Raloxifene is not as effective as tamoxifen in preventing invasive breast cancer as shown by The Study of Tamoxifen and Raloxifene P-2 (STAR)—the only prevention study evaluating raloxifene for invasive breast cancer as a primary outcome.4 Initial results from STAR showed the two agents were similarly effective in preventing invasive breast cancer.11,13 However, in long-term follow-up, raloxifene had a lesser overall effect than tamoxifen (Table 1).
Table 1. Benefit and Risk in STAR: Evolution Over Time13,14
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| Median Follow-up | No. of Events | Hazard Ratio (95% CI) |
||
| Tamoxifen | Raloxifene | |||
| Benefit: Invasive Breast Cancer | ||||
| 47 months13 | 163 | 168 | 1.02 (0.82-1.28) | |
| 81 months14 | 247 | 310 | 1.24 (1.05-1.47)* | |
*P=0.01.
These drugs have different potential for serious side effects. Tamoxifen stimulates endometrial growth and is associated with increased risk for endometrial cancer in postmenopausal, but not premenopausal, women; long-term results from STAR showed women treated with tamoxifen versus raloxifene were about twice as likely to develop invasive uterine cancer.14 While both drugs increase the risk for thromboembolic events, this side effect occurred at a higher rate with tamoxifen in the long-term results from STAR (Table 2).14
Table 2. Harm in STAR: Evolution Over Time13,14
| Median Follow-up | No. of Events | Hazard Ratio (95% CI) |
||
| Tamoxifen | Raloxifene | |||
| Invasive Uterine Cancer | ||||
| 47 months | 36 | 23 | 0.62 (0.35-1.08) | |
| 81 months | 65 | 37 | 0.55 (0.36-0.83)* | |
| Thromboembolic Events | ||||
| 47 months | 141 | 100 | 0.70 (0.54-0.91)† | |
| 81 months | 202 | 154 | 0.75 (0.60-0.93)‡ | |
*P=0.003; †P=0.01; ‡P=0.007
Aromatase inhibitors (AIs) decrease estrogen levels through reversible (anastrozole) or irreversible (exemestane) inhibition of the aromatase enzyme.16 Data shows these drugs had a larger prevention effect than tamoxifen.4,12
The Mammary Prevention.3 (MAP.3) trial evaluated exemestane (n=2,285) for primary prevention of breast cancer versus placebo (n=2,275). Participants, which excluded BRCA1/2 carriers, were postmenopausal women with one or more breast cancer risk factors. 7 At a median of 35 months follow-up, exemestane treatment resulted in a 65% reduction in invasive breast cancer (P=0.002), which was the primary endpoint of the study.7 Although treatment produced a 73% reduction in ER-positive breast cancer (P<0.001), it had no effect on ER-negative disease. Overall, the treatment also reduced the risk for invasive breast cancer, LCIS, ductal carcinoma in situ (DCIS), and atypical hyperplasia.7
