Tamoxifen Breast Cancer Prevention Has Small Mortality Effect

SACRAMENTO, Calif., July 24 -- As a breast cancer preventive agent, tamoxifen has little effect on mortality for most women, according to researchers here.

Tamoxifen is approved for breast cancer prevention if a woman has a five-year cancer risk of at least 1.67%, but life expectancy does not actually improve until the five-year risk is greater than 3%, according to Joy Melnikow, M.D., of the University of California at Davis.

Moreover, Dr. Melnikow and colleagues concluded, based on the average wholesale price of Nolvadex in the U.S. -- ,212 a year -- the drug is astonishingly costly, reaching ,335,690 per year of life saved at the 1.67% risk level.

By contrast, at Canadian Internet pharmacy prices -- averaging for a year's supply -- the cost per year of life saved at the 1.67% risk level would be ,780, Dr. Melnikow and colleagues reported in the Sept. 1 issue of the journal Cancer, a study that appeared online today.

"We found that for women at the lower end of the high-risk range for developing breast cancer, there is a very small likelihood that taking tamoxifen will reduce mortality," Dr. Melnikow said in a statement.

Using computer modeling and data derived from clinical trials and cancer surveillance databases, the researchers found that for women with a uterus and a 1.67% five-year breast cancer risk, taking tamoxifen results in a mean life expectancy increase of only 1.6 days.

While the drug does prevent breast cancer -- the risk is reduced by about 38% according to an analysis of all tamoxifen trials -- it has been shown to increase venous thromoboembolism, endometrial cancer, and cataracts requiring surgery. Those side effects combine to reduce the benefit in women near the 1.67% risk level, the researchers said.

Women taking tamoxifen are more likely to develop estrogen-receptor (ER) negative tumors, which have a worse prognosis than ER-positive cancers. When that is taken into consideration, Dr. Melnikow and colleagues found, tamoxifen actually appears to reduce survival until the five-year breast cancer risk is at least 2.1%.

A survival benefit isn't seen until the five-year risk is greater than 3%, the researchers said.

"This would support revising the current recommended risk threshold for physicians to counsel women about tamoxifen." Dr. Melnikow said.

The picture is better in women with a hysterectomy, the researchers reported, since the tamoxifen-induced risk of endometrial cancer is absent. For women without a uterus and a five-year risk of 1.67%, the mean life expectancy was increased by 26.7 days, and the cost per year of life saved was .778.

The findings "are highly sensitive to the price" of tamoxifen, the researchers noted. However, "regardless of the price of tamoxifen, the projected benefits of tamoxifen for women at or near the threshold risk for breast cancer (1.67%) are very small or nonexistent," they concluded.

The result is consistent with previously published models, which found that a five-year breast cancer risk of 3% to 4% is usually needed before tamoxifen produces improved life expectancy, Dr. Melnikow and colleagues said.