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

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.

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.

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.