Side effects of low-dose tamoxifen: results from a six-armed randomised controlled trial in healthy women

Br J Cancer. 2023 Jul;129(1):61-71. doi: 10.1038/s41416-023-02293-z. Epub 2023 May 6.

Abstract

Background: Adherence to adjuvant tamoxifen therapy is suboptimal, and acceptance of tamoxifen for primary prevention is poor. Published results indicate effect of low-dose tamoxifen therapy. Using questionnaire data from a randomised controlled trial, we describe side effects of standard and low-dose tamoxifen in healthy women.

Methods: In the KARISMA trial, 1440 healthy women were randomised to 6 months of daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. Participants completed a 48-item, five-graded Likert score symptom questionnaire at baseline and follow-up. Linear regression models were used to identify significant changes in severity levels across doses and by menopausal status.

Results: Out of 48 predefined symptoms, five were associated with tamoxifen exposure (hot flashes, night sweats, cold sweats, vaginal discharge and muscle cramps). When comparing these side effects in premenopausal women randomised to low doses (2.5, 5 mg) versus high doses (10, 20 mg), the mean change was 34% lower in the low-dose group. No dose-dependent difference was seen in postmenopausal women.

Conclusions: Symptoms related to tamoxifen therapy are influenced by menopausal status. Low-dose tamoxifen, in contrast to high-dose, was associated with less pronounced side effects, a finding restricted to premenopausal women. Our findings give new insights which may influence future dosing strategies of tamoxifen in both the adjuvant and preventive settings.

Trial registration: ClinicalTrials.gov ID: NCT03346200.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / adverse effects
  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / drug therapy
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Hot Flashes / chemically induced
  • Hot Flashes / drug therapy
  • Hot Flashes / prevention & control
  • Humans
  • Premenopause
  • Surveys and Questionnaires
  • Tamoxifen / therapeutic use

Substances

  • Tamoxifen
  • Antineoplastic Agents, Hormonal

Associated data

  • ClinicalTrials.gov/NCT03346200