Research table: Tamoxifen and raloxifene to reduce breast cancer risk

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: Tamoxifen and raloxifene are the only drugs approved by the U.S. Food and Drug Administration (FDA) to lower the risk of breast cancer in women at high risk. The use of risk-lowering drugs may be called chemoprevention, although no chemotherapy is involved.

Both tamoxifen and raloxifene can lower the risk of invasive breast cancer (tamoxifen by about 50% and raloxifene by about 38%) in women at high risk* [1]. 

Both drugs also lower the risk of non-invasive breast cancer, such as ductal carcinoma in situ (DCIS), in women at high risk [1].

Tamoxifen

Both premenopausal and postmenopausal women can take tamoxifen.

Tamoxifen has some health risks and is not recommended for all women [1-2]. Learn about the health risks of tamoxifen.

Learn more about tamoxifen and breast cancer risk reduction.

Raloxifene

Only postmenopausal women can take raloxifene. It’s not given to premenopausal women.

Raloxifene has fewer harmful side effects than tamoxifen and may be a better choice for some women [1]. Learn about the health risks of raloxifene.

Learn more about raloxifene and breast cancer risk reduction.

*High risk is defined as having a 1.67% or greater chance of getting breast cancer in the next 5 years, as calculated by the Breast Cancer Risk Assessment Tool (the Gail model) [3].  

Study selection criteria: Randomized controlled trials with at least 500 participants, pooled analyses and meta-analyses.

Table note: Relative risk above 1 indicates increased risk. Relative risk below 1 indicates decreased risk.  

Study	Study Population (number of participants)	Follow-up (years)	Absolute Risk of Invasive Breast Cancer (number of cases per 1,000 women)		Relative Risk of Invasive Breast Cancer in Women Taking Tamoxifen Compared to Women Taking Placebo, RR (95% CI)
			Among Women Taking Tamoxifen	Among Women Taking Placebo
Randomized controlled trials of tamoxifen versus placebo
NSABP P-1 (National Surgical Adjuvant Breast and Bowel Project) [2]	13,388 women ages 35 and over, at high risk	7	25 per 1,000	43 per 1,000	0.57 (0.46-0.70)
IBIS-I Trial (International Breast Cancer Intervention Study) [4]	7,154 women ages 35-70, at high risk	16	70 per 1,000	98 per 1,000	0.71 (0.60-0.83)
Italian Tamoxifen Prevention Study [5]	5,408 women ages 35-70, who had hysterectomy	11	23 per 1,000	27 per 1,000	0.84 (0.60-1.17)
Royal Marsden Hospital, UK [6]	2,471 women ages 30-70, with a family history of breast cancer	13	84 per 1,000	66 per 1,000	0.78 (0.58-1.04)
Study	Study Population (number of participants)	Follow-up (years)	Absolute Risk of Invasive Breast Cancer (number of cases per 1,000 women)		Relative Risk of Invasive Breast Cancer in Women Taking Raloxifene Compared to Women Taking Placebo, RR (95% CI)
			Among Women Taking Raloxifene	Among Women Taking Placebo
Randomized controlled trials of raloxifene versus placebo
MORE Trial (Multiple Outcomes for Raloxifene Evaluation) [7]	7,705 postmenopausal women with osteoporosis	4	1 per 1,000	5 per 1,000	0.28 (0.17-0.46)
CORE Trial (Continuing Outcomes Relevant to Evista) [8]	5,213 postmenopausal women with osteoporosis	4*	2 per 1,000	5 per 1,000	0.41 (0.24-0.71)
RUTH (Raloxifene Use for The Heart) trial [9]	10,101 postmenopausal women with heart disease or at risk for heart disease	6	8 per 1,000	14 per 1,000	0.56 (0.38-0.83)
Study	Study Population (number of participants)	Follow-up (years)	Absolute Risk of Invasive Breast Cancer (number of cases per 1,000 women)		Relative Risk of Invasive Breast Cancer in Women Taking Raloxifene Compared to Women Taking Tamoxifen, RR (95% CI)
			Among Women Taking Raloxifene	Among Women Taking Tamoxifen
Randomized controlled trials of raloxifene versus tamoxifen
NSABP/STAR P-2 (National Surgical Adjuvant Breast and Bowel Project/Study of Tamoxifen and Raloxifene) [1]	19,490 postmenopausal women at high risk	7	5 per 1,000	4 per 1,000	1.24 (1.05-1.47)
Study	Number of Participants or Studies in Analysis	Drug Studied		Relative Risk of Invasive Breast Cancer in Women Taking Tamoxifen or Raloxifene Compared to Women Taking Placebo, RR (95% CI)
Pooled and meta-analyses of tamoxifen or raloxifene versus placebo
Cuzick et al. [10]	83,399	Tamoxifen		0.67 (0.59-0.76)
		Raloxifene		0.66 (0.55-0.80)
Nelson et al. [11]	4 studies	Tamoxifen		0.69 (0.59-0.84)
	2 studies	Raloxifene		0.44 (0.24-0.80)

* In addition to years in the MORE trial

References 

1. Vogel VG, Costantino JP, Wickerham DL, et al. for the National Surgical Adjuvant Breast and Bowel Project. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res. 3(6):696-706, 2010.
2. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for Prevention of Breast Cancer: Current Status of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 97(22):1652-62, 2005.
3. Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 81(24):1879-1886, 1989.
4. Cuzick J, Sestak I, Cawthorn S, et al. for the IBIS-I Investigators. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 16(1):67-75, 2015.
5. Veronesi U, Maisonneuve P, Rotmensz N, et al. for the Italian Tamoxifen Study Group. Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy. J Natl Cancer Inst. 99(9):727-37, 2007.
6. Powles T, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst. 99(4):283-90, 2007.
7. Cauley JA, Norton L, Lippman ME et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Breast Cancer Res Treat. 65(2):125-143, 2001.
8. Martino S, Cauley JA, Barrett-Connor E, et al. for the CORE Investigators. Continuing Outcomes Relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. 96(23):1751-1761, 2004.
9. Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 355(2):125-37, 2006.
10. Cuzick J, Sestak I, Bonanni B, et al. for the SERM Chemoprevention of Breast Cancer Overview Group. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 381(9880):1827-34, 2013.
11. Nelson HD, Fu R, Zakher B, Pappas M, McDonagh M. Medication use for the risk reduction of primary breast cancer in women: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 322(9):868-886, 2019.

Updated 06/06/24