Lectures and seminars PhD student seminar: Mattias Hammarström
Title: Tamoxifen and Endoxifen in Healthy Women: Dose, Exposure, Tolerability and Mammographic Breast Density
About the seminar
Breast cancer prevention with tamoxifen is effective, but treatment-related side effects may affect treatment acceptance and limit its clinical use.
This thesis investigates the effects of tamoxifen dose and its most potent metabolite, endoxifen, on treatment tolerability, adherence, and mammographic breast density (MBD), with the aim of improving the understanding of preventive endocrine therapy.
The thesis comprises four studies based on the KARISMA Tamoxifen and KARISMA Endoxifen clinical trials. Study I examined the association between tamoxifen dose and treatment-related symptoms. Study II investigated the relationship between endoxifen plasma concentrations and changes in MBD. Study III examined early non-adherence to tamoxifen and its association with adverse events. Study IV evaluated whether oral (Z)-endoxifen at two dose levels (1 and 2 mg) reduced MBD compared with placebo, while also assessing its tolerability and safety.
Overall, the findings demonstrate relationships between tamoxifen dose, treatment-related symptoms, adherence, endoxifen exposure, and MBD response. These results may contribute to more individualised approaches to breast cancer prevention by improving our understanding of dose–tolerability relationships, factors associated with treatment adherence, and interindividual differences in endoxifen exposure and response, while also exploring endoxifen as a potential preventive agent.