The Who, What, Where, When and Sometimes, Why.

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 percent and raloxifene by about 38 percent) 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 pre- 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.

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.

*High risk is defined as having a 1.67 percent 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

0.70
(0.59-0.82)

 

2 studies

Raloxifene

0.44
(0.27-0.71)

* 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, Griffin JC, Nygren P, Smith ME, Humphrey L. Systematic review: Comparative effectiveness of medications to reduce risk for primary breast cancer. Ann Intern Med. 151(10):703-715, 2009.

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