Modeling the effect of tamoxifen chemoprevention on long-term mortality in white women at high risk of breast cancer

Tamoxifen has long been studied as a drug to treat breast cancer and now for its preventive effect. Intermediate results from studies on the preventive effect of tamoxifen vs. placebo endorsed tamoxifen's efficacy after a short follow-up. Effect of tamoxifen on long-term survival was simulated in women at a high risk of breast cancer. The model allows for tamoxifen effect on breast cancer according to estrogen receptor status, endometrial cancer, and pulmonary embolism. A virtual cohort of 200 000 white women was split into two treatment arms (placebo vs. tamoxifen), two age groups (35-49 and 50-74), and followed-up for 20 years. Incidence rates stemmed from the National Surgical Adjuvant Breast and bowel Project-P1, or the chemoprevention trials overview by Cuzick et al., and relative survival probabilities from surveillance, epidemiology, and end results. Six hypotheses of tamoxifen effects and their variations along time were considered. In the National Surgical Adjuvant Breast and Bowel Project-based results, women aged 35-49 took advantage of tamoxifen whatever the follow-up duration and hypothesis, except the one of only side effects remaining 15 years after treatment withdrawal. In the overview-based results, the advantage existed only when effect on pulmonary embolism stopped. Women aged 50-74 experienced underwent tamoxifen side effects that outweighed advantages whatever the follow-up duration and hypothesis, except the one of only beneficial remaining effect 15 years after treatment withdrawal. Overall, the slight positive effect of tamoxifen on long-term mortality should be cautiously interpreted for young women. In women aged over 50 years, however, tamoxifen chemoprevention could not be recommended.