Study Shows Tamoxifen Has Little Impact on Mortality

Tamoxifen as a breast cancer prevention drug has little impact on overall mortality rates for most "high-risk" women, according to a new study. For women with the minimum 1.67% 5-year breast cancer risk who are eligible to take tamoxifen, there were no mortality rate benefits to taking the drug. Scheduled for publication in the September 1, 2006, issue of CANCER, the study reveals that life expectancy improved when women were at the higher end of breast cancer risk—ie, greater than 3%. Moreover, the high price of tamoxifen in the United States resulted in extraordinarily high cost per life year saved, further reducing tamoxifen's utility as a cancer prevention drug in this country.

Tamoxifen Refresher

Tamoxifen is a selective estrogen-receptor (ER)-modulating drug used to treat ER-positive breast cancers. It has also been shown to prevent breast cancer in high-risk women. The landmark chemoprevention study for tamoxifen found that among women who meet the minimum eligibility criteria for "high risk" (ie, a 5-year risk of breast cancer of at least 1.67%), tamoxifen use resulted in a 49% reduction in (ER-positive) breast cancers. However, its effect on survival has not been studied. The drug is associated with significant adverse effects, such as cataracts, deep-vein thromboses, uterine cancer, and strokes. Women on tamoxifen who do develop breast cancer will more likely develop ER-negative breast cancers, which have a worse prognosis.

Dr. Joy Melnikow, of the department of family and community medicine at the University of California, Davis, and colleagues used a modeling strategy to investigate whether tamoxifen was an effective drug for breast cancer risk reduction. The researchers found that there was no mortality benefit "for women at the lower end of the high-risk range for breast cancer." However, life expectancy benefit was seen for women who already had a hysterectomy, and thereby eliminated the drug's risk of endometrial cancer. When taking into account ER-negative breast cancers, an approach that has not been investigated before, mortality rates actually increased slightly until 5-year risk reached more than 2%.

Calculated Costs

For women at the threshold 5-year risk of 1.67%, and with the drug cost at $1,212 per year (average wholesale price) in the United States, the authors calculated a cost of $1,335,690 per year of life saved, an extraordinarily high cost-to-effectiveness ratio. In contrast, in the Canadian pharmaceutical market, the authors calculated $123,780 per year of life saved. Even at Canadian drug prices, tamoxifen both improved life expectancy and saved costs only when a woman's 5-year risk was at least 4%.

This study finds that it would take a breast cancer risk greater than 3%, particularly in women who have not had a hysterectomy, to see potential benefit from tamoxifen. "The projected benefits of tamoxifen for women at or near the threshold risk for breast cancer (1.67%) are very small or nonexistent" conclude the authors of the study, and would help only a "relatively small proportion of women." Moreover, the drug price's impact on cost-effectiveness, according to the investigators, "illustrates the potential effect of negotiating pharmaceutical prices at a national level."