Research table: Aromatase inhibitors for early breast cancer treatment

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s 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. Postmenopausal women may take an aromatase inhibitor. Some premenopausal women may take an aromatase inhibitor when it’s combined with ovarian suppression.

For women with early breast cancer, treatment with an aromatase inhibitor (alone or after tamoxifen) lowers the risk of [1]:

• Breast cancer recurrence (a return of breast cancer)
• 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, including possible side effects.

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

Study selection criteria: Randomized clinical trials 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 and with no breast cancer recurrence at the 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 [2]	5,216	Anastrozole vs. tamoxifen alone	10	72%	68%*
BIG 1-98 Collaborative Group [3]	3,833	Letrozole vs. tamoxifen alone	13	63%	60%
Randomized clinical trials – Tamoxifen for 1-4 years, then switch to aromatase inhibitor
IES Trial [4]	4,599	Exemestane following tamoxifen vs. continued use of tamoxifen	10	72%	68%*
ABCSG-8 trial [5]	3,714	Anastrozole following tamoxifen vs. continued use of tamoxifen	5	89%	86%
ARNO 95 trial [6]	979	Anastrozole following tamoxifen vs. continued use of tamoxifen	3	92%	89%*
N-SAS BC03 study (Japan) [7]	696	Anastrozole following tamoxifen vs. continued use of tamoxifen	8	63%	56%
Italian Tamoxifen Anastrozole Trial [8]	448	Anastrozole following tamoxifen vs. continued use of tamoxifen	11	80%	71%*
Randomized clinical trials – Tamoxifen for 5 years, then switch to aromatase inhibitor
MA-17 Trial [9-11]	5,170	Letrozole following tamoxifen vs. placebo	4	94%	91%*,†
NSABP [12]	1,562	Exemestane following tamoxifen vs. placebo	3	91%	89%‡
Meta-analyses
EBCTCG [1]	9,885	Aromatase inhibitor vs. tamoxifen	10	81%	77%
	11,798	Switched to aromatase inhibitor after 2-3 years of tamoxifen	10	83%	81%

* Statistically significant difference between the 2 groups.

† Many women switched from placebo to letrozole after early study results showed a benefit with letrozole. These women were included in the disease-free survival rates for those who took a placebo.

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

References

1. Dowsett M, Forbes JF, Bradley R, et al. for the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 386(10001):1341-52, 2015.
2. 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.
3. Ruhstaller T, Giobbie-Hurder A, Colleoni M, et al. for the members of the BIG 1-98 Collaborative Group and the International Breast Cancer Study Group. Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer: long-term follow-up of the BIG 1-98 trial. J Clin Oncol. 37(2):105-114, 2019.
4. Morden JP, Alvarez I, Bertelli G, et al. Long-term follow-up of the Intergroup Exemestane Study. J Clin Oncol. 35(22):2507-2514, 2017.
5. 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.
6. 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.
7. Aihara T, Yokota I, Hozumi Y, et al. Anastrozole versus tamoxifen as adjuvant therapy for Japanese postmenopausal patients with hormone-responsive breast cancer: efficacy results of long-term follow-up data from the N-SAS BC 03 trial. Breast Cancer Res Treat. 148(2):337-43, 2014.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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 08/09/24