Tamoxifen Dose De-Escalation: An Effective Strategy for Reducing Adverse Effects?

Abstract

Tamoxifen, a cornerstone in the adjuvant treatment of estrogen receptor-positive breast cancer, significantly reduces breast cancer recurrence and breast cancer mortality; however, its standard adjuvant dose of 20 mg daily presents challenges due to a broad spectrum of adverse effects, contributing to high discontinuation rates. Dose reductions of tamoxifen might be an option to reduce treatment-related toxicity, but large randomized controlled trials investigating the tolerability and, more importantly, efficacy of low-dose tamoxifen in the adjuvant setting are lacking. We conducted an extensive literature search to explore evidence on the tolerability and clinical efficacy of reduced doses of tamoxifen. In this review, we discuss two important topics regarding low-dose tamoxifen: (1) the incidence of adverse effects and quality of life among women using low-dose tamoxifen; and (2) the clinical efficacy of low-dose tamoxifen examined in the preventive setting and evaluated through the measurement of several efficacy derivatives. Moreover, practical tools for tamoxifen dose reductions in the adjuvant setting are provided and further research to establish optimal dosing strategies for individual patients are discussed.

Fig. 1

Article selection; articles found by systematic search to 1 December 2023

Fig. 2

Practical advice for patients receiving treatment. Patients with ER-positive breast cancer who were treated with adjuvant tamoxifen reached steady-state levels of endoxifen after 3 months of treatment. From then on, the endoxifen concentration should be measured at least once. When a patient does not experience (bothersome) adverse effects, the standard dose of tamoxifen 20 mg can be continued if the endoxifen concentration is ≥16 nM. In case a patient experiences bothersome adverse effects, for some patients tamoxifen dose reduction can be considered using the conservative endoxifen threshold of 16 nM. AI aromatase inhibitor, ER+ estrogen receptor-positive. Figure created with Biorender