Uterine Cancer Overview^[condition] and NIH Women's Health Research

The most common type of uterine cancer is endometrial cancer, which begins with a thickening of the endometrium.¹ Because of this, uterine bleeding that occurs at unusual times, such as after menopause or between periods, can be an early sign of this type of cancer.² This generally makes it easier to diagnose endometrial cancer at an early stage. Despite this, the mortality rate for this type of cancer is rising in the United States; the American Cancer Society reports that the mortality rate for women with endometrial cancer increased by 1.5% per year between 2013 and 2022.³ Uterine sarcomas, which arise from either myometrial muscle or stroma, account for only a small proportion (2% to 5%) of uterine cancer cases.⁴

Endometrial cancer typically occurs after menopause, and women have an increased risk of this type of cancer if they have been receiving unopposed estrogen for hormone replacement therapy or if they have obesity, endometrial hyperplasia, or polycystic ovary syndrome.^{2 , 5} Women with a family history of endometrial cancer and certain other types of cancer, including ovarian cancer and colorectal cancer, also have a higher risk of endometrial cancer.² Taking the selective estrogen receptor modulator tamoxifen as a treatment for breast cancer has been associated with an increased risk of both endometrial cancer and uterine sarcomas.^{2 , 4 , 5}

Significant racial disparities have been reported in cases of uterine cancer; in a study supported by the National Cancer Institute (NCI), the authors noted that the rates of deaths among Black women from both uterine cancer overall and from nonendometrioid subtypes specifically are more than twice as high as the rates among other racial and ethnic groups.⁶ This discrepancy persisted regardless of the stage at which Black women received their cancer diagnosis. This represents one of the largest gaps in survival rates between Black and White people among cancers; it is second only to melanoma.⁷

Traditionally, endometrial cancer has been divided into two subtypes that are based on histomorphological characteristics. In 2013, The Cancer Genome Atlas (TCGA), a collaboration between NCI and the National Human Genome Research Institute, used integrated genomic data to identify four molecular subtypes of endometrial cancer (POLE ultramutated, microsatellite instability hypermutated, copy number low or no specific molecular profile [NSMP], and copy number high or TP53 mutant).⁸ These classifications are often used in ongoing clinical trials and patient care because they allow for better prognostic assessments of outcomes.^{2 , 9} For example, women with the POLE ultramutated subtype, which is more common in younger women than the other subtypes, have survival rates of over 90%.¹⁰

The TCGA molecular subtypes also provide opportunities for ongoing research, as they can be used to develop precision medicine therapies that are tailored for each of the specific subtypes. Some of the treatment options that are under investigation for the different subtypes involve the use of poly (ADP-ribose) polymerase (PARP) inhibitors, anti-angiogenics, and programmed death 1 (PD-1) inhibitors.^{11 , 12} Because women with the POLE ultramutated subtype generally have a good prognosis, studies are also assessing whether treatment deescalation is appropriate for patients with those tumors.¹³ Other areas of active research include defining the potential role of circulating tumor DNA (ctDNA) as a prognostic biomarker for endometrial cancer^{14 , 15} and developing methods for early detection.

Researchers from the Division of Cancer Epidemiology and Genetics at NCI are identifying biomarkers that will allow them to develop noninvasive detection methods for endometrial cancer. This case-control study, called Discovery and Evaluation of Tests in Endometrial Cancer (DETECT), is evaluating the use of vaginal tampons as a sample collection method. The researchers also plan to assess racial disparities in exposures, diagnostic delays, and cancer outcomes.¹⁶