1. Study of Tamoxifen and Raloxifene (STAR): Initial Findings from the NSABP P-2 Breast Cancer Prevention Study
D.L. Wickerham, J.P. Costantino, V. Vogel,
W.M. Cronin, R.S. Cecchini, J. Atkins, T. Bevers,
L. Fehrenbacher, W. McCaskill-Stevens, N. Wolmark
ASCO 2006

3. NSABP STAR Schema STRATIFICATION TAMOXIFEN 20 mg/day x 5 years
Risk-Eligible
Postmenopausal Women
STRATIFICATION
Age
Gail Model Risk
Race
History of LCIS
TAMOXIFEN
20 mg/day
x 5 years
RALOXIFENE
60 mg/day
x 5 years

4. STAR Trial Objectives Primary objective:
Evaluate the effect of raloxifene vs. tamoxifen in reducing the incidence of:
Invasive breast cancer

5. STAR Trial Objectives Secondary objectives: Noninvasive breast cancer
Endometrial cancer
Ischemic Heart Disease
Fractures of the:
Hip
Spine
Wrist (Colles’)

6. STAR Summary of Screening, Accrual and Follow-Up Information
Women screened for breast cancer risk
Women who were breast cancer risk eligible
Women randomly assigned treatment
Total person-years of follow-up
Average follow-up (months)
184,460
96,368
19,747
76,828
47.3

7. P-2 STAR Age Distribution9%
50-59
50%
60-69
32%
<49
70+

8. P-2 STAR Racial/Ethnic Distribution (%)
TAM
RAL
White
93.5
African-American
2.0
Hispanic
2.4
2.5
Other
2.1

9. P-2 STAR 5-year Predicted Risk of Breast Cancer among Participants at Entry5+
27%
11%
<2
2 to 3
30%
3 to 5
32%
Gail model risk score

10. P-2 STAR First-Degree Relatives with Breast Cancer
None
29% 3+ 3% 1
52% 2
16%

11. P-2 STAR
Prior Hysterectomy 51.5%
(10,027)

12. P-2 STAR Atypical Hyperplasia LCIS Total Number % of Randomized 1,789
9.2
4426
22.7

13. RESULTS

14. P-2 STAR Average Annual Rate and Number of Invasive Breast Cancers2 4 6 8 10
Gail Model
Projection
TAM
Raloxifene
Av Ann Rate per 1000
312*
163
168
* # of events

15. P-2 STAR Cumulative Incidence of Invasive Breast Cancer5 10 15 20 25 30 35 40 6 12 18 24 36 42 48 54 60 66 72
At Risk by Year # of Rate/1000
Treatment Events at 6 yrs. P-value
Tamoxifen
Raloxifene
Cumulative Incidence (per 1000)
Time Since Randomization (months)

16. P-2 STAR Average Annual Rate and Number of Invasive Breast Cancers by 5-year Gail Model Risk8 7
Tamoxifen 77 70 6
Raloxifene 5 61
Av Ann Rate per 1000 4 47 3 44 2 32 1
<3
3 to 5 5+
Percent in 5 Years

17. P-2 STAR Estrogen Receptor of Invasive Cancers72 28 68 32 20 40 60 80
100
Positive
Negative
Percent
Tamoxifen
Raloxifene

18. P-2 STAR Tumor Size (cm) of Invasive Cancers30 61 9 37 8 55 20 40 60 80
100
<1
1.1 to 3
>3
Percent
Tamoxifen
Raloxifene

19. P-2 STAR Nodal Status of Invasive Cancers76 24 80 20 40 60
100
Negative
Positive
Percent
Tamoxifen
Raloxifene

20. 95% Confidence Interval: 0.98 to 2.00
P-2 STAR Average Annual Rate And Number Of Non-invasive (In Situ) Cancers 1 2 3
TAM
Raloxifene
Av Ann Rate per 1000
Relative risk = 1.40
95% Confidence Interval: 0.98 to 2.00 80
57*
* # of events

