Susan G Komen  
I've Been Diagnosed With Breast Cancer Someone I Know Was Diagnosed Share Your Story Join Us And Stay Informed Donate To End Breast Cancer
Home > Understanding Breast Cancer > Breast Cancer Research > Table 43: Aromatase inhibitors and disease-free survival in early breast cancer

  


Table 43: Aromatase inhibitors and disease-free survival in early breast cancer

This summary table contains detailed information about research studies. Summary tables offer an informative look at the science behind many breast cancer guidelines and recommendations. However, they should be viewed with some caution. In order to read and interpret research tables successfully, it is important to understand some key concepts. Learn how to read a research table.

Introduction: Aromatase inhibitors lower estrogen levels in the body by blocking aromatase, an enzyme that converts other hormones into estrogen. Aromatase inhibitors are used to treat hormone-receptor positive breast cancers, either as a first hormone therapy or after treatment with tamoxifen. Aromatase inhibitors are only used to treat postmenopausal women.

Treatment with an aromatase inhibitor (alone or after tamoxifen) lowers the risk of [1]:

  • Breast cancer recurrence
  • Breast cancer in the opposite breast
  • Death from breast cancer

The aromatase inhibitors anastrozole (Arimidex), exemestane (Aromasin) and letrozole (Femara) all have a similar treatment benefit [1]. They also have similar side effects. However, a person may tolerate one drug better than another.  

Learn more about aromatase inhibitors.

Side effects of aromatase inhibitors versus tamoxifen

Aromatase inhibitors have some side effects. They can cause menopausal symptoms, a loss of bone mineral density, joint pain and muscle pain. Compared to tamoxifen, they are more likely to increase the risk of bone fractures and heart problems [2-6].

Learn more about the side effects of aromatase inhibitors.

Learn about the strengths and weaknesses of different types of studies.

Study selection criteria: Randomized clinical trials of aromatase inhibitors with at least 350 participants (all postmenopausal women with hormone receptor-positive early breast cancer) and meta-analyses.

Study 

Study Population (number of participants) 

Treatments Studied  

Follow-up (years) 

Disease-free Survival
(percent of women alive without breast cancer at end of follow-up)
 

 

Aromatase inhibitor 

Hormone therapy
with tamoxifen or placebo
 

Randomized clinical trials 

Tamoxifen for fewer than 29 days, then switch to aromatase inhibitor 

ATAC Trial [3]

5,216

Anastrozole
vs.
tamoxifen alone

10

72%

68%*

BIG 1-98 Collaborative Group [7]

4,922

Letrozole
vs.
tamoxifen alone

8

76%

72%*

Tamoxifen for 1-4 years, then switch to aromatase inhibitor 

IES Trial [8]

4,599

 Exemestane following tamoxifen vs. continued use of tamoxifen

8

82%

78%*

ABCSG-8 trial [9]

3,714

Anastrozole following tamoxifen vs. continued use of tamoxifen 

5

89%

86%

ARNO 95 trial [10]

979

Anastrozole following tamoxifen vs. continued use of tamoxifen

3

92%

89%* 

N-SAS BC03 study (Japan) [11]

696

Anastrozole following tamoxifen vs. continued use of tamoxifen 

4

94%

91%

Italian Tamoxifen Anastrozole Trial [12]

448

Anastrozole following tamoxifen vs. continued use of tamoxifen

11

80%

71%*

Tamoxifen for 5 years, then switch to aromatase inhibitor 

MA-17 Trial [13-15]

5,170

Letrozole
vs.
placebo

4

94%

91%*,† 

NSABP [16]   

1,562

Exemestane following tamoxifen vs. placebo

3

91%

89% 

Meta-analyses 

EBCTCG [1] 9,856 Aromatase inhibitor
vs.
tamoxifen
6 88% 85%
  9,015 Switch to aromatase inhibitor after
2-3 years of tamoxifen
4 92% 89%

* Statistically significant difference between the two groups. 

† When studied by race, results showed a survival benefit for Caucasian women, but not among women of other races. Many women switched from placebo to letrozole after the first study results showed a benefit with letrozole. These women were included in the disease-free survival rates for those who took placebo. More recent findings adjusted for the effects of the women randomized to placebo that switched to letrozole and also showed better five-year disease-free survival with letrozole compared to placebo. 

‡ Some women switched from placebo to exemestane after the first study results showed a benefit with exemestane. These women are included in the disease-free survival rates for those who took placebo. 
 

References  

  1. Dowsett M, Cuzick J, Ingle J, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 28(3):509-18, 2010. 
  2. Perez EA, Josse RG, Pritchard KI, et al. Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: A companion study to NCIC CTG MA.17. J Clin Oncol. 24(22):3629-35, 2006.
  3. Cuzick J, Sestak I, Baum M, et al. for the ATAC/LATTE investigators. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol. 11(12):1135-41, 2010.
  4. Lonning PE, Geisler J, Krag LE, 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. 23(22):5126-37, 2005.
  5. Rabaglio M, Sun Z, Price KN, et al. for the BIG 1-98 Collaborative and International Breast Cancer Study Groups. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol. 20(9):1489-98, 2009.
  6. Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 103(17):1299-309, 2011.
  7. Regan MM, Neven P, Giobbie-Hurder A, et al. for the members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group (IBCSG). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol. 12(12):1101-1108, 2011.
  8. Bliss JM, Kilburn LS, Coleman RE, et al. Disease-related outcomes with long-term follow-up: an updated analysis of the intergroup exemestane study. J Clin Oncol. 30(7):709-17, 2012.
  9. Dubsky PC, Jakesz R, Mlineritsch B, et al. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol. 30(7):722-8, 2012.
  10. Kaufmann 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. 25(19):2664-70, 2007.
  11. Aihara T, Takatsuka Y, Ohsumi S, et al. Phase III randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in Japanese postmenopausal women with hormone-responsive breast cancer: N-SAS BC03 study. Breast Cancer Res Treat. 121(2):379-87, 2010.
  12. Boccardo F, Guglielmini P, Bordonaro R, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: long term results of the Italian Tamoxifen Anastrozole trial. Eur J Cancer. 49(7):1546-54, 2013. 
  13. Ingle JN, Tu D, Pater JL, et al. Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17. Ann Oncol. 19(5):877-82, 2008.
  14. Moy B, Tu D, Pater JL, et al. Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Ann Oncol. 17(11):1637-43, 2006.
  15. Jin H, Tu D, Zhao N, Shepherd LE, Goss PE. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 30(7):718-21, 2012.
  16. Mamounas EP, Jeong JH, Wickerham DL, et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 trial. J Clin Oncol. 26(12):1965-71, 2008.

Updated 01/13/14