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Is raloxifene more effective or less effective than tamoxifen in significantly reducing the incidence rate of breast cancer in healthy postmenopausal women?

The STAR Trial

April 26, 2010

Study:  An update of the STAR P-2 trial on preventing breast cancer

Study Design:  A two-arm, randomized, double-blinded phase III trial  

Study Eligibility: Only healthy women who were postmenopausal, at least 35 years of age, and who had 5-year Gail model-predicted breast cancer risk of at least 1.66%

Enrollment:  19,747 healthy postmenopausal women  

The National Surgical Adjuvant Breast and Bowel Projects (NSABP) study of tamoxifen and raloxifene (STAR) directly compared the two drugs in 19,747 healthy postmenopausal women at an increased risk for developing breast cancer.  Only healthy women who were postmenopausal, at least 35 years of age, and who had a 5-year Gail model-predicted breast cancer risk of at least 1.66% were eligible (see sidebar).  Women were enrolled between July 1999 and November 2004 and were randomized to receive either tamoxifen or raloxifene for 5 years.  The primary endpoint of the trial was incidence of invasive breast cancer.  The secondary endpoints included incidence of noninvasive breast cancer, endometrial and other cancers, and vascular-related events.

In the updated report, there was a statistically significant difference between the treatment groups for the incidence of invasive breast cancer.  The incidence of invasive breast cancer was significantly higher for women receiving raloxifene compared to women receiving tamoxifen.  There was no difference between the treatment groups for the incidence of noninvasive breast cancer.  The incidence of invasive uterine cancer was significantly lower for women receiving raloxifene compared to women receiving tamoxifen.  The incidence of pulmonary embolism and deep-vein thrombosis were significantly elevated in women receiving tamoxifen compared to women receiving raloxifene.  The rate of cataract development and cataract surgery was much lower in women receiving raloxifene compared to women receiving tamoxifen.  At 81 months of follow-up, the number of deaths observed in the two groups was similar.

The study investigators reported that both raloxifene and tamoxifen are good preventative choices for postmenopausal women with elevated risk for breast cancer.  But clinicians and patients should be conservative in interpreting the data and applying them to clinical practice.  The optimal duration of how many years that healthy women should be on either drugs is unknown.  The trial did not include a placebo group and did not enroll premenopausal women.  The trial lacked specificity in identifying a population of women who are truly at high risk for breast cancer, and the Gail model has not been validated for all ethnicities.  Furthermore, the trial has not demonstrated evidence of benefit from using these drugs beyond 7 years.  A much longer follow up of any prevention study is necessary to prove that the benefits outweigh the risks and that these drugs are truly beneficial in protecting healthy postmenopausal women against getting breast cancer.  Without a conservative approach, thousands of women who will never develop breast cancer will be exposed to potent drugs with demonstrated and potentially serious side effects.  

Click here for access to the original journal article.