21. P-2 STAR Cumulative Incidence of Non-Invasive Breast Cancer5 10 15 20 25 30 35 40 6 12 18 24 36 42 48 54 60 66 72
At Risk by Year # of Rate/1000
Treatment Events at 6 yrs. P-value
Tamoxifen
Raloxifene
Cumulative Incidence (per 1000)
Time Since Randomization (months)

22. Average Annual Rate of Non-Invasive Breast Cancer by Treatment Group
 Tumor
Type
# of
Events
Rate per
1000
Risk
Ratio
RR 95%
Confidence
Interval
TAM
RAL
DCIS 30 44
0.79
1.16
1.46
LCIS 21 29
0.56
0.76
1.37
Mixed 6 7
0.16
0.18
Total 57 80
1.51
2.11
1.40

23. P-2 STAR Average Annual Rate and Number of Invasive Breast Cancers by History of Atypical Hyperplasia and Lobular Carcinoma in Situ 3 6 9 12
Tamoxifen
Raloxifene 33 33
Av Ann Rate per 1000 46 41
LCIS
1789 AH
4426

24. P-2 STAR Average Annual Rate and Number of Uterine Cancers1 2 3
TAM
Raloxifene
Av Ann Rate per 1000
RR = 0.62, 95% CI: 0.35 to 1.08
36* 23
* # of events

25. P-2 STAR Cumulative Incidence of Uterine Cancer5 10 15 20 25 30 35 40 6 12 18 24 36 42 48 54 60 66 72
At Risk by Year # of Rate/1000
Treatment Events at 6 yrs. P-value
Tamoxifen
Raloxifene
Cumulative Incidence (per 1000)
Time Since Randomization (months)

26. Endometrial Hyperplasia
P-2 STAR
Endometrial Hyperplasia
TAM
RAL
Hyperplasia 84 14
with Atypia 12 1
w/o Atypia 72 13

27. # of Hysterectomies for Non-Cancer Reasons
TAM RAL

28. P-2 STAR Cumulative Incidence of Thromboembolic Events5 10 15 20 25 30 35 40 6 12 18 24 36 42 48 54 60 66 72
At Risk by Year # of Rate/1000
Treatment Events at 6 yrs. RR
Tamoxifen
Raloxifene
P-value= 0.01
Cumulative Incidence (per 1000)
Time Since Randomization (months)

29. P-2 STAR Average Annual Rate and Number of Strokes1 2 3
TAM
Raloxifene
Av Ann Rate per 1000
53* 51
* # of events

30. P-2 STAR Number of Ischemic Heart Disease Events
Type of
event
Tamoxifen #
Raloxifene
Risk
Ratio
(RR)
RR 95%
Confidence
Interval
Myocardial infarction 48 37
0.77
Severe Angina 51 63
1.23
Acute ischemic syndrome 15 26
1.72

31. P-2 STAR Number of Osteoporotic Fractures by Site and Treatment Group
Type of event
Tamoxifen #
Raloxifene
Risk
Ratio
(RR)
RR 95%
Confidence
Interval
Hip 26 23
0.88
Spine 53 52
0.98
Radius
(Colles’)
Total 27
106 98
0.85
0.92

32. P-2 STAR Average Annual Rates of Cataracts2 4 6 8 10 12 14
TAM
Raloxifene
Av ann rate per 1000
RR = 0.79; 95% CI 0.68 – 0.92
394*
313

33. Fewer thromboembolic events Fewer endometrial cancers and
P-2 STAR Summary
Raloxifene is as effective as tamoxifen in the prevention of primary invasive breast cancer
Raloxifene is less effective than tamoxifen in the prevention of non-invasive breast cancer (LCIS & DCIS)
Compared to tamoxifen, raloxifene use results in:
Fewer thromboembolic events
Fewer endometrial cancers and
Fewer cataracts