer. Non-English language publications, comparisons of the same AI at different doses, AIs used as neoadjuvant treatment, or outcomes not related to tumour response were excluded.

Data collection and analysis: Data from published trials were extracted independently by two review authors and cross-checked by a third. Hazard ratios (HR) were derived for analysis of time-to-event outcomes (overall and progression-free survival). Odds ratios (OR) were derived for objective response, clinical benefit, and toxicity.

Main results: Thirty-seven trials were identified, 31 of which were included in the main analysis of any AI versus any other treatment (11,403 women). No trials were excluded due to inadequate allocation concealment. The pooled estimate showed a significant survival benefit for treatment with an AI over other endocrine therapies (HR 0.90, 95% CI 0.84 to 0.97). A subgroup analysis of the three commonly prescribed AIs (anastrozole, exemestane, letrozole) also showed a similar survival benefit (HR 0.88, 95% CI 0.80 to 0.96). There were very limited data to compare one AI with a different AI, but these suggested an advantage for letrozole over anastrozole.AIs have a different toxicity profile to other endocrine therapies. For those currently prescribed, and for all AIs combined, they had similar levels of hot flushes and arthralgia; increased risks of rash, nausea, diarrhoea and vomiting; but a 71% decreased risk of vaginal bleeding and 47% decrease in thromboembolic events compared with other endocrine therapies.

Authors' conclusions: In women with advanced (metastatic) breast cancer, aromatase inhibitors including those in current clinical use show a survival benefit when compared to other endocrine therapy.

PubMed Disclaimer

Conflict of interest statement

One of the authors (JMB) is a member of the management group and grant holder for the Intergroup Exemestane Study. This is funded by Pfizer, the producers of the aromatase inhibitor exemestane.

