Clinical Epidemiology (Apr 2025)

Statin Therapy in Early Breast Cancer: The MASTER Trial; A Randomized Phase III, Placebo-Controlled Comparison of Standard (Neo)Adjuvant Therapy Plus Atorvastatin versus Standard (Neo)Adjuvant Therapy Plus Placebo

  • Borgquist S,
  • Jensen MB,
  • Bendorff CL,
  • Christiansen P,
  • Offersen BV,
  • Kodahl AR,
  • Ewertz M,
  • Jensen AB,
  • Ahern TP,
  • Cronin-Fenton D,
  • Ejlertsen B

Journal volume & issue
Vol. Volume 17
pp. 409 – 419

Abstract

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Signe Borgquist,1,2 Maj-Britt Jensen,3 Cecilie Linea Bendorff,1 Peer Christiansen,4 Birgitte Vrou Offersen,1 Annette Raskov Kodahl,5,6 Marianne Ewertz,6 Anders Bonde Jensen,1 Thomas P Ahern,1,7 Deirdre Cronin-Fenton,8 Bent Ejlertsen3 On behalf of the Danish Breast Cancer Group1Department of Oncology, Aarhus University Hospital/Aarhus University, Aarhus, Denmark; 2Division of Oncology, Clinical Sciences, Lund University, Lund, Sweden; 3Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 4Department of Plastic and Breast Surgery, Aarhus University Hospital/Aarhus University, Aarhus, Denmark; 5Department of Oncology, Odense University Hospital, Odense, Denmark; 6Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 7Department of Surgery, The Robert Larner, M.D. College of Medicine at The University of Vermont, Burlington, VT, USA; 8Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital/Aarhus University, Aarhus, DenmarkCorrespondence: Signe Borgquist, Department of Oncology, Aarhus University Hospital/Aarhus University, Palle Juul-Jensens Blvd 99, Aarhus N, 8200, Denmark, Email [email protected]: Statin use has been consistently associated with improved clinical outcomes (especially recurrence) in breast cancer in multiple observational studies backed by compelling preclinical evidence. The strength of this evidence warrants a clinical trial to test the efficacy of statin exposure on breast cancer recurrence.Patients and Methods: The double-blind, phase III, randomized, placebo-controlled MASTER (MAmmary cancer STatins in ER positive breast cancer) trial includes women diagnosed with early-stage, estrogen receptor-positive (ER+) breast cancer who are candidates for systemic (neo)adjuvant therapy. Enrolled patients are given standard (neo)adjuvant therapy and additionally randomized to either atorvastatin (80 mg/day) or placebo for two years. The trial’s primary outcome is invasive disease-free survival (IDFS), with a target accrual of 3360 patients in total to achieve 80% power (two-sided alpha=0.05) to detect a 25% reduction in the risk of an IDFS event comparing the statin and placebo arms. At 3-, 6-, 12-, and 24-month follow-up time points, patients will have blood drawn for biomarker studies, answer patient-reported outcome (PRO) questionnaires, and control for adverse events. Subsequently, patients will receive annual PRO-criteria for Adverse Events (CTCAE) questionnaires until the completion of their 10 years of follow-up. Secondary endpoints include additional clinical endpoints; pathological response (neo-adjuvant treated patients), recurrence-free survival, distant-recurrence-free interval, overall survival and cardiac death-free interval, co-morbidity, and health-related quality-of-life measured by PRO-CTCAE questionnaires during and beyond study medication. Translational endpoints are evaluated in collected blood- and tumor samples.Discussion: If a protective effect of statins on breast cancer recurrence is supported by evidence from the MASTER trial, then the indications for a safe, well-tolerated, and inexpensive treatment can be expanded towards improved clinical outcomes for breast cancer patients.Keywords: statin, breast cancer, recurrence, cholesterol, endocrine therapy, randomized trial

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