The role of HER2 pathway in vulvar paget's disease

Vulvar Paget's disease (VPD) is an orphan neoaplasm accounting 1-2 % of vulvar malignancies. Advanced VPD is currently laking effective treatment options. Since HER2 is overexpressed in 30-40 % of VPD cases, this scoping review explores its prognostic significance and the effectiveness of HER2-targeted therapies.

A literature review was conducted using the PubMed and Scopus databases. The search was restricted to articles in English and human studies, incorporating the terms "extramammary Paget disease", "vulva", "HER2", "anti-Her2 therapy" and "trastuzumab". Two reviewers screened abstracts and full-text article while recording relevant data.

Seventeen small retrospective studies on HER2 expression in VPD were evaluated. All studies assessed HER2 using IHC, while only 9 studies also employed FISH to detect gene amplification. A total of 270 patients are reported, of which 121 patients (45 %) had a 3 + or 2 + score. HER2/neu amplification was reported in 40 % of invasive tumours vs 17.5 % of non-invasive tumor. Eleven case-reports and series suggested a possible benefit of HER2-targeted therapies. To be mentioned, 4 articles reported trastuzumab combined with chemotherapy as the first-line treatment option, while trastuzumab monotherapy resulted in excellent objective response in two case reports.

Although HER2 expression in VPD represents a potential therapeutic target, current evidence is largely derived from case reports and lacks substantial clinical trial data. There is an urgent need for targeted clinical trials and expanded genomic profiling to enhance understanding of the underlying molecular mechanisms and optimize treatment strategies.