Figures

1.1
1.1. Analysis
Comparison 1: AI versus non‐AI, Outcome 1: Overall survival (reported or calculated)
1.2
1.2. Analysis
Comparison 1: AI versus non‐AI, Outcome 2: Progression‐free survival (reported or calculated)
1.3
1.3. Analysis
Comparison 1: AI versus non‐AI, Outcome 3: Clinical benefit (assessable)
1.4
1.4. Analysis
Comparison 1: AI versus non‐AI, Outcome 4: Objective response (assessable)
1.5
1.5. Analysis
Comparison 1: AI versus non‐AI, Outcome 5: Clinical benefit (randomised)
1.6
1.6. Analysis
Comparison 1: AI versus non‐AI, Outcome 6: Objective response (randomised)
2.1
2.1. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 1: hot flushes
2.2
2.2. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 2: nausea
2.3
2.3. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 3: vomiting
2.4
2.4. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 4: diarrhoea
2.5
2.5. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 5: rash
2.6
2.6. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 6: vaginal bleeding
2.7
2.7. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 7: thromboembolic
2.8
2.8. Analysis
Comparison 2: AI versus non‐AI: Toxicity, Outcome 8: arthralgia
3.1
3.1. Analysis
Comparison 3: Current AIs versus non‐AI, Outcome 1: Overall survival (reported or calculated)
3.2
3.2. Analysis
Comparison 3: Current AIs versus non‐AI, Outcome 2: Progression‐free survival (reported or calculated)
3.3
3.3. Analysis
Comparison 3: Current AIs versus non‐AI, Outcome 3: Clinical benefit (assessable)
3.4
3.4. Analysis
Comparison 3: Current AIs versus non‐AI, Outcome 4: Objective response (assessable)
3.5
3.5. Analysis
Comparison 3: Current AIs versus non‐AI, Outcome 5: Clinical benefit (randomised)
3.6
3.6. Analysis
Comparison 3: Current AIs versus non‐AI, Outcome 6: Objective response (randomised)
4.1
4.1. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 1: hot flushes
4.2
4.2. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 2: nausea
4.3
4.3. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 3: vomiting
4.4
4.4. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 4: diarrhoea
4.5
4.5. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 5: rash
4.6
4.6. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 6: vaginal bleeding
4.7
4.7. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 7: thromboembolic
4.8
4.8. Analysis
Comparison 4: Current AIs versus non‐AI: Toxicity, Outcome 8: arthralgia
5.1
5.1. Analysis
Comparison 5: AI versus different AI, Outcome 1: Overall survival (reported)
5.2
5.2. Analysis
Comparison 5: AI versus different AI, Outcome 2: Progession‐free survival (reported or calculated)
5.3
5.3. Analysis
Comparison 5: AI versus different AI, Outcome 3: Clinical benefit (assessable)
5.4
5.4. Analysis
Comparison 5: AI versus different AI, Outcome 4: Objective response (assessable)
5.5
5.5. Analysis
Comparison 5: AI versus different AI, Outcome 5: Clinical benefit (randomised)
5.6
5.6. Analysis
Comparison 5: AI versus different AI, Outcome 6: Objective response (randomised)
6.1
6.1. Analysis
Comparison 6: AI as first‐line therapy versus any other therapy (tamoxifen), Outcome 1: Overall survival (reported or calculated)
6.2
6.2. Analysis
Comparison 6: AI as first‐line therapy versus any other therapy (tamoxifen), Outcome 2: Progression‐free survival (reported or calculated)
6.3
6.3. Analysis
Comparison 6: AI as first‐line therapy versus any other therapy (tamoxifen), Outcome 3: Clinical benefit (assessable)
6.4
6.4. Analysis
Comparison 6: AI as first‐line therapy versus any other therapy (tamoxifen), Outcome 4: Objective response (assessable)
6.5
6.5. Analysis
Comparison 6: AI as first‐line therapy versus any other therapy (tamoxifen), Outcome 5: Clinical benefit (randomised)
6.6
6.6. Analysis
Comparison 6: AI as first‐line therapy versus any other therapy (tamoxifen), Outcome 6: Objective response (randomised)
7.1
7.1. Analysis
Comparison 7: AI as second‐line therapy versus any other therapy, Outcome 1: Overall survival (reported or calculated)
7.2
7.2. Analysis
Comparison 7: AI as second‐line therapy versus any other therapy, Outcome 2: Progression‐free survival (reported or calculated)
