Shining a Light on Uterine Cancer: Rising Incidence and Mortality, Persistent Inequities
Thanks to advances in prevention, screening, and treatment, cancer mortality has declined over the past decades. Uterine cancer, however, stands as a notable exception, with incidence and mortality on the rise. Now the leading cause of death among gynecologic cancers in the United States according to National Cancer Institute estimates, uterine cancer is projected to claim more lives than ovarian cancer in 2026. This disease remains underfunded, understudied, and associated with deep racial disparities.
To better understand this paradox, we spoke with Elizabeth M. Swisher, MD, the 2026-2028 Chair of the AACR Cancer Prevention Working Group (CPWG) steering committee. She explained why uterine cancer is a growing public health concern in this country and around the world and discussed some of the steps that can be taken to prioritize funding, research, and public awareness.
Under her leadership, the CPWG is advocating for uterine cancer to have its own recognition independent of other gynecologic cancers.
“Just like we don’t talk about prostate cancer and all genitourinary cancers together as one group, the same approach should apply to gynecologic cancers: Cervical, ovarian, and uterine cancer, for example, have completely different screening, prevention, and treatment approaches, so breaking them down is a great first step toward better awareness,” Swisher said.
Swisher is the Torkelson Family Endowed Chair and a professor in the Clinical Research Division of Fred Hutch Cancer Center and in the Division of Gynecologic Oncology of the University of Washington School of Medicine.
What Roles Do Obesity and Hormones Play?
When people talk about uterine cancer, they usually refer to endometrial cancer, the most common type, which forms in the inner lining of the organ, called endometrium, and accounts for approximately 95% of all cases; uterine sarcoma, which begins in the muscular layer of the uterus, is a rarer and more difficult to treat type.
Obesity and metabolic syndrome are the leading preventable risk factors for a portion of endometrial cancers, known as hormone-driven or type 1 endometrial cancer or endometrioid carcinoma, which usually have better outcomes than other subtypes. Obesity rates have risen significantly in the United States over the past several decades, overlapping with and partially driving the increased rates of endometrial cancer. Metabolic syndrome encompasses a cluster of conditions including abdominal adiposity (excess fat around the stomach and lower torso), hyperglycemia, elevated lipids, and hypertension, and is a major risk factor for endometrial cancer in addition to heart disease and diabetes.
Swisher explained that women with more adipose tissue tend to have higher levels of estrogen, the hormone that drives the thickening of the lining of the uterus during the first part of the menstrual cycle. This can create an imbalance with progesterone, which has a protective effect on the uterus. This imbalance stimulates continuous proliferation of endometrial cells, increasing the risk of cancer. Obesity and metabolic syndrome are also associated with insulin resistance and hyperinsulinemia, which can further promote tumor growth.
“Irregular and less frequent periods associated with obesity or metabolic syndrome can be a sign of hormonal dysregulation that will ultimately put the uterine lining at risk for transformation,” Swisher noted. She added that these conditions can manifest in young girls, so having irregular periods is something that should be brought to attention because if it is recognized and modified, it is possible to reduce the risk of endometrial cancer down the road.
In addition to obesity and metabolic syndrome, increased risk for type 1 endometrial cancer is linked to other factors that lead to prolonged exposure of the endometrium to estrogen, including reproductive aspects such as starting periods early, entering menopause later, and never giving birth; conditions like polycystic ovary syndrome; taking tamoxifen to treat breast cancer; and estrogen-only hormone replacement therapy.
Other risk factors for endometrial cancer include older age, a family history of the disease, and Lynch syndrome.
Why Do Black Women Face Worse Outcomes?
Swisher pointed out that uterine cancer exhibits one of the most pronounced racial disparities in cancer outcomes in the country, with Black women being more likely to die from this cancer type than white women despite lower overall incidence.
The excess mortality is mostly driven by higher prevalence of aggressive histologic subtypes among Black women, including uterine serous carcinoma, carcinosarcoma, and clear cell carcinoma. These types of non-endometrioid endometrial cancer or type 2 endometrial carcinoma have a higher mortality than type 1, and disproportionately affects Black women.
“We don’t really know why,” explained Swisher. She hinted to a combination of biological, economic, healthcare-related, and environmental factors. “For example, Caribbean-born Black women have lower risk of endometrial cancer type 2 than Black women born in the United States. This suggests that there may be environmental factors at play, and we need a lot more research to identify the factors that create this disparity.”
Delayed diagnosis is another aspect likely contributing to worse outcomes in Black women. “Partly, that has to do with the fact that the algorithm for how we evaluate abnormal vaginal bleeding was validated in a predominantly white population,” explained Swisher.
The first step for evaluating abnormal bleeding, the hallmark symptom of uterine cancer, is often transvaginal ultrasound that assesses the thickness of the lining of the uterus. Black women have a higher prevalence of uterine fibroids, noncancerous tumors that form in or on the wall of the uterus.
Since these growths can obscure the uterine lining and reduce the test’s ability to detect cancer, ultrasound is less effective as a diagnostic workup for Black women than for white women and may miss cancer. Therefore, an endometrial biopsy is the gold standard, explained Swisher: “It is a minimally invasive procedure that can be easily done during an office visit.”
Community awareness about normal and abnormal bleeding is critical, she added. “If women have been brought up to think that it is normal to bleed well into their 60s, because their mother and their aunts had this type of bleeding due to fibroids, this early sign of cancer won’t be recognized,“ she said.
Rising Deaths, Limited Research Dollars
Despite the increasing trends in incidence and mortality, uterine cancer research receives less funding than other cancer types, Swisher noted.
“I think the underfunding of uterine cancer research is a symptom of the underfunding of women’s healthcare in general. There are other benign conditions that affect the uterus that are massively underfunded, such as uterine fibroids, endometriosis, pelvic pain, and abnormal bleeding. All these conditions are very common but do not receive sufficient attention,” Swisher said. “The uterus, in particular, is something we tend to ignore because we’ve been taught for most of our lives to not talk about our periods and not talk about healthy reproductive function. I think there should be more focus on reproductive health not restricted to childbearing but encompassing all the reproductive organs and functions throughout the lifespan of a woman.”
Swisher partly attributed the funding gