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 percent 5-year breast cancer risk who are eligible to take tamoxifen, there were no mortality rate benefits to taking tamoxifen. Published in the September 1, 2006 issue of CANCER (http://www.interscience.wiley.com/cancer-newsroom), a peer-reviewed journal of the American Cancer Society, the study reveals that life expectancy improved when women were at the higher end of breast cancer risk – i.e., greater than 3 percent. Moreover, the high price of tamoxifen in the U.S. resulted in extraordinarily high cost per life year saved, further reducing tamoxifen's utility as a cancer prevention drug in the U.S.
Tamoxifen is a selective estrogen receptor (ER) modulating drug used to treat estrogen-receptor 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 FDA eligibility criteria for "high risk" (i.e., a 5-year risk of breast cancer of at least 1.67 percent) tamoxifen use resulted in a 49 percent 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.
Joy Melnikow, M.D., M.P.H. 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 percent.
For women at the threshold 5-year risk of 1.67%, and with the drug cost at $1212 per year (Average Wholesale Price) in the U.S., the author 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 percent.
This study finds that it would take a breast cancer risk greater than 3 percent, 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 percent) are very small or non-existent" 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."
Article: "Chemoprevention: Drug Pricing and Mortality: The Case of Tamoxifen," Joy Melnikow, Christina Kuenneth, L. Jay Helms, Amber Barnato, Miriam Kuppermann, Stephen Birch, James Nuovo, CANCER; Published Online: July 24, 2006 (DOI: 10.1002/cncr.22075); Print Issue Date: September 1, 2006.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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