7.3
7.3. Analysis
Comparison 7: AI as second‐line therapy versus any other therapy, Outcome 3: Clinical benefit (assessable)
7.4
7.4. Analysis
Comparison 7: AI as second‐line therapy versus any other therapy, Outcome 4: Objective response (assessable)
7.5
7.5. Analysis
Comparison 7: AI as second‐line therapy versus any other therapy, Outcome 5: Clinical benefit (randomised)
7.6
7.6. Analysis
Comparison 7: AI as second‐line therapy versus any other therapy, Outcome 6: Objective response (randomised)
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Alonso‐Munoz 1988 {published data only}
    1. Alonso-Munzo MC, Ojeda-Gonzalez M, Beltran-Fabregat M, Dorca-Ribugent J, Lopez-Lopez L, Borras-Balada J et al. Randomized trial of tamoxifen versus aminoglutethimide and versus combined tamoxifen and aminoglutethimide in advanced postmenopausal breast cancer. Oncology 1988;45:350-3. - PubMed
Bezwoda 1998 {published data only}
    1. Bezwoda WR, Gudgeon A, Falkson G, Jordaan JP, Goedhals L. Fadrozole versus megestrol acetate: a double-blind randomised trial in advanced breast cancer. Oncology 1998;55:416-20. - PubMed
Bonneterre 2001 {published data only}
    1. Bonneterre J, Buzdar A, Nabholtz JA, Robertson JFR, Thuerlimann B, von Euler M et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001;92(9):2247-58. - PubMed
    1. Bonneterre J, Thuerlimann B, Robertson JFR, Krzakowski M, Mauriac L, Koralewski P, et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the tamoxifen or arimidex randomized group efficacy and tolerability study. Journal of Clinical Oncology 2000;18(22):3748-57. - PubMed
    1. Nabholtz JM, Bonneterre J, Buzdar A, Robertson JFR, Thuerlimann B. Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. European Journal of Cancer 2003;39:1684-9. - PubMed
    1. Nabholtz JM, Buzdar A, Pollak M, Harwin W, Burton G, Mangalik A 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. Journal of Clinical Oncology 2000;18(22):3758-67. - PubMed
    1. Nabholtz JM. Advanced breast cancer updates on anastrozole versus tamoxifen. Journal of Steroid Biochemistry and Molecular Biology 2003;86:321-5. - PubMed
Buzdar 1996a {published data only}
    1. Budzar A, Jonat W, Howell A, Jones SE, Blomqvist C, Vogel CL et al. Anastrozole, a potent and selective aromatase inhibitor, versus megestrol acetate in postmenopausal women with advanced breast cancer: results of overview analysis of two phase III trials. Journal of Clinical Oncology 1996;14:2000-11. - PubMed
    1. Buzdar AU, Jonat W, Howell A, Jones SE, Blomqvist CP, Vogel CL et al. Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma. Cancer 1998;83(6):1142-52. - PubMed
    1. Buzdar AU, Jonat W, Howell A, Plourde PV. Arimidex: a potent and selective aromatase inhibitor for the treatment of advanced breast cancer. Journal Steroid Biochemistry Molecular Biology 1997;61(3-6):145-9. - PubMed
    1. Drummond M, Thompton E, Howell A, Jonat W, Buzdar A, Brown J. Cost-effectiveness implications of increased survival with anastrozole in the treatment of advanced breast cancer. Journal of Medical Economics 1999;2:33-43.
    1. Jonat W, Howell A, Blomqvist C, Eiermann W, Winblad G, TyrrellC et al. A randomized trial comparing two doses of the new selective aromatase inhibitor anastrozole (Arimidex) with megestrol acetate in postmenopausal women with advanced breast cancer. European Journal of Cancer 1996;32A(3):404-12. - PubMed
Buzdar 1996b {published data only}
    1. Buzdar A, Smith R, Vogel C, Bonomi P, Keller AM, Favis G et al. Fadrazole HCl (CGS-16949A) versus megestrol acetate in postmenopausal patients with metastatic breast carcinoma: results of two randomized, double-blind, controlled multi-institutional trials. Cancer 1996;77(12):2503-13. - PubMed
Buzdar 1996c {published data only}
    1. Buzdar A, Smith R, Vogel C, Bonomi P, Keller AM, Favis G et al. Fadrazole HCl (CGS-16949A) versus megestrol acetate in postmenopausal patients with metastatic breast carcinoma: results of two randomized, double-blind, controlled multi-institutional trials. Cancer 1996;77(12):2503-13. - PubMed
