# Presentation: 837016

## Risk Benefit and Conclusions

**George Sledge, MD****Indiana University School of Medicine**

## Do We Need a New Chemoprevention Agent?

- Breast cancer continues to represent a major cause of morbidity and mortality
- Few women actually receive tamoxifen as chemoprevention for breast cancer
- Real toxicities (VTE, uterine cancer) limit its use
- Perception that it is a “cancer drug” with poor risk/benefit ratio

## Raloxifene Demonstrates Efficacyin Postmenopausal WomenAcross a Spectrum of Breast Cancer Risk

- 71%

- 56%

- 44**%**

- RR 1.02

## Confirmation of Raloxifene’s Effectiveness Relative to Tamoxifen in STAR

- STAR Non-inferiority Analysis
-  	Proportion retention of tamoxifen’s effect* (95% CI) = 97% (65%, 128%)

- STAR Primary Analysis
- RR (95% CI) = 1.02 (0.82, 1.27)

*** Tamoxifen’s effect based on women 50 years or older in P-1**

## Raloxifene as an Alternative to Tamoxifen: Benefit

- Similar efficacy with regard to prevention of invasive breast cancer
- Less effect on noninvasive cancers

## Non-Invasive Breast Cancerin Placebo-Controlled Studies MORE, CORE, RUTH

- 11/5044

- 5/5057

- 2/1274

- 5/2716

**(N=5133)**

**(N=3990)**

**(N=10,101)**

- 5/2576

- 3/2557

**SEER**

**SEER annual US incidence rate per 1,000 in white women ≥50 (2000 data) **

## Efficacy and Important Safety Outcomes STAR

**FAVORS RALOXIFENE**

**FAVORS TAMOXIFEN**

- Difference in Number of Events (95% CI) per 1000 Women/Yr

- P=0.055

- P=0.057

*****

*****

*****

*****

- *P < 0.05 vs. tamoxifen

## Differences in Outcomes forRaloxifene versus TamoxifenSTAR

**(RALOXIFENE VS. TAMOXIFEN)**

- Non-invasive breast cancer	3 more
- 	DCIS only		2 more
- Hysterectomy	40 fewer†
- Hyperplasia	20 fewer†
- Uterine cancer	4 fewer
- Venous thromboembolism	6 fewer†
-      Deep vein thrombosis		3 fewer
-      Pulmonary embolism		3 fewer
- Cataracts	10 fewer†
- 	Cataract surgery		9 fewer†

**Outcome**

- †P < 0.05

**Differences in Outcomes for****Raloxifene versus Tamoxifen****STAR**

## Invasive Breast Cancer Risk Reduction Compares Favorablywith Other Prevention Therapies

- 2MRC Working Party Br Med J 1992;304:405-412
- 3Berger JS et al. JAMA 2006;295:306-313
- 4Fisher B et al., J Natl Cancer Inst. 1998 Sep 16;90(18):1371-88.

**Invasive Breast Cancer Risk Reduction Compares Favorably****with Other Prevention Therapies**

| Therapy | Event | NNT* |
| --- | --- | --- |
| Atorvastatin1 | MI/CHD death	 | 294 |
| Antihypertensives2 | Strokes | 370 |
|  | Coronary event | 417 |
| Aspirin3 | MI | 753 |
| Tamoxifen4 | Invasive BrCa	 | 303 |
| Raloxifene (MORE) | Invasive BrCa	 | 323 |
| Raloxifene (CORE) | Invasive BrCa	 | 335 |
| Raloxifene (RUTH) | Invasive BrCa	 | 862 |

- *NNT = number of patients needed to treat for 1 year to prevent 1 outcome

## Postmenopausal women at high risk for breast cancer should now have a choice

## Well established, FDA approved agent for prevention and treatment of osteoporosis
Reduced risk of invasive breast cancer observed in MORE has been confirmed in RUTH and STAR
Clinically important benefit for these women

- Reduced risk of invasive breast cancer observed in MORE has been confirmed in RUTH and STAR
- Clinically important benefit for these women

**Raloxifene and Postmenopausal Women with Osteoporosis**

## Invasive Breast Cancer and Vertebral Fracture MORE and P-1

**Clinical Vertebral Fracture**
**(No. per 1000/yr)**

**Invasive Breast Cancer **
**(No. per 1000/yr)**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

## Invasive Breast Cancer and Vertebral Fracture MORE and P-1

**Clinical Vertebral Fracture**
**(No. per 1000/yr)**

**Invasive Breast Cancer **
**(No. per 1000/yr)**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

## Invasive Breast Cancer and Vertebral Fracture MORE and P-1

**(No. per 1000/yr)**

**Invasive Breast Cancer **
**(No. per 1000/yr)**

**MORE**

**Placebo**

**P-1 (age≥50)**

**Placebo**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**0**

**2**

**4**

**6**

**8**

**10**

**12**

**Raloxifene**

**3.1 fewer**

**3.6 fewer**

**Tamoxifen**

**0.5 fewer**

**5.2 fewer**

**Invasive Breast Cancer and Vertebral Fracture ****MORE and P-1**

## Postmenopausal women considering raloxifene for treatment of osteoporosis should be informed about the potential additional benefit on their risk of invasive breast cancer

**Slide Modified: **

**Memo: **

## Conclusion

- Since 1998 an estimated 22 million postmenopausal women worldwide have received raloxifene to prevent or treat osteoporosis.
- Clinical trials involving more than 37,000 postmenopausal women now provide information on the benefits and risks of the use of raloxifene to reduce the risk of invasive breast cancer.
- The benefit-risk is favorable in postmenopausal women at high risk for breast cancer and in postmenopausal women taking raloxifene for osteoporosis.