> Table 28: Chemoprevention—the use of tamoxifen and raloxifene to reduce the risk of breast cancer
This summary table contains detailed information about research studies. While viewing summary tables offers an informative glimpse at the science behind many breast cancer guidelines and recommendations, they should be viewed with some caution. There are a number of concepts you must understand to be able to successfully read and interpret research tables. To get some background information about understanding research tables, please see How to Read a Research Table.
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Introduction: 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. A recent meta-analysis further supports the role of tamoxifen as a preventive therapy for breast cancers, especially those that are estrogen receptor-positive [3]. However, tamoxifen may not benefit women with estrogen receptor-negative cancers [3]. Although two studies have found no benefit from tamoxifen, these studies were smaller and less scientifically sound than the NSABP and IBIS trials [4,5]. 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].
The osteoporosis drug, raloxifene, first showed promise as a chemopreventive drug in the Multiple Outcomes for Raloxifene Evaluation (MORE) trial and its companion follow-up study 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]. In September 2007, the U.S. Food and Drug Administration approved the use of raloxifene for the prevention of invasive breast cancer among postmenopausal women at high risk*.
*High risk is defined as having at least a 16.7 in 1,000 chance of getting breast cancer in the next five years, as calculated by the Gail model [10]. For more on the Gail model, visit the Risk Factors and Prevention section.
Study selection criteria: Available randomized controlled trials.
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 either 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
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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
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Tamoxifen
(20mg/day) for 5 years
|
39.7 per 1,000
|
54.5 per 1,000
|
0.73
(0.58-0.91)
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Italian Tamoxifen Prevention Study [4]
|
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)
|
Royal Marsden Hospital, UK [5]
|
2,471 women, aged 30-70, with a family history of breast cancer
|
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)
|
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 [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
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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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* 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. Cuzick J, Powles T, Veronesi U, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 361: 296-300, 2003.
4. 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.
5. 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.
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 09/12/09
