Background: The aim of this study was to evaluate whether molecular classification prognosticates treatment response in women with endometrial cancers and endometrial intraepithelial neoplasia (EIN) treated with levonorgestrel intrauterine system (LNG-IUS). Methods: Patients treated with LNG-IUS for endometrial cancer or EIN from 2013 to 2018 were evaluated. Using immunohistochemistry and single gene sequencing of POLE, patients were classified into four groups as per the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE): POLE-mutated, mismatch repair-deficient (MMRd), p53 wild type (p53wt), and p53-abnormal (p53abn). Groups were assessed relative to the primary outcome of progression or receipt of definitive treatment. Results: Fifty-eight subjects with endometrioid endometrial cancer or EIN treated with LNG-IUS were included. Of these, 22 subjects (37.9%) had endometrial cancer and 36 subjects (62.1%) had EIN. Per the ProMisE algorithm, 44 patients (75.9%) were classified as p53wt, 6 (10.3%) as MMRd, 4 (6.9%) as p53abn, and 4 (6.9%) as POLE-mutated. Of the 58 patients, 11 (19.0%) progressed or opted for definitive therapy. Median time to progression or definitive therapy was 7.5 months, with p53abn tumors having the shortest time to progression or definitive therapy. Conclusions: Molecular classification of endometrial cancer and EIN prior to management with LNG-IUS is feasible and may predict patients at risk of progression.

As sex and gender are assigned at birth before gender identity development, many individuals experience feelings of discordance between their gender identity and their sex and gender assigned at birth. The transgender community has not been well understood by medical and mental health fields. As such, this marginalized and vulnerable community faces multiple barriers to receiving health maintenance and specialized care, both at the community and patient-specific level. Many transgender individuals undergo some form of transition to the gender that matches their gender identity. Transition efforts look different for each patient because gender and gender identity occur along a continuum. Transition may include social, hormonal, and/or surgical components. As providers are caring for transgender patients, it is imperative to understand where a patient is in their gender transition and how hormonal and/or surgical therapies affect their cancer risk and screening. The aim of this article is to describe appropriate cancer screening practices and important care considerations for the primary care physician and generalist gynecologist taking care of transgender individuals.