{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:59:55Z","timestamp":1773341995441,"version":"3.50.1"},"reference-count":22,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"unspecified","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011851","name":"Kom op tegen Kanker","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100011851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2023,3,27]]},"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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\u201310 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>2021-001921-31.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2022-068053","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T11:22:33Z","timestamp":1681212153000},"page":"e068053","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["GRACE-trial: a randomised active-controlled trial for vulvovaginal atrophy in patients with breast cancer on endocrine therapy \u2013 study protocol"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2213-163X","authenticated-orcid":false,"given":"Glenn","family":"Vergauwen","sequence":"first","affiliation":[{"name":"Cancer Research Institute Ghent, Ghent University, Gent, Belgium"},{"name":"Department of Obstetrics - Gynaecology, University Hospital Ghent, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piet","family":"Cools","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sciences, Ghent University, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannelore","family":"Denys","sequence":"additional","affiliation":[{"name":"Cancer Research Institute Ghent, Ghent University, Gent, Belgium"},{"name":"Department of Medical Oncology, University Hospital Ghent, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Fiers","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, University Hospital Ghent, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen","family":"Van de Vijver","sequence":"additional","affiliation":[{"name":"Cancer Research Institute Ghent, Ghent University, Gent, Belgium"},{"name":"Department of Pathology, University Hospital Ghent, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liv","family":"Veldeman","sequence":"additional","affiliation":[{"name":"Cancer Research Institute Ghent, Ghent University, Gent, Belgium"},{"name":"Department of Radiation Oncology, University Hospital Ghent, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Verstraelen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics - Gynaecology, University Hospital Ghent, Gent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"2025120618171649000_13.4.e068053.1","unstructured":"International Agency for Research on Cancer . 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