# Presentation: 684543

## Study of Tamoxifen and RaloxifeneSTAR

**Larry Wickerham, MD**
**NSABP STAR Project Officer**

## NSABP P1 Study

**                 ****# Events**
**Placebo****	****93**
**Tamoxifen****	****60****   **

**                 ****# Events**
**Placebo****	****250**
**Tamoxifen****	****145****   **

**50**

**40**

**30**

**20**

**10**

**0**

**Cumulative Rate/1000**

**Invasive **
**Breast Cancer**

**Noninvasive**
**Breast Cancer**

**Time to Breast Cancer (Years)**

**P < 0.0001**

**P= 0.008**

**NSABP P1 Study**

## Study DesignSTAR

- Age
- Gail Model Risk
- Race
- History of LCIS
- Hysterectomy

- Tamoxifen
- 20 mg/day
- x 5 years

**Study Design****STAR**

- Raloxifene
- 60 mg/day
- x 5 years

- Risk-Eligible Postmenopausal Women

## Inclusion and Exclusion CriteriaSTAR

_**Inclusion**_
- At least 35 years of age
- Postmenopausal
- Risk eligible
- 	Lobular carcinoma *in situ* or
- 	5-year Gail risk of breast cancer _>_1.66%

_**Exclusion**_
- History of:
- Invasive breast cancer
- Ductal carcinoma *in situ*
- DVT, PE
- CVA, TIA
- Uncontrolled diabetes, hypertension or atrial fibrillation

## Primary AimsSTAR

- The primary aim of the study was to determine which  of the following three statements is true:
- Compared to tamoxifen, raloxifene significantly reduces the incidence rate of IBC
- Compared to raloxifene, tamoxifen significantly reduces the incidence rate of IBC
- The statistical superiority of one of the treatments cannot be demonstrated and the choice of therapy should be based on benefit/risk considerations

## Primary ObjectiveSTAR

- Evaluate the effect of raloxifene versus tamoxifen in reducing the incidence of invasive breast cancer in postmenopausal women who are at increased risk.

## Secondary Objectives STAR

- Non-invasive breast cancer
- Endometrial cancer
- Ischemic heart disease
- Fractures of the hip, spine or wrist
- Toxicity and side effects

## Screening, Accrual and Follow-upSTAR

- Screened	184,460
- Eligible	96,368
- Randomized	19,747
- Woman-years of follow-up	79,173
- Average follow-up (years) 	4.06

## Baseline CharacteristicsSTAR

**Baseline Characteristics****STAR**

- Age (mean)	58.5
- Caucasian	93%
- Hysterectomy	51%
- First degree relative(s)with breast cancer	71%
- History of
- 	Lobular carcinoma *in situ*	9%
- 	Atypical hyperplasia	23%
- 5-year predicted Gail risk ofinvasive breast cancer (mean)	4.03%

## Effects on Invasive Breast Cancer STAR

**RR (95% CI) = 1.02 (0.82, 1.27)**

## Invasive Breast Cancer STAR

**168**

**173**

**325**

## Invasive Breast Cancer by 5-year Predicted RiskSTAR

## Invasive Breast Cancer Tumor CharacteristicsSTAR

|  | Tamoxifenn=168 | Raloxifenen=173 |
| --- | --- | --- |
| Estrogen Receptor Status |  |  |
| 	+ | 72% | 69% |
| 	- | 28% | 31% |
| Tumor Size |  |  |
| 	<1 | 29% | 39% |
| 	1.1-3 | 61% | 54% |
| 	>3.1 | 10% | 8% |
| Nodal Status |  |  |
| 	- | 74% | 80% |
| 	+ | 26% | 20% |

## Invasive Breast Cancer in Women with aHistory of LCIS or Atypical Hyperplasia STAR

**Invasive Breast Cancer in Women with a****History of LCIS or Atypical Hyperplasia ****STAR**

## Non-Invasive Breast Cancer STAR

## Non-Invasive Breast CancerSTAR

|  | Tamoxifen
(n) | Raloxifene
(n) | RR (95%CI) |
| --- | --- | --- | --- |
| DCIS | 
32 
 | 47 | 1.46 (0.91-2.37) |
| LCIS | 23  | 29  | 1.26 (0.70-2.27) |
| Mixed | 5  | 7  | 1.39 (0.38-5.57) |

## Uterine Cancer STAR

## Uterine Hyperplasia and HysterectomySTAR

|  | Tamoxifen(n) | Raloxifene(n) | RR (95% CI) |
| --- | --- | --- | --- |
| Hysterectomyduring study | 246 | 92 | 0.37 (0.28, 0.47) |
| Hyperplasia  | 100 | 17 | 0.17 (0.09, 0.28) |
| 	with atypia | 15 | 2 | 0.13 (0.01, 0.56) |
| 	w/o atypia | 85 | 15 | 0.17 (0.09, 0.30) |

**Uterine Hyperplasia and Hysterectomy****STAR**

##  Ischemic Heart Disease STAR

|  | Tamoxifen
(n) | Raloxifene
(n) | RR (95% CI) |
| --- | --- | --- | --- |
| Myocardial infarction | 53 | 39 | 0.73 (0.47-1.13) |
| Severe angina | 55 | 71 | 1.28 (0.89-1.86) |
| Acute ischemic syndrome | 17 | 28 | 1.64 (0.87-3.19) |
| Total | 125 | 138 | 1.10 (0.86-1.41) |

## Osteoporotic Fractures STAR 

| 
 | Tamoxifen
(n) | Raloxifene
(n) | RR (95% CI) |
| --- | --- | --- | --- |
| Hip | 28 | 26 | 0.92 (0.52-1.63) |
| Spine   | 58 | 58 | 0.99 (0.68-1.46) |
| Wrist | 27 | 27 | 0.99 (0.56-1.76) |
| Total* | 111 | 108 | 0.97 (0.73-1.27) |

- *Columns not additive because one patient may have had fractures at multiple sites.

## MortalitySTAR

|  | Tamoxifen(n) | Raloxifene(n) |  |
| --- | --- | --- | --- |
| Cancer | 52 | 52 |  |
| 	Breast cancer | 	5 | 	2 |  |
| Circulatory/vascular  | 25 | 21 |  |
| Other | 32 | 31 |  |
| Any cause | 109 | 104 | RR (95% CI) 0.95 (0.72-1.25) |

## Venous Thromboembolic EventsSTAR

## Cataracts and Cataract Surgery During Follow-upSTAR

## Summary STAR

- Compared with tamoxifen, raloxifene was:
- similar in decreasing the risk of invasive breast cancer
- not as effective at decreasing the risk of non-invasive breast cancer
- associated with fewer:
- adverse events related to uterus
- VTEs
- cataracts and cataract surgery