Buzdar 2001 {published data only}
    1. Buzdar A, Douma J, Davidson N, Elledge R, Morgan M, Smith R et al. Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol acetate. Journal of Clinical Oncology 2001;19(14):3357-66. - PubMed
Canney 1988 {published data only}
    1. Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, Spooner D. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. Journal of the National Cancer Institute 1988;80(14):1147-51. - PubMed
Chia 2008 {published data only}
    1. Chia S, Gradishar W, Mauriac L, Bines J, Amant F, Federico M et al. Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior nonsteroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. Journal of Clinical Oncology 2008;26(10):1664-70. - PubMed
Dombernowsky 1998 {published data only}
    1. Dombernowsky P, Smith I, Falkson G, Leonard R, Panasci L, Bellmunt J 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 acetate. Journal of Clinical Oncology 1998;16(2):453-61. - PubMed
Falkson 1996 {published data only}
    1. Falkson CI, Falkson HC. A randomised study of CGS 16949A (fadrozole) versus tamoxifen in previously untreated postmenopausal patients with metastatic breast cancer. Annals of Oncology 1996;7:465-9. - PubMed
Freue 2000 {published data only}
    1. Freue M, Kjaer C, Boni J, Joliver F, Jaenicke F, Willemse PhHB et al. Open comparative trial of formestane versus megestrol acetate in postmenopausal patients with advanced breast cancer previously treated with tamoxifen. The Breast 2000;9:9-16. - PubMed
Gale 1994 {published data only}
    1. Gale KE, Andersen JW, Tormey DC, Mansour EG, David TE, Horton J et al. Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen. Cancer 1994;73(2):354-361. - PubMed
Garcia‐Giralt 1992 {published data only}
    1. Garcia-Giralt E, Ayme Y, Carton M, Daban A, Delozier T, Fargeot P et al. Second and third line hormonotherapy in advanced post-menopausal breast cancer: a multicenter randomized trial comparing medroxyprogesterone acetate with aminoglutethimide in patients who have become resistant to tamoxifen. Breast Cancer Research and Treatment 1992;24:139-45. - PubMed
Gershanovich 1998 {published data only}
    1. Gershanovich M, Chaudri HA, Campos D, Lurie H, Bonaventura A, Jeffrey M et al. Letrozole, a new oral aromatase inhibitor: randomised trial comparing 2.5mg daily, 0.5 mg daily and aminoglutethimide in postmenopausal women with advanced breast cancer. Annals of Oncology 1998;9:639-45. - PubMed
    1. Gershanovitch M. Letrozole, a new aromatase for advanced breast cancer. Voprosy Onkolgii 45;4:361-8. - PubMed
Goss 1999 {published data only}
    1. Goss PE, Winer EP, Tannock IF, Schwarz LH. Randomized phase III trial comparing the new potent and selective third generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients. Journal of Clinical Oncology 1999;17(1):52-63. - PubMed
Goss 2007 {published data only}
    1. Goss P, Bondarenko IN, Mankhas GN, Pendergrass KB, Miller WH, Langecker P et al. Phase III, double-blind, controlled trial of atamastane plus toremifene compared with letrozole in postmenopausal women with advanced receptor-positive breast cancer. Journal of Clinical Oncology 2007;25(31):4961-6. - PubMed
Ingle 1986 {published data only}
    1. Ingle JN, Green SJ, Ahmann DL, Long HJ, Edmonson JH, Rubbin J et al. Randomized trial of tamoxifen alone or combined with aminoglutethimide and hydrocortisone in women with metastatic breast cancer. Journal of Clinical Oncology 1986;4(6):958-64. - PubMed
Kaufmann 2000 {published data only}
    1. Hillner BE, Radice D. Cost-effectiveness analysis of exemestane compared with megestrol in patients with advanced breast carcinoma. Cancer 2001;91(3):484-9. - PubMed
    1. Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Cervek J et al. Exemestane improves survival compared with megestrol acetate in postmenopausal patients with advanced breast cancer who have failed on tamoxifen: results of a double-blind randomised phase III trial. European Journal of Cancer 2000;36 Suppl:81-91. - PubMed
