Most women at high risk for breast cancer do not increase their life expectancy by taking the drug tamoxifen, according to a new analysis by researchers from UC Davis, UCSF, the University of Pittsburgh and McMaster University in Ontario, Canada.

In addition, the researchers showed that tamoxifen is an extraordinarily expensive cancer-prevention strategy, costing as much as $1.3 million per year of life saved. The study will be published in the Sept. 1 issue of the American Cancer Society's journal Cancer.

"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," said Joy Melnikow, professor of family and community medicine at UC Davis School of Medicine and Medical Center and lead author of the study. "This would support revising the current recommended risk threshold for physicians to counsel women about tamoxifen."

Tamoxifen was approved by the U.S. Food and Drug Administration in 1998 for breast cancer prevention in women who have at least a 1.67-percent chance of developing the disease over the next five years. Such women are considered at high risk for breast cancer. Groups such as the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care recommend that physicians counsel women above this threshold about the benefits and risks of tamoxifen as a means of preventing the disease.

Tamoxifen is a selective estrogen receptor-modulating drug used to treat estrogen receptor-positive breast cancers. In addition, it has been shown to reduce the incidence of invasive breast cancer among high-risk women by up to 49 percent.

However, tamoxifen is associated with significant adverse effects, including cataracts requiring surgery, deep vein thromboses, endometrial cancer and stroke. Women taking tamoxifen, if they do develop breast cancer, are also more likely to develop an estrogen receptor-negative tumor, which has a worse prognosis. (Cancers prevented by tamoxifen are mostly estrogen receptor-positive).

In the new study, Melnikow and her colleagues calculate that tamoxifen can be expected to extend life expectancy only when a woman's five-year risk of developing breast cancer reaches 3 percent or more. This is especially true for women who have not had a hysterectomy, and therefore face the risk of endometrial cancer related to tamoxifen use.

Cost-effectiveness was also calculated in the study. For women at the 1.67-percent risk level, taking tamoxifen to stave off breast cancer came to $1.3 million per year of life saved based on the U.S. price of the drug -- a prohibitively expensive cancer-prevention strategy. Melnikow and her co-authors note, however, that the cost-effectiveness equation could be improved if pharmaceutical prices were negotiated at a national level. At Canadian prices, for example, the researchers showed that taking tamoxifen to prevent breast cancer comes to $123,780 per year of life saved for women at the 1.67-percent risk level.

In comparison, annual flu shots cost about $980 per year of life saved for patients ages 65 and older; colonoscopy every 10 years costs about $11,000 per year of life saved for people 50 and older; and annual mammography costs about $58,000 per year of life saved for women ages 40 to 80.

To arrive at their findings, Melnikow and her colleagues used a complex mathematical model based on a hypothetical group of 50-year-old women.

Melnikow specializes in research to better understand women's health-care preferences and how women make health-care decisions. In a study published in the journal Cancer last year, she reported that among women with a five-year breast cancer risk of 1.67 percent or higher, fewer than one in five were inclined to take tamoxifen to prevent the disease. Concern about potential side effects was the primary reason.