How Endometrial Cancer Differs Between Black and White Women
When Tiffany White was 27 years old, she began experiencing abnormal bleeding and pain. Despite having good health insurance, her initial treatment for endometrial cancer overlooked the aggressive nature of her disease. After months of ineffective hormonal treatment, a second opinion revealed her cancer had spread. Now 31 and in menopause, White's story reflects a troubling pattern in women's health: Black women face dramatically different outcomes with endometrial cancer than White women 3 .
Women affected annually in the U.S.
5-year survival for Black women
5-year survival for White women
The statistics are sobering. While endometrial cancer is the most common gynecologic malignancy in the United States, affecting approximately 69,000 women annually, mortality rates reveal a stark racial divide. Only 63% of Black women are alive five years after diagnosis compared to 84% of White women—representing the largest racial mortality disparity of all cancer types captured in recent American Cancer Society data 3 .
For decades, researchers attributed this gap primarily to socioeconomic factors and later disease detection. However, groundbreaking genomic research is now revealing that the tumors themselves differ fundamentally between Black and White women—a discovery that could transform how we diagnose, treat, and ultimately conquer this devastating disparity.
Endometrial cancer has long been classified into two main types, but genomic research has revealed far more complexity. The traditional classification system distinguishes between:
These are more common, typically less aggressive, and often linked to estrogen exposure and obesity .
Less AggressiveThese include serous and clear cell carcinomas, which behave more aggressively and account for a disproportionate number of cancer deaths 4 .
More AggressiveBlack women are more frequently diagnosed with the more aggressive Type II cancers, particularly serous carcinoma and carcinosarcoma 4 . But the disparity runs deeper than histological classification. The fundamental genetic makeup of the tumors differs in ways that may explain the divergent outcomes.
| Characteristic | Black Women | White Women |
|---|---|---|
| Most Frequently Mutated Gene | TP53 (49%) | PTEN (63%) |
| Common Molecular Subtype | Copy Number High (CNH) | Copy Number Low (CNL) |
| Typical Histology | Serous (more aggressive) | Endometrioid (less aggressive) |
| 5-Year Survival | 63% | 84% |
The revelation that endometrial cancers differ molecularly by race emerged from two pivotal research efforts: The Cancer Genome Atlas (TCGA) and subsequent studies like the UNCseq™ project.
The TCGA analysis in 2018 first uncovered striking differences in mutation patterns. Researchers found that while PTEN was the most frequently mutated gene in Caucasian and Asian women (occurring in 63% and 85% of tumors respectively), TP53 was the predominant mutation in Black women (occurring in 49% of cases) 2 .
This distinction matters profoundly because TP53 mutations are typically associated with more aggressive tumor behavior and worse outcomes.
Landmark StudyThe more recent UNCseq™ study (2025) confirmed and expanded these findings. This institution-sponsored targeted sequencing effort analyzed tumor tissue from 200 endometrioid or serous endometrial cancers, with 169 tumors from White and 31 from Black patients.
The research confirmed that Black patients more frequently had serous and TP53 mutant tumors, while White patients more often had somatic mutations in ARID1A or PTEN 1 6 .
Recent ValidationBlack Women: 49%
White Women: 63%
More common in White women
The UNCseq™ study represents a meticulous approach to understanding endometrial cancer at the molecular level. The research process unfolded through several carefully designed stages:
Researchers identified Black and White patients with histologically confirmed endometrioid or serous endometrial cancers who underwent surgery between February 2011 and September 2016. All participants provided informed consent for tumor tissue analysis 1 .
DNA was isolated from formalin-fixed, paraffin-embedded tumor tissue using specialized kits. Researchers then measured DNA quality using NanoDrop spectrophotometry and TapeStation analysis to ensure sample integrity 1 .
DNA libraries were prepared using the SureSelect XT Kit, involving mechanical shearing of DNA fragments, end repair, adapter ligation, and PCR amplification. The captured libraries were sequenced on Illumina platforms to a depth of approximately 2000X coverage 1 .
Sequence reads were aligned to the human genome using BWA mem, followed by somatic variant calling with specialized algorithms to identify cancer-associated mutations 1 .
Over a median follow-up of 62.4 months, the UNCseq™ data revealed significant clinical differences: Progression-free survival and overall survival were significantly shorter for Black patients 1 6 .
| Finding | Black Patients | White Patients | Statistical Significance |
|---|---|---|---|
| Serous Histology | More Frequent | Less Frequent | p < 0.0001 |
| TP53 Mutations | More Frequent | Less Frequent | p = 0.01 |
| ARID1A or PTEN Mutations | Less Frequent | More Frequent | p < 0.05 |
| 5-Year Survival | Significantly Shorter | Longer | p < 0.04 |
Modern cancer genomics relies on sophisticated technologies and analytical tools that enable researchers to detect the genetic alterations driving these disparities.
| Tool | Function in Research |
|---|---|
| UNCseq™ Panel | Targeted gene sequencing panel covering nearly 500 cancer-associated genes |
| Formalin-Fixed Paraffin-Embedded (FFPE) Tissue | Preserves tumor architecture and DNA for analysis |
| SureSelect XT Kit | Prepares DNA libraries for sequencing by fragmenting DNA and adding adapters |
| Illumina Sequencing Platforms | High-throughput DNA sequencing machines |
| BWA mem Algorithm | Aligns sequence reads to the reference human genome |
| Tumor-normal Pair Analysis | Identifies somatic mutations by comparing tumor DNA to patient's normal DNA |
"Our survivors were saying, 'it's hard, and it's rough, and we have no support.' They were falling off from toxicity and not wanting to complete treatment. What could be called refusal might also be looked at as failure [by the clinician] to communicate."
This insight highlights how understanding both molecular and social factors is essential to addressing disparities.
The genomic differences represent only part of the story. Recent research has revealed that the tumor immune microenvironment also differs significantly between Black and White women with endometrial cancer.
A 2025 computational image and bioinformatic analysis published in Nature Portfolio's npj Precision Oncology examined immune cell spatial patterns in African American versus European American women. The study found that prognostic models performed best when trained and validated using data from the same population, suggesting fundamental differences in immune architecture 4 .
Unsupervised clustering revealed distinct associations between immune cell features and molecular subtypes that varied between racial groups. The research team discovered two distinct gene sets with mutations associated with improved prognosis in African American and European American patients, respectively 4 .
Varies significantly by race, affecting prognosis and treatment response.
Presented at ESTRO 2025, demonstrated that molecular profiling could safely guide adjuvant treatment decisions for women with early-stage endometrial cancer 8 .
Clinical TrialResearchers at Mount Sinai have identified biomarkers that may predict response to combination immunotherapy in recurrent endometrial cancer 5 .
Diagnostic ToolAmerican Cancer Society study aiming to enroll 100,000 Black women to better understand cancer risk and treatment experiences 3 .
Large Cohort StudyThe growing understanding of endometrial cancer's genomic diversity by race represents both a challenge and an opportunity. As the recent research reveals, the solution to disparities lies not in ignoring race, but in understanding its biological and social dimensions.
The disparity between Black and White women with endometrial cancer has widened over 26 years of research 9 . While Black women experience a 39% increase in incidence and 26% rise in mortality, White women have seen only a 2% increase in incidence and 17% rise in mortality 9 .
The genomic research offers promising pathways forward. By recognizing that endometrial cancer manifests differently across racial groups, researchers can develop population-specific risk prediction models and targeted therapies 4 .
As the scientific community continues to unravel the complex interplay of genetics, environment, and social factors in endometrial cancer, there is growing hope that precision medicine may eventually eliminate the racial disparities that have plagued women's health for generations. The message is clear: when it comes to endometrial cancer, one size does not fit all—and recognizing our differences may be the key to saving lives.