> Table 28: Chemoprevention—the use of tamoxifen and raloxifene to reduce the risk of breast cancer
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Introduction: Chemoprevention is the use of drugs to lower the risk of breast cancer in women at higher risk. Tamoxifen and raloxifene are the only two drugs FDA-approved for breast cancer chemoprevention. Both pre- and postmenopausal women can take tamoxifen. Only postmenopausal women can take raloxifene.
Tamoxifen
There is strong evidence from two large randomized controlled trials that tamoxifen can reduce the risk of breast cancer [1,2]. Both the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the International Breast Cancer Intervention Study (IBIS) showed that tamoxifen lowered risk in women at high risk* for breast cancer. Although two other randomized controlled trials found no benefit from tamoxifen, these studies were smaller and less scientifically sound than the NSABP and IBIS trials [3,4].
A meta-analysis further supports the role of tamoxifen as a risk-lowering drug for estrogen receptor-positive breast cancer [5]. Tamoxifen may not lower the risk of estrogen receptor-negative breast cancer [5].
Despite evidence that tamoxifen can lower the risk of breast cancer, it has some health risks and is not recommended for all women [1,6]. Learn more about the health risks of tamoxifen.
Raloxifene
The osteoporosis drug, raloxifene, first showed promise as a chemoprevention drug in the Multiple Outcomes for Raloxifene Evaluation (MORE) trial and its follow-up study the Continuing Outcomes Relevant to Evista (CORE) trial [7,8]. Results from the NSABP's STAR P-2 Trial found raloxifene to be as good as tamoxifen in reducing the risk of invasive breast cancer [9]. A meta-analysis also found raloxifene reduced the risk of estrogen receptor-positive breast cancer, but may not lower the risk of estrogen receptor-negative breast cancer [5].
Raloxifene is only used for chemoprevention in postmenopausal women and is not given to premenopausal women.
Despite evidence that raloxifene can lower the risk of postmenopausal breast cancer, it has some health risks and is not recommended for all women [5]. 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) [10]. For more on the Breast Cancer Risk Assessment Tool, visit the Risk Factors and Prevention section.
Study selection criteria: Available randomized controlled trials and meta-analyses with at least 500 participants.
Table note: Relative risk above 1 indicates increased risk. Relative risk below 1 indicates decreased risk.
Study
|
Study Population
|
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) [1]
|
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)
|
IBIS-I Trial (International Breast Cancer Intervention Study) [2]
|
7,154 women aged 35 to 70, at high risk
|
8
|
Tamoxifen
(20mg/day) for 5 years
|
39.7 per 1,000
|
54.5 per 1,000
|
0.73
(0.58-0.91)
|
Italian Tamoxifen Prevention Study [3]
|
5,408 women, aged 35-70, who had hysterectomy
|
11.2
|
Tamoxifen
(20mg/day)
|
27.3 per 1,000
|
23.0 per 1,000
|
0.84
(0.60-1.17)
|
Royal Marsden Hospital, UK [4]
|
2,471 women, aged 30-70, with a family history of breast cancer
|
13
|
Tamoxifen
(20mg/day) for 8 years
|
66.2 per 1,000
|
84.3 per 1,000
|
0.78
(0.58-1.04)
|
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)
|
RUTH (Raloxifene Use for The Heart) trial [11]
|
10,101 postmenopausal women, age 55 or older, with heart disease or at risk for heart disease
|
5.6
|
Raloxifene
(60mg/day)
|
13.8 per 1,000
|
7.9 per 1,000
|
0.56
(0.38-0.83)
|
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
|
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) [9]
|
19,747 postmenopausal women at high risk
|
3.9
|
Raloxifene (60mg/day)
Tamoxifen(20mg/day)
|
4.41
|
4.30
|
1.02
(0.82-1.28)
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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. [5] |
4 studies |
Tamoxifen |
0.70
(0.59-0.82) |
| |
2 studies |
Raloxifene |
0.44
(0.27-0.71) |
* In addition to years of participation in the MORE trial.
References
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Freedman AN, Graubard BI, Rao SR, McCaskill-Stevens W, Ballard-Barbash R, Gail MH. Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention. J Natl Cancer Inst. 95(7):526-32, 2003.
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 Research and Treatment 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. Vogel VG, Costantino JP, Wickerham DL, et al. for the National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs. raloxifene on the risk of developing invasive breast cancer and other disease outcomes: The NSABP study of tamoxifen and raloxifene (STAR) P-2 Trial. JAMA. 295(23):2727-2741, 2006.
10. 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.
11. 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.
Updated 03/10/10
