Whilst the majority of Endometrial Cancers (ECs) are common Type 1 endometrioid cancers, accounting for 75-80% of cases, with a good prognosis, Type 2 ECs include high-grade, clinically aggressive histologies, with poor response rates to hormonal therapies. Serous endometrial carcinoma is the second most common type, accounting for ~10 percent of cases, most with a p53 abnormality and a lesser proportion with HER2 overexpression/amplification/mutation. Clear cell endometrial carcinoma accounts for <5 % of EC, with the most aggressive cases also having p53 mutations. Mixed histologies and undifferentiated ECs are also aggressive. Carcinosarcoma (ECS) is a rare, aggressive, biphasic carcinoma that accounts for <5 percent of ECs, 90% with p53 abnormalities. Endometrial stromal sarcomas (ESS) can be low-grade or high-grade, or undifferentiated or resemble ovarian sex cord tumors. Uterine leiomyosarcoma (uLMS) are epithelioid or myxoid in type. Adenosarcoma involves a benign epithelial component mixed with a malignant stromal element. Whilst there have been considerable improvements in death rates for all cancers combined over the last 20 years, these improvements have not been seen for most rare cancers (RC). In order to ensure that those diagnosed with RC have access to research and novel therapies, we designed the Walter and Eliza Hall Institute of Medical Research (WEHI) Stafford Fox Rare Cancer Program (SFRCP). The WEHI-SFRCP has streamlined ethics, governance, consenting processes, including remote consent at home anywhere in Australia, and data collection protocols to allow the analysis of data and tissue of any type of RC. We have interconnected clinical and laboratory RC Databases within BioGrid Australia using the online REDCap platform. We have extensive laboratory processes in place for processing of tumour and blood samples, including the generation of PBMCs, DNA, RNA, to generate NGS including WGS; patient-derived xenografts (PDX), organoids, cell lines and other derivatives. We have high grade serous endometrial cancer (33 cases, including 4 PDX with 3 pending); uLMS (32 cases, including 2 PDX with 3 pending); endometrial carcinosarcoma (13 cases, including 3 PDX, 1 pending); rare (other, adenosarcoma, STUMP). We perform NGS testing on cases, depending on tumour purity, including Whole Genome Sequencing from fresh tumour samples; characterize PDX according to current chemotherapy and relevant novel therapeutics; study rare endometrial subtypes in specific projects and also provide information back to patients to guide therapy in the clinic. By integrating data sets with endometrial projects of similar depth we will drive forward the study of rare endometrial cancer subtypes.

Citation Format: Clare L. Scott, Ratana Lim, Amandine Carmagnac, Cassandra Vandenberg, Gayanie Ratnayake, Genevieve Dall, Joshua Tram, Justin Bedo, Jocelyn Penington, Joep Vissers, Sean Grimmond, Matthew Wakefield, Anthony Papenfuss, Holly Barker. Building the infrastructure required to research novel therapies for 35% of women with endometrial cancer who have rare subtypes [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO026.