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,

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

Risk-EligiblePostmenopausal Women

STRATIFICATION• Age• Gail Model Risk• Race• History of LCIS

TAMOXIFEN20 mg/dayx 5 years

NSABP STAR Schema

RALOXIFENE60 mg/dayx 5 years

STAR Trial Objectives

Evaluate the effect of raloxifene vs. tamoxifen in reducing the incidence of:

• Invasive breast cancer

Primary objective:

STAR Trial Objectives

• Noninvasive breast cancer

• Endometrial cancer

• Ischemic Heart Disease

• Fractures of the:– Hip– Spine– Wrist (Colles’)

Secondary objectives:

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) 47.3

76,828

19,747

96,368

184,460

P-2 STAR

Age Distribution

9% 9%

50-5950%

60-6932%

<4970+

P-2 STARRacial/Ethnic Distribution (%)

TAM RAL

White 93.5 93.5

African-American

2.0 2.0

Hispanic 2.4 2.5

Other 2.1 2.1

P-2 STAR 5-year Predicted Risk of Breast Cancer

among Participants at Entry

Gail model risk score

5+27%

2 to 330%

<2

3 to 532%

11%

P-2 STAR First-Degree Relatives

with Breast Cancer

None29%

152%2

16%

3+3%

P-2 STAR

Prior Hysterectomy 51.5%

(10,027)

P-2 STAR

1,789

9.2

LCISLCIS

4426

22.7

AtypicalAtypicalHyperplasiaHyperplasia

Total Number

% ofRandomized

RESULTS

0

2

4

6

8

10

Gail ModelProjection

TAM Raloxifene

Av

An

n R

ate

per

100

0

P-2 STARAverage Annual Rate and

Number of Invasive Breast Cancers

163 168

* # of events

312*

P-2 STARCumulative Incidence ofInvasive Breast Cancer

Cu

mu

lati

ve In

cid

enc

e (p

er

100

0)

Time Since Randomization (months)

At Risk by Year # of Rate/1000Treatment 0 3 6 Events at 6 yrs. P-value

Tamoxifen 9726 6653 809 163 25.1 0.83Raloxifene 9745 6703 833 168 24.8

0

5

10

15

20

25

30

35

40

0 6 12 18 24 30 36 42 48 54 60 66 72

0

1

2

3

4

5

6

7

8

<3 3 to 5 5+

Percent in 5 Years

Av

An

n R

ate

per

100

0 Tamoxifen

Raloxifene

P-2 STARAverage Annual Rate and Number of Invasive

Breast Cancers by 5-year Gail Model Risk

32

61

70

44

47

77

P-2 STAREstrogen Receptor of Invasive Cancers

72

28

68

32

0

20

40

60

80

100

Positive Negative

Per

cen

t

Tamoxifen

Raloxifene

P-2 STARTumor Size (cm) of Invasive Cancers

30

61

9

37

8

55

0

20

40

60

80

100

<1 1.1 to 3 >3

Per

cen

t

TamoxifenRaloxifene

P-2 STARNodal Status of Invasive Cancers

76

24

80

20

0

20

40

60

80

100

Negative Positive

Pe

rce

nt

TamoxifenRaloxifene

0

1

2

3

TAM Raloxifene

Av

An

n R

ate

per

100

0

P-2 STARAverage Annual Rate And Number Of

Non-invasive (In Situ) Cancers

57*

80

* # of events

Relative risk = 1.4095% Confidence Interval: 0.98 to 2.00

P-2 STARCumulative Incidence of

Non-Invasive Breast Cancer

Cu

mu

lati

ve In

cid

enc

e (p

er

100

0)




0

5

10

15

20

25

30

35

40

0 6 12 18 24 30 36 42 48 54 60 66 72

Average Annual Rate of Non-Invasive Breast Cancer by Treatment Group

TumorType

# ofEvents

Rate per1000

RiskRatio

RR 95%Confidence

IntervalTAM RAL TAM RAL

DCIS 30 44 0.79 1.16 1.46 0.90-2.41

LCIS 21 29 0.56 0.76 1.37 0.76-2.54

Mixed 6 7 0.16 0.18 1.16 0.33-4.18

Total 57 80 1.51 2.11 1.40 0.98-2.00

0

3

6

9

12

LCIS1789

AH4426

Av

An

n R

ate

per

100

0

33 33

4641

P-2 STARAverage Annual Rate and Number of Invasive Breast

Cancers by History of Atypical Hyperplasia and Lobular Carcinoma in Situ

TamoxifenRaloxifene

0

1

2

3

TAM Raloxifene

Av

An

n R

ate

per

100

0


Number of Uterine Cancers

36*

23

* # of events

RR = 0.62, 95% CI: 0.35 to 1.08

P-2 STARCumulative Incidence of Uterine Cancer

Cu

mu

lati

ve In

cid

enc

e (p

er

100

0)




0

5

10

15

20

25

30

35

40

0 6 12 18 24 30 36 42 48 54 60 66 72

TAM RAL

Hyperplasia 84 14

with Atypia 12 1

w/o Atypia 72 13

P-2 STAREndometrial Hyperplasia

# of Hysterectomies forNon-Cancer Reasons

TAM RAL

244 111

P-2 STARCumulative Incidence ofThromboembolic Events

Cu

mu

lati

ve In

cid

enc

e (p

er

100

0)


At Risk by Year # of Rate/1000Treatment 0 3 6 Events at 6 yrs. RR


P-value= 0.01

0

5

10

15

20

25

30

35

40

0 6 12 18 24 30 36 42 48 54 60 66 72

0

1

2

3

TAM Raloxifene

Av

An

n R

ate

per

100

0


Number of Strokes

53* 51

* # of events

P-2 STARNumber of Ischemic Heart Disease Events

Type ofType ofeventevent

TamoxifenTamoxifen##

RaloxifeneRaloxifene##

Risk Risk RatioRatio(RR)(RR)

RR 95%RR 95%ConfidenceConfidence

IntervalInterval

Myocardial infarction 48 37 0.77 0.48-1.20

Severe Angina 51 63 1.23 0.84-1.81

Acute ischemic syndrome

15 26 1.72 0.88-3.50

P-2 STARNumber of Osteoporotic Fractures by Site and

Treatment Group

Type of Type of eventevent

TamoxifenTamoxifen##

RaloxifeneRaloxifene##

RiskRiskRatioRatio(RR)(RR)

RR 95%RR 95%ConfidenceConfidence

IntervalInterval

Hip 26 23 0.88 0.48-1.60

Spine 53 52 0.98 0.65-1.46

Radius(Colles’)

Total

27

106

23

98

0.85

0.92

0.46-1.53

0.69-1.22

0

2

4

6

8

10

12

14

TAM Raloxifene

Av

ann

rat

e p

er 1

000

P-2 STARAverage Annual Rates of Cataracts

394*

313

RR = 0.79; 95% CI 0.68 – 0.92

P-2 STARSummary

• 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

Documents

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,