    1. Kaufmann M, Bajetta E, Dirix LY, Fein LE, Jones SE, Zilembo N et al. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomised double-blind trial. Journal of Clinical Oncology 2000;18(7):1399-411. - PubMed
Kleeberg 1997 {published data only}
    1. Kleeberg UR, Dowsett M, Carrion RP, Dodwell DJ, Vorobiof DA, Aparicio LA, Robertson JFR. A randomised comparison of oestrogen suppression with anastrozole and formestane in postmenopausal patients with advanced breast cancer. Oncology 1997;54 Suppl 2:19-22. - PubMed
    1. Vorobiof DA, Kleeberg UR, Perez-Carrion R, Dodwell DJ, Robertson JFR, Calvo L et al. A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex) with intramuscular formestane in postmenopausal women with advanced breast cancer. Annals of Oncology 1999;10:1219-25. - PubMed
Leitzel 1995 {published data only}
    1. Leitzel K, Teramoto Y, Konrad K, Chinchilli VM, Volas G, Grossberg H et al. Elevated Serum c-erb B-2 Antigen levels and decreased response to hormone therapy of breast cancer. Journal of Clinical Oncology 1995;13(5):1129-35. - PubMed
Lundgren 1989 {published data only}
    1. Lundgren S, Gundersen S, Klepp R, Lonning PE, Lund E, Kvinnsland S. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Research and Treatment 1989;14:201-6. - PubMed
Mauriac 2003 {published data only}
    1. Howell A, Robertson JFR, Quaresma Albano J, Ascgermannova A, Mauriac L, Kleeberg UR et al. Fulvestrant, formerly ICI 182, 780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. Journal of Clinical Oncology 2002;20(16):3396-403. - PubMed
    1. Mauriac L, Pippen JE, Quaresma Albano J, Gertler SZ Osborne CK. Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metasteses: combined results from two multicentre trials. European Journal of Cancer 2003;39(9):1228-33. - PubMed
    1. Osborne CK, Pippen J, Jones, SE, Parker LM, Ellis M, Come S et al. Double-blind, randomized trial comparing the efficacy and tolerability of the fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American Trial. Journal of Clinical Oncology 2002;20(16):3386-95. - PubMed
    1. Robertson JFR, Osborne CK, Howell A, Jones SE, Mauriac L, Ellis M et al. Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women. Cancer 2003;98(2):229-38. - PubMed
    1. Vergote I. Fulvestrant versus anastrozole as second-line treatment of advanced breast cancer in postmenopausal women. European Journal of Cancer 2002;38 Suppl(6):57-8. - PubMed
Mercer 1993 {published data only}
    1. Mercer PM, Ebbs SR, Fraser SCA, Coltart RS, Bates T. Trial of aminoglutethimide vs hydrocortisone as second-line hormone treatment of advanced breast cancer. European Journal of Surgical Oncology 1993;19:254-8. - PubMed
Milla‐Santos 2003 {published data only}
    1. Milla-Santos A, Milla L, Portella J, Rallo L, Pons M, Rodes E et al. Anastrozole versus tamoxifen as first-line therapy in postmenopausal patients with hormone-dependent advanced breast cancer. American Journal of Clinical Oncology 2003;26(3):317-22. - PubMed
Mourisden 2001 {published data only}
    1. Irish W, Sherrill B, Cole B, Gard C, Glendenning GA, Mourisden H. Quality-adjusted survival in a crossover trial of letrozole versus tamoxifen in postmenopausal women with advance breast cancer. Annals of Oncology 2005;16:1458-62. - PubMed
    1. Lipton A, Ali SM, Leitzel K, Demers L, Harvey HA, Chaudri-Ross HA et al. Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen. Journal of Clinical Oncology 2003;21(10):1967-72. - PubMed
    1. Mourisden H, Chaudri-Ross HA. Efficacy of First-Line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer. The Oncologist 2004;9:497-506. - PubMed
    1. Mourisden H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A 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. Journal of Clinical Oncology 2003;21(11):2101-9. - PubMed
    1. Mourisden H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A et al. Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced brreast cancer: results of a phase III study of the international letrozole breast cancer group. Journal of Clinical Oncology 2001;19(10):2596-606. - PubMed
Paridaens 2003 {published data only}
