The POWER Trial: Personalised Dose Optimisation With Adjuvant Tamoxifen Therapy in Breast cancER

Summary

In Sweden, approximately 7000 women are diagnosed with hormone-sensitive breast cancer annually. According to international and national guidelines, most of these women are recommended anti-hormonal therapy for five to ten years to improve prognosis. Tamoxifen, one of the most widely used anti-hormonal agents globally, reduces the risk of recurrence by 40% and breast cancer mortality by 30%.

Tamoxifen is a pro-drug that undergoes hepatic metabolism to form endoxifen and other active metabolites. Variability in metabolic capacity affects therapeutic efficacy: poor metabolisers produce insufficient endoxifen and other active metabolites, risking therapeutic failure, while ultrarapid metabolisers generate excessive amounts, leading to intolerable adverse effects. Today, 30-50% of patients discontinue treatment prematurely due to severe side effects, resulting in suboptimal outcomes.

Currently, tamoxifen is uniformly prescribed at a daily dose of 20 mg, and so far, no clinical trials have tested whether individualised dosing could enhance adherence and improve survival outcomes. The primary objective is to evaluate whether individualised tamoxifen dosing reduces discontinuation rates and enhances patient outcomes in breast cancer treatment.

Conditions

• Breast Cancer
• Adjuvant Drug Therapy

Interventions

DRUG

Individual dose of tamoxifen

Each subject starts their treatment with the standard dose 20 mg tamoxifen daily by oral intake. During visits 2 (3 months), 3 (six months) and 4 (twelve months), the investigator will either let the patient remain on 20 mg tamoxifen or individualise the dose. The investigator may change the daily tamoxifen from 20 mg per day to: a halved dose to 10 mg, or a doubled dose to 40 mg. The recommendation for oral intake of tablet(s) tamoxifen for a daily dose of 10, 20 or 40 mg is accordingly: for 10 mg: one tablet (20 mg) every two days for 20 mg: one tablet (20 mg) every day for 40 mg: two tablets (20 mg) every day.

DRUG

Standard adjuvant therapy of tamoxifen

The global standard dose for everyone is 20 mg orally once per day. Each subject undergoes treatment with the standard dose 20 mg daily by oral intake of one tablet, with no possibility of dose adjustment during the trial.

Sponsors & Collaborators

• Swedish Cancer Society

  collaborator OTHER

• Region Stockholm

  collaborator OTHER_GOV

• The Swedish Breast Cancer Association

  collaborator UNKNOWN

• The Sjöberg Foundation

  collaborator UNKNOWN

• The Cancer Research Foundations of Radiumhemmet

  collaborator UNKNOWN

• Karolinska Institutet

  lead OTHER

Principal Investigators

• Marike Gabrielson, PhD · Karolinska Institutet

• Jenny Bergkvist, MD, PhD · Karolinska Institutet

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-03-31

Primary Completion

2036-08-31

Completion

2036-08-31

Countries

• Sweden

Study Locations