Endometrial Cancer

Introduction and Definition: Endometrial carcinoma, also referred to as endometrial cancer (EC), is a malignant tumor that arises from the epithelial lining of the uterus, known as the endometrium. EC is the most prevalent cancer of the female genital tract in developed countries, and its growing incidence driven by various risk factors is emerging as a significant public health concern. EC’s precise etiology is uncertain, although known risk factors are correlated with estrogen-progesterone imbalances. Due to high morbidity and mortality associated with EC, reviewing recent research on its etiology, risk factors, and future directions is critical. Body: ECs are classified as estrogen-dependent (type I) or estrogen independent otherwise (type II). Type 1 ECs are low-grade, endometrioid tumours often detected early and associated with better prognoses. Type II ECs exhibit non-endometroid histology, including carcinosarcomas, serous carcinomas, clear cell carcinomas, and other molecularly distinct tumours. Classification systems are evolving with new research to incorporate molecular, histological, and clinical factors, enhancing diagnosis and treatment protocols. Major risk factors and treatments emphasize the critical role of estrogen signalling, such that estrogen receptor α (ER) acts as an oncogenic signal. Genomic and nongenomic estrogen signalling pathways both contribute to the development of EC. Type I and type II ECs exhibit distinct risk factors, although both are associated with estrogen-progesterone imbalances. Type I EC risk factors include diabetes, obesity, early-onset menarche, and late-onset menopause, all of which result in prolonged exposure to unopposed estrogen. Type II ECs are less understood, but specific mutations involving TP53, and BRCA1/2 genes are implicated in its risk. The standard approach is often primary debulking surgery (PDS); however, neoadjuvant chemotherapy (NACT) is explored if the disease is deemed surgically unresectable. Ongoing clinical trials are exploring optimal treatment strategies. Germline mutations in the Breast Cancer gene 1/2 (BRCA1/2) are suggested to increase EC risk, although further studies are required to determine if EC is a BRCA1/2-associated disease. Current research suggests BRCA1/2, specifically BRCA1 mutation carriers have increased risk for EC, particularly in those with serous-like histology and TP53 mutations. Specified research can permit targeted treatments from a genetic and oncologic perspective.