    1. Atalay G, Dirix L, Biganzoli L, Beex L, Nooji M, Cameron D et al. The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a comparison 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'. Annals of Oncology 2004;15(2):211-7. - PubMed
    1. Paridaens R, Dirix L, Lohrisch C, Beex L, Nooji M, Cameron D et al. Mature results of a randomized phase II multicenter study of exemextane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer. Annals of Oncology 2003;14:1391-8. - PubMed
Perez Carrion 1994 {published data only}
    1. Perez Carrion R, Alberola Candel V, Calabresi F, Michel RT, Santos R, Delozier T et al. Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line therapy in postmenopausal women with advanced breast cancer. Annals of Oncology 1994;5 Suppl 7:19-24. - PubMed
Powles 1984 {published data only}
    1. Powles TJ, Ashley S, Ford HT, Gazet JC, Nash AG, Neville AM, Coombes RC. Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially. The Lancet 1984;1(8391):1369-72. - PubMed
Rose 1986 {published data only}
    1. Rose C, Kamby C, Mouridsen HT, Andersson M, Bastholt L, Moller KA et al. Combined endocrine treatment of elderly postmenopausal patients with metastatic breast cancer. Breast Cancer Research and Treatment 2000;61(2):103-10. - PubMed
    1. Rose C, Kamby C, Mouridsen HT, Bastholt L, Brincker H, Skovaard-Poulsen H et al. Combined endocrine treatment of postmenopausal patients with advanced breast cancer. A randomised trial of tamoxifen vs. tamoxifen plus aminoglutethimide and hydrocortisone. Breast Cancer Research and Treatment 1986;7 Suppl:45-50. - PubMed
Rose 2003 {published data only}
    1. Rose C, Vtoraya O, Pluzanska A, Davidson N, Gershanovich M, Thomas R et al. An open randomised trial of second-line endocrine therapy in advanced breast cancer. European Journal of Cancer 2003;39(16):2318-27. - PubMed
    1. Tobias JS, Howell A. An open randomised trial of second-line endocrine therapy in advanced breast cancer: comparison of the aromatase inhibitors letrozole and anastrozole. European Journal of Cancer 2004;40(12):1913. - PubMed
Russell 1997 {published data only}
    1. Russell C, Green SJ, O'Sullivan J, Hynes HE, Budd T, Congdon JE et al. Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a southwest oncology group phase III trial. Journal of Clinical Oncology 1997;15(7):2494-501. - PubMed
Samonis 1994 {published data only}
    1. Samonis G, Margioris AN, Bafaloukos D, Razis DV. Prospective randomized study of aminoglutethimide (AG) versus medroxyprogesterone acetate (MPA) versus AG+MPA in generalized breast cancer. Oncology 1994;51(5):411-5. - PubMed
Schmid 2001 {published data only}
    1. Schmid P, Wischnewsky MB, Possinger K. Self organizing maps and prognosis of advanced breast cancer patients with bone metastases receiving letrozole or MA. Breast Cancer Research and Treament 2001;64:77.
Thuerlimann 1996 {published data only}
    1. Thuerlimann B, Beretta K, Bacchi M, Castiglione-Gertsch M, Goldhirsch A, Jungi WF et al. First-line fadrozole HCI (CGS 16949A) versus tamoxifen in postmenopausal women with advanced breast cancer. Annals of Oncology 1996;7:471-9. - PubMed
Thuerlimann 1997 {published data only}
    1. Bernhard J, Casiglione-Gertsch M, Hsu Schmitz S-F, Thuerlimann B, Cavalli F, Morant R et al. Quality of life in postmenopausal patients with breast cancer after failure of tamoxifen: formestane versus megestrol acetate as second-line hormonal treatment. European Journal of Cancer 1999;35(6):913-20. - PubMed
    1. Bernhard J, Thuerlimann B, Hsu Schmitz S-F, Castiglione-Gertsch M, Cavalli F, Morant R et al. Defining clinical benefit in postmenopausal patients with breast cancer under second-line endocrine treatment: does quality of life matter. Journal of Clinical Oncology 1999;17(6):1672-9. - PubMed
    1. Thuerlimann B, Castiglione M, Hsu-Scmitz SF, Cavalli F, Bonnefoi H, Fey MF et al. Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). European Journal of Cancer 1997;33(7):1017-24. - PubMed
Tominaga 2003 {published data only}
    1. Tominaga T, Adachi I, Sasaki Y, Tabei T, Ikeda T, Takatsuka Y et al. Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer. Annals of Oncology 2003;14:62-70. - PubMed

References to studies excluded from this review

Abe 2002 {published data only}
    1. Abe R, Tominaga T, Nomizu T, Nomura Y, Takashima S, Koyama H et al. CGS20267 (letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no. 1) - investigation of recommended clinical dose CGS20267 Study Group. Gan To Kaguku Ryoho 2002;29(5):729-40. - PubMed
Bajetta 1994 {published data only}
    1. Bajetta E, Zilembo N, Buzzoni R, Noberasco C, Di Leo A, Bartoli C et al. Endocrinological and clinical evaluation of two doses of formestane in advanced breast cancer. British Journal of Cancer 1994;70:145-50. - PMC - PubMed
    1. Ferrari L, Zilembo N, Bajetta, Buzzoni R, Noberasco C, Martinetti A et al. Effect of two 4-hydroxyandrostenedione doses on serum insulin-like growth factor I levels in advanced breast cancer. Breast Cancer Research and Treatment 1994;30:127-32. - PubMed
Bajetta 1997 {published data only}
    1. Bajetta E, Zilembo N, Noberasco C, Martinetti A, Mariani L, Ferrari L et al. The minimal effective exemestane dose for endocrine activity in advanced breast cancer. European Journal of Cancer 1997;33(4):587-91. - PubMed
Bajetta 1997a {published data only}
    1. Bajetta E, Ferrari L, Celio L, Mariana L, Miceli R, Di Leo A et al. The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. Journal of Steroid Biochemistry 1997;63(4-6):261-7. - PubMed
Bajetta 1999 {published data only}
    1. Bajetta E, Zilembo N, Dowsett M, Guillevin L, Di Leo A, Celio L et al. Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses in postmenopausal breast cancer patients. European Journal of Cancer 1999;35(2):208-13. - PubMed
Beretta 1990 {published data only}
    1. Beretta KR, Hoeffken K, Kvinnsland S, Trunet P, Chaudri HA, Bhatnagar AS et al. CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer - a phase I study. Annals of Oncology 1990;1(6):421-6. - PubMed
Bruning 1989 {published data only}
    1. Bruning PF, Bonfer JMG, Hart AAM, Linden E, Jong-Bakker M, Moolenaar AJ, Nooijen WJ. Low dose aminoglutethimide without hydrocortisone for the treatment of advanced postmenopausal breast cancer. European Journal of Clinical Oncology 1989;25(2):369-76. - PubMed
Bruning 1990 {published data only}
    1. Bruning PF, Bonfrer JMG, Wildiers J, Jassem J, Beex LVAM, Schorangel J, Nooijen WJ. Second-line endocrine treatment of postmenopausal advanced breast cancer preliminary endocrine results of a 5-arm randomized phase II trial of medium vs low dose aminoglutethimide, with or without hydrocortisone vs hydrocortisone alone (EORTC 10861). Journal of Steroid Biochemistry 1990;37(6):1013-9. - PubMed
Castelazo 2004 {published data only}
    1. Castelazo RG, Molotia Xolalpa D, Basavilvazo Rodriguez MA, Angeles Victoria L, Zarate A, Hernandez-Valencia M. Survival of breast cancer patients treated with inhibitors of the aromatase vs tamoxifen. Ginecologia y Obstetricia de Mexico 2004;72:493-9. - PubMed
Cataliotti 2006 {published data only}
    1. Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K. Comparison of anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer. Cancer 2006;106(10):2095-103. - PubMed
Dixon 2000 {published data only}
    1. Dixon JM, Renshaw L, Bellamy C, Stuart M, Hoctin-Boes G, Miller WR. The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: a randomized, double-blind, single-center study. Clinical Cancer Research 2000;6(6):2229-35. - PubMed
Dowsett 1989 {published data only}
    1. Dowsett M, Cunningham DC, Stein RC, Evans S, Dehennin L, Hedley A, Coombes RC. Dose-related endocrine effects and pharmokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Research 1989;49:1306-12. - PubMed
Dowsett 1990 {published data only}
    1. Dowsett M, Stein RC, Mehta A, Coombes RC. Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients. Clinical Endocrinology 1990;32:623-34. - PubMed
Dowsett 1994 {published data only}
    1. Bonnefoi HR, Smith IE, Dowsett M, Trunet, Houston SJ, da Luz RJ et al. Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer. British Journal of Cancer 1996;73:539-42. - PMC - PubMed
    1. Dowsett M, Smithers D, Moore J, Trunet PF, Coombes RC, Powles TJ et al. Endocrine changes with the aromatase inhibitor fadrozole hydrochloride in breast cancer. European Journal of Cancer 1994;30A(10):1453-8. - PubMed
Dowsett 1995 {published data only}
    1. Dowsett M, Jones A, Johnston SRD, Jacobs S, Trunet P, Smith IE. In vivo measturement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clinical Cancer Research 1995;1:1511-5. - PubMed
Eiermann 2001 {published data only}
    1. Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter study. Annals of Oncology 2001;12:1527-32. - PubMed
Geisler 1996 {published data only}
    1. Geisler J, King N, Dowsett M, Ottestad L, Lundgren S, Walton P et al. Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in post menopausal women with breast cancer. British Journal of Cancer 1996;74:1286-91. - PMC - PubMed
Geisler 2002 {published data only}
    1. Geisler J, Haynes B, Anker G, Dowsett M, Loenning PE. Influence of letrozole and anastrozole on totla body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomised, cross-over study. Journal of Clinical Oncology 2002;20(3):751-7. - PubMed
Ingle 1997 {published data only}
    1. Ingle JN, Johnson PA, Suman VJ, Gerstner JB, Mailliard JA, Camoriano JK et al. A randomized phase II trial of two dosage levels of letrozole as third-line hormonal therapay for women with metastatic breast carcinoma. Cancer 1997;80:218-24. - PubMed
Johnston 1994 {published data only}
    1. Johnston SRD, Smith IE, Doody D, Jacobs S, Robertshaw H, Dowsett M. Clinical and endocrine effects of the oral aromatase inhibitor vorozole in postmenopausal patients with advanced breast cancer. Cancer Research 1994;54:5875-81. - PubMed
Miller 1996b {published data only}
    1. Miller AA, Lipton A, Henderson IC, Navari R, Mulagha MT, Cooper J. Fadrozole hydrochloride in postmenopausal patients with metastatic breast carcinoma. Cancer 1996;78:789-93. - PubMed
Pronzato 1993 {published data only}
    1. Pronzato P, Rubagotti A, Amoroso D, Bertelli G, Queirolo P, Sertoli MR, Rosso M et al. Second-line hormone therapy for breast cancer. Uselessness of first-line continuation. American Journal of Clinical Oncology 1993;16(6):522-5. - PubMed
Raats 1992 {published data only}
    1. Falkson G, Raats JI, Falkson H. Fadrozole hydrochloride, a new nontoxic aromatase inhibitor for the treatment of patients with metastatic breast cancer. Journal of Steroid and Biochemistry and Molecular Biology 1992;43(1-3):161-5. - PubMed
    1. Raats JI, Falkson G, Falkson H. A study of fadrozole, a new aromatase inhibitor, in postmenopasual women with advanced metastatic breast cancer. Journal of Clinical Oncology 1992;10(1):111-6. - PubMed
Smith 2005 {published data only}
    1. Smith IE, Dowsett M, Ebbs SR, Dixon MJ, Skene A, Blohmer JU et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: the IMPACT multicenter double-blind randomized trial. Journal of Clinical Oncology 2005;23(22):5108-16. - PubMed
Svenstrup 1994 {published data only}
    1. Svenstrup B, Herrstedt J, Bruenner N, Bennet P, Wachmann H, Dombernowsky P. Sex hormone levels in postmenopausal women with advanced metastatic breast cancer treated with CGS 169 49A. European Journal of Cancer 1994;30A(9):1254-8. - PubMed
Wang 2003 {published data only}
    1. Wang HQ, Ren CC, Feng WJ, Lin MB, Xiong YQ, Huang P et al. Treatment of advanced metastatic breast cancer with exemestane, a multicenter randomized controlled study of 195 cases. Zhonghua Yi Xue Za Zhi 2003;83(3):188-90. - PubMed

