In 1998, the National Surgical Adjuvant Breast and Bowel Project reported the results of its Breast Cancer Prevention Trial (BCPT) in which tamoxifen was assessed for its benefits with regard to prevention among women with higher than average breast cancer risk (1).  Participants in the BCPT were required to have the same risk of developing breast cancer as an average 60-year old woman (1,2). In this study tamoxifen decreased the risk of invasive breast cancer by close to 50% in such women, on the basis of these findings, tamoxifen became the first agent approved by the Food and Drug Administration for the chemoprevention of breast cancer (3). In fact, subset analyses from the BCPT suggested that tamoxifen may be especially beneficial for women with atypical ductal hyperplasia, lobular carcinoma in situ, those with 2 or more first degree relatives diagnosed with breast cancer, or women with a 5-fold increased risk of developing breast cancer (1). These subsets of women have risks for breast cancer 4 to 7 times greater than women in the general population. 

At the Herbert Irving Comprehensive Cancer Center of New York- Presbyterian Hospital, Dr. Dawn L. Hershman and colleagues used computer simulations to estimate the effects of tamoxifen chemoprevention on survival, quality-adjusted survival, and health care costs in hypothetical cohorts of women similar to those in the high-risk subgroups who participated in the BCPT (4). For each of the subgroups analyzed, the computer model predict a greater survival and quality-adjusted survival benefit than for the BCPT cohort overall. The survival benefit was greatest for women with a history of atypical hyperplasia who started tamoxifen at age 35 and had a benefit of more than 7 months. Women with a 5-fold increased risk of developing breast cancer and those with lobular carcinoma in situ also benefited from nearly similar survival rates. In these subgroups, tamoxifen use resulted in similar, but smaller quality-adjusted survival benefits. The cost per life-year saved and cost per quality-adjusted life-year saved were also markedly lower for the study participants as a whole in each of the subgroups analyzed. 

Few physicians are prescribing tamoxifen for the prevention of breast cancer, and the reasons are unclear. Perhaps it is because tamoxifen chemoprevention is unlikely to give a significant survival benefit to the majority of women.  Using decision analysis and computer modeling for subgroups of women who are at the highest risk for breast cancer, Dr. Hershman and her colleagues have shown substantial gains in both survival and quality-adjusted survival when tamoxifen is used as a chemopreventive agent, especially in young women who are at very high risk for developing breast cancer. The findings support targeting chemoprevention to those women with the highest risk of developing breast cancer and placing them on the STAR Chemoprevention Trial.

Editor’s note: 

Dawn L. Hershman, M.D., M.P.H. is Assistant Professor of Medicine at the Herbert Irving Comprehensive Cancer Center of New York- Presbyterian Hospital.

1. Fisher, B., Costantino, J.P., Wickerham, D.L., Redmond, C.K., Kavanah, M., Cronin. W.M., Vogel, V., Robidoux, A., Dimitrov, N., Atkins, J., Daly, M., Wieand, S., Tan-Chiu, E., Ford, L., and Wolmark, N. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998, 90(18):1371-88.

2. Gail, M.H., Brinton, L.A., Byar, D.P., Corle, D.K., Green, S.B., Schairer, C., and Mulvihill, J.J. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989, 81(24):1879-86. 

3. Fisher, B. National surgical adjuvant breast and bowel project breast cancer prevention trial: a relective commentary. J Clin Oncol. 1999, 17:1632-39.

4. Hershman, D., Sundararajan, V., Jacobson, J., Neugut, A., and Grann, V. Benefits of tamoxifen for the prevention of breast cancer among women with varying risks: a decision analysis. J Clin Oncol. 2002; 20-9-16.