GRACE-trial: a randomised active-controlled trial for vulvovaginal atrophy in patients with breast cancer on endocrine therapy – study protocol

INTRODUCTION: Breast cancer is the most common cancer type in women worldwide. Due to hormone receptor positivity in the majority of the breast cancer tumours is endocrine therapy a crucial part in the treatment landscape of breast cancer. Endocrine therapy consists of the use of selective oestrogen-receptor modulators or aromatase inhibitors. These medicines generate a hypoestrogenic environment by reducing circulating oestrogen or by altering the effect of oestrogen on tissue cells by receptor blockade. As a common side effect, vulvovaginal atrophy occurs in the majority of patients with breast cancer using endocrine therapy. Vulvovaginal atrophy has a significant impact on physical and psychological well-being due to negative influence on quality-of-life, self-esteem and sexuality. As a consequence, adherence to endocrine therapy for the standard duration of 5–10 years is challenging, resulting in higher rates of therapy interruption, leading to poorer prognosis with shorter distant disease-free survival. The standard treatment for vulvovaginal atrophy in postmenopausal women is based on the use of local hormonal treatment. However, when a patient has a history of breast cancer, delay of treatment and undertreatment are ubiquitous. METHODS AND ANALYSIS: In this first ever prospective randomised trial patients with breast cancer on endocrine therapy with vulvovaginal atrophy will be treated with the available local treatment modalities with a 1:1:1:1 randomisation: oestrogen, dehydroepiandrosterone, moisturisers and a co-treatment of oestrogen and probiotics. Patient-reported outcomes measurements will be implemented to investigate the efficacy of the implemented treatments. Safety of the treatments will be evaluated by assessing systemic sex hormones concentrations. ETHICS AND DISSEMINATION: This study was approved by the Ethical Committee of Ghent University Hospital and by the Federal Agency for Medicines and Health Products. Results will be published in peer-reviewed journals and released in international conferences. TRIAL REGISTRATION NUMBER: 2021-001921-31.