Estimation of tamoxifen's efficacy for preventing the formation and growthof breast tumors

Background: Several randomized clinical trials have tested the hypothesis t hat tamoxifen is effective in preventing breast cancer. The largest such tr ial, the National Surgical Adjuvant Breast and Bowel Project's Breast Cance r Prevention Trial (BCPT), reported a 49% reduction in risk of invasive bre ast cancer for the tamoxifen group. However, it is unclear whether the effe ct of tamoxifen in this trial was mainly due to prevention of newly forming tumors or to treatment of occult disease. Methods: We used various tumor g rowth models (i.e., exponential and Gompertzian [growth limited by tumor si ze]) and a computer simulation to approximate the percentage of detected tu mors that were initiated after study entry. Maximum likelihood techniques w ere then used to estimate separately the efficacy of tamoxifen in treating occult disease and in preventing the formation and growth of new tumors, Re sults: Under the assumptions of most of the growth models, the trial was su fficiently long for substantial numbers of new tumors to form, grow, and be detected during the trial. With the Gompertzian model and all available in cidence data from the BCPT, it was estimated that 60% (95% confidence inter val [CI] = 40%-80%) fewer new tumors were detected in the tamoxifen group t han in the placebo group. Likewise, 35% (95% CI = 6%-63%) fewer occult tumo rs were detected in the tamoxifen group. With this model, the estimated inc idence rate of invasive breast cancer among women in the placebo group of t he BCPT was 7.7 (95% CI = 6.6-8.9) per 1000 women per year. Similar results were obtained with three exponential tumor growth models. Conclusions: The se results support the concept that tamoxifen reduced cancer incidence in t he BCPT through both treatment of occult disease and prevention of new tumo r formation and growth. However, data from prevention trials may never be s ufficient to completely distinguish prevention of new tumor formation from treatment of occult disease.