The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 6, 2006

Presenter: D. L. Wickerham
Presenter's Affiliation: National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA
Type of Session: Plenary

Background

The NSABP-P1 study demonstrated that tamoxifen given to high-risk pre- and post-menopausal women decreased the risk of both invasive and non-invasive breast cancers
- There was an increased incidence of uterine cancers in the tamoxifen arm compared to the placebo arm
Raloxifene is a selective estrogen receptor modulator (SERM) that is approved for osteoporosis indications that was predicted to have a decreased risk of endometrial tumorigenesis
The STAR trial is a large chemoprevention trial of tamoxifen vs. raloxifene in high-risk post-menopausal women

Materials and Methods

Randomized, double-blind, randomized to:
- Tamoxifen 20 mg daily x 5 yr
- Raloxifene 60 mg daily x 5 yr
Criteria:
- post-menopausal
- Modified Gail risk model: 5-yr predicted breast cancer risk of 1.66%
- Excluded women with prior history of DVT, pulmonary embolism, stroke, TIA, and uncontrolled atrial fibrillation/hypertension/diabetes
Endpoints:
- Primary: Invasive breast cancer incidence
- Secondary: Non-invasive breast cancer incidence, endometrial cancer incidence, ischemic heart disease, fractures (hip, spine, wrist)
Planned reporting after 327 invasive breast cancer cases total

Results

184,460 were screened; 96,368 eligible for study; 19,747 were randomized
Baseline characteristics were well balanced between the groups
- mean age = 58. Only 9% were < 49 yr
- mean 5-yr risk of breast cancer = 4.04%
- 71% had at least one 1st degree relative with breast cancer
- 93.5% were white. There were twice as many minorities enrolled on this study compared to the P1 trial
- 51.5% had prior hysterectomy
Average time on study was 47 months
Invasive breast cancer rate:
- Tamoxifen and raloxifene were equally effective in reducing the rate of invasive breast cancer (163 Tam, 168 Ral) compared to the predicted placebo rate (312).
- RR = 1.02, 95% CI 0.82-1.27)
- No differences were observed between the tumor characteristics of the invasive breast cancers that did develop (70% ER+, 76-80% node negative)
- Non-invasive breast cancer rate:
- Tamoxifen decreased the rate of non-invasive breast carcinoma more than raloxifene (57 Tam, 81 Ral)
- RR = 1.41, 95% CI 1.00-2.02
Uterine cancer rate:
- 40% fewer endometrial cancers in raloxifene arm (36 Tam, 23 Ral), which did not reach significance
- RR 0.62, 95% CI 0.35-1.08
There were fewer thromboembolic events in raloxifene arm
- DVT: RR = 0.7, p=0.01
- fewer pulmonary emboli (0.9 vs. 1.4/1000 patients/year)
There were fewer cataracts in raloxifene arm
There was no significant difference in any other invasive cancer site, cardiac events, osteoporotic fractures, or deaths.

Author's Conclusions

Raloxifene is an effective alternative to tamoxifen in reducing the incidence of invasive breast cancer in postmenopausal women at high risk for developing breast cancer
Raloxifene was associated with fewer endometrial cancers, DVT’s, and pulmonary emboli

Clinical/Scientific Implications

In postmenopausal women at high risk for developing breast cancer, raloxifene and tamoxifen are equally effective at reducing the incidence of invasive breast cancer, but tamoxifen was more effective at reducing the incidence of non-invasive breast cancer.
The rate of endometrial cancers was greater in the tamoxifen arm, but this difference did not reach significance
Raloxifene was associated with a lower risk of thromboembolic events
In deciding which agent to choose for preventing breast cancer in high-risk postmenopausal women, the many factor can be considered:
- Prior hysterectomy
- Acceptance of risk of non-invasive breast cancer
- Risk of thromboembolic events (the study patients were highly selected to have low risk)
- Side-effect profiles of tamoxifen and raloxifene
- Cost