The researchers suggest from these findings that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention.
An accompanying commentary commends the researchers on the achievement of such long-term follow-up, especially with more than 74% of participants remaining masked to randomisation. It calculates a number needed to treat of only 22 women receiving tamoxifen for 5 years to prevent one case of breast cancer in the next 20 years. The commentary suggests the findings have clinical implications because many women could be spared the psychological and physical problems associated with a breast cancer diagnosis and related treatment. However, the slightly higher number of deaths from breast cancer in the tamoxifen group than in the placebo group (not significantly different), which persisted beyond 10 years' follow-up raises a series of questions. It postulates that the discordance between the effect of tamoxifen on breast cancer incidence and deaths from breast cancer could merely represent the effects of chance alone, or alternatively might indicate that tamoxifen mainly decreases the incidence of cancers with a very favourable prognosis, increases cancers with unfavourable outcomes, or both. How these alternative ideas are viewed will determine the effect of the IBIS-I update on breast cancer chemoprevention practice in the clinic.