The WinPro trial: window-of-opportunity study of endocrine therapy with micronised progesterone in ER-positive breast cancer

Progesterone can inhibit tumoural proliferation in oestrogen receptor positive (ER+) breast cancer. The WinPro trial (Australian New Zealand Trials Clinical Trials Registry number: ACTRN12618000928213, date of registration 01/06/2018) was a randomised, multi-centre, phase 2, window-of-opportunity trial evaluating micronised progesterone (MP) in post-menopausal women with early-stage, ER+, progesterone receptor (PR) positive, HER2- breast cancer. Patients were randomised to letrozole, letrozole and MP, or tamoxifen and MP for 14 days preoperatively. The primary endpoint was the percent proportional reduction in Ki67 (‘Ki67 suppression’) between the two letrozole groups in the per protocol population. From February 2018 to June 2024, 244 patients were enrolled. 189 patients completed per protocol: letrozole ( n = 66, 34.9%), letrozole + MP ( n = 64, 33.9%), and tamoxifen + MP ( n = 59, 31.2%). There was no difference in Ki67 suppression between letrozole (88.2%) versus letrozole + MP (89.2%) ( p = 0.39). Ki67 suppression appeared lower with tamoxifen + MP (61.5%). Hot flushes appeared less frequent with letrozole + MP (13.3%) versus letrozole (22.4%) or tamoxifen + MP (20.5%).