> Table 29: Chemoprevention—the use of tamoxifen and raloxifene to reduce the risk of 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.
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Introduction: Chemoprevention is the use of drugs to lower the risk of breast cancer in women who do not have breast cancer but are at higher risk. Tamoxifen and raloxifene are the only two drugs FDA-approved for breast cancer chemoprevention.
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 and raloxifene only reduce the risk of estrogen receptor-positive breast cancers. Neither drug reduces the risk of estrogen receptor-negative cancers.
Tamoxifen
Both pre- and postmenopausal women can take tamoxifen.
Tamoxifen is related to some health risks and is not recommended for all women [1-2]. Learn more about the health risks of tamoxifen.
Raloxifene
Raloxifene is only used for chemoprevention in postmenopausal women and is not given to premenopausal women.
Raloxifene has fewer harmful side effects than tamoxifen and may be a better choice for some women [1]. Learn more 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 five years, as calculated by the Breast Cancer Risk Assessment Tool (the Gail model) [3]. Learn more about the Breast Cancer Risk Assessment Tool.
Study selection criteria: Randomized controlled trials with at least 500 participants and meta-analyses.
Table note: Relative risk above 1 indicates increased risk. Relative risk below 1 indicates decreased risk.
Study
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Study Population
(number of participants)
|
Median Follow-up
(years)
|
Drug Used
(dosage)
|
Absolute Risk of
Invasive Breast Cancer
(number of cases per 1,000 women)
|
Relative Risk of Invasive Breast Cancer in Women Taking Tamoxifen or Raloxifene Compared to Women Taking Placebo
RR (95% CI)
|
Among Women Taking Placebo
|
Among Women Taking the Drug Used in the Study
|
Randomized controlled trials of tamoxifen versus placebo
|
NSABP P-1 (National Surgical Adjuvant Breast and Bowel Project) [2]
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13,388 women
aged 35 and over,
at high risk
|
7
|
Tamoxifen
(20mg/day) for 5 years
|
42.5 per 1,000
|
24.8 per 1,000
|
0.57
(0.46-0.70)
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IBIS-I Trial (International Breast Cancer Intervention Study) [4]
|
7,154 women
aged 35 to 70,
at high risk
|
8
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Tamoxifen
(20mg/day) for 5 years
|
39.7 per 1,000
|
54.5 per 1,000
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0.73
(0.58-0.91)
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Italian Tamoxifen Prevention Study [5]
|
5,408 women
aged 35-70,
who had hysterectomy
|
11.2
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Tamoxifen
(20mg/day)
|
27.3 per 1,000
|
23.0 per 1,000
|
0.84
(0.60-1.17)
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Royal Marsden Hospital, UK [6]
|
2,471 women
aged 30-70,
with a family history of breast cancer
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13
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Tamoxifen
(20mg/day) for 8 years
|
66.2 per 1,000
|
84.3 per 1,000
|
0.78
(0.58-1.04)
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Randomized controlled trials of raloxifene versus placebo
|
MORE Trial (Multiple Outcomes for Raloxifene Evaluation) [7]
|
7,705 postmenopausal women
younger than age 81,
with osteoporosis
|
4.0
|
Raloxifene
(60mg or 120mg/day)
|
4.7 per 1,000
|
1.3 per 1,000
|
0.28
(0.17-0.46)
|
CORE Trial (Continuing Outcomes Relevant to Evista) [8]
|
5,213 postmenopausal women
with osteoporosis
who were participants in the MORE trial
|
4.0*
|
Raloxifene
(60mg/day)
|
5.2 per 1,000
|
2.1 per 1,000
|
0.41
(0.24-0.71)
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RUTH (Raloxifene Use for The Heart) trial [9]
|
10,101 postmenopausal women
age 55 or older,
with heart disease or
at risk for heart disease
|
5.6
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Raloxifene
(60mg/day)
|
13.8 per 1,000
|
7.9 per 1,000
|
0.56
(0.38-0.83)
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Study
|
Study Population
(number of participants)
|
Median Follow-up
(years)
|
Drug Used
(dosage)
|
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
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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
|
6.8
|
Raloxifene (60mg/day)
Tamoxifen(20mg/day)
|
5.02
|
4.04
|
1.24
(1.05-1.47)
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Study
|
Number of Studies in Analysis
|
Drug Used
|
Relative Risk of Invasive Breast Cancer
in Women Taking Tamoxifen or Raloxifene
Compared to Women Taking Placebo
RR (95% CI)
|
Meta-analyses of tamoxifen or raloxifene versus placebo
|
Nelson et al. [10]
|
4 studies
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Tamoxifen
|
0.70
(0.59-0.82)
|
| |
2 studies |
Raloxifene
|
0.44
(0.27-0.71)
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* In addition to years in the MORE trial.
References
- 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.
- 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.
- 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.
- Cuzick J, Forbes JF, Sestak I, et al. for the International Breast Cancer Intervention Study I (IBIS-I) Investigators. Long-term results of tamoxifen prophylaxis for breast cancer—96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst. 21;99(4):272-82, 2007.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Updated 01/22/13