References to ongoing studies

CAAN {published data only}
    1. CAAN. Ongoing study. February 2002. Contact author for more information.
ECOG E4101 {published data only}
    1. ECOG E4101. Ongoing study. Starting date of trial not provided. Contact author for more information.
ICR‐CTSU Sofea {published data only}
    1. SofeaPhase III. Ongoing study. March 2004. Contact author for more information.
Paridaens 2003 {published data only}
    1. Phase III EORTC-10951. Ongoing study. Starting date of trial not provided. Contact author for more information.

Additional references

Beatson 1896
    1. Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma. Suggestions for a new method of treatment with illustrative cases. Lancet 1896;2:104-7. - PMC - PubMed
EBCTCG 2005
    1. Early Breast Cancer Trialists' Cooperative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-1717. - PubMed
Ferlay 2000 [Computer program]
    1. Globocan 2000: Cancer Incidence, Mortality and Prevalence Worldwide. Ferlay J, Bray F, Pisani P and Parkin DM, Version 1. Lyon: IARC Press, 2001.
Gibson 2007
    1. Gibson LJ, Dawson CL, Lawrence DJ, Bliss JM. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858] - DOI - PubMed
Hayward 1977
    1. Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD. Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer 1977;39(3):1289-94. - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. - PMC - PubMed
Howell 1997
    1. Howell A, Dowsett M. Recent advances in endocrine therapy of breast cancer. BMJ 1997;315:863-6. - PMC - PubMed
Ibrahim 1995
    1. Ibrahim NK, Buzdar AU. Aromatase inhibitors: current status. American Journal of Clinical Oncology 1995;18(5):407-17. - PubMed
Mauri 2006
    1. Mauri D, Pavlidis N, Polyzos NP, Ioannidis JP. Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: meta-analysis. Journal of the National Cancer Institute 2006;98(18):1285-91. - PubMed
Miller 1996a
    1. Miller WR. Aromatase inhibitors. Endocrine-related Cancer 1996;3:65-79.
Parmar 1995
    1. Parmar MKB, Machin D. Survival analysis: A Practical Approach. John Wiley, 1995.
Roseman 1997
    1. Roseman BJ, Buzdar AU, Singletary SE. Use of aromatase inhibitors in postmenopausal women with advanced breast cancer. Journal of Surgical Oncology 1997;66:215-20. - PubMed

References to other published versions of this review

Cochrane 2007
    1. Gibson LJ, Dawson CK, Lawrence DH, Bliss JM. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database of Systematic Reviews 2007, Issue 1. - PubMed

MeSH terms

Substances