Endometrial cancer: molecular classification and future treatments

Abstract

The treatment for endometrial cancer is rapidly evolving with the development of molecular analysis and novel strategies. Surgical resection, cytotoxic chemotherapy, endocrine or hormonal treatment, and radiation have been the staples of treatment for decades. However, precision based approaches for tumours are rapidly becoming a part of these strategies. Biomarker driven treatments are now a part of primary and recurrent treatment algorithms. This review aims to describe the current state of molecular analysis and treatment for endometrial cancer as well as to elucidate potential approaches for the near future.

Emerging Advances in Endometrial Cancer: Integration of Molecular Classification into Staging for Enhanced Prognostic Accuracy and Implications for Racial Disparities

“…These findings guide stratification of patients as low, intermediate, or high-risk for extra-uterine disease or recurrence and in need of adjuvant therapies after surgery. Generally, low risk patients are recommended for observation alone while those with higher risk due to advanced FIGO stage, aggressive histology, high grade, or deep myometrial invasion are advised for more aggressive adjuvant therapies [ 22 ]. The importance of adjuvant therapy such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined chemotherapy and radiotherapy in higher risk patients have been evaluated in several studies such as GOG 258 and PORTEC-3 and have established current standards of care based on histopathology and stage [ 23 , 24 ].…”

“…However, over the past decade, several groups have demonstrated that certain molecular subtypes of endometrial cancer can have a substantial impact on prognosis, recurrence, and survival outcomes in various cohorts of patients [ 25 ]. Molecular analysis and molecular-driven treatments have become an important aspect of patient-directed care in endometrial cancer, offering the potential for more personalized therapeutic strategies [ 22 , 26 , 27 , 28 , 29 , 30 ]. In addition, clinical trials investigating more personalized therapeutic strategies or different systemic treatment options in patients with advanced/recurrent endometrial carcinoma based on molecular profiles are in progress.…”

“…Microsatellite instability hypermutated (MSI-H) tumors exhibit high levels of microsatellite instability due to defects in mismatch repair (MMR) genes [ 30 , 35 ]. The term MSI-H tumors, referring to the phenotype, is often interchanged with the term MMR deficient, referring to the genotype [ 22 ]. This group composes approximately 30% of all endometrial cancers and 13–30% of recurrent/metastatic endometrial cancers [ 42 , 43 ].…”

“…Of the four TGCA molecular subtypes, the most common is the copy-number low subtype [ 22 ]. Its molecular characteristics include a relatively low mutational burden, characterized by fewer changes in the copy number variations throughout the genome and fewer deletions or duplications of large sections of DNA [ 22 , 47 ]. This results in more genome stability compared to the “copy-number high” subtype, which exhibits a higher number of these alterations.…”

“…The endometrioid histologic type comprises the majority of the copy-number low category [ 22 ]. Copy-number low endometrial cancers often present at an earlier stage and have a favorable prognosis with a lower risk of recurrence [ 22 , 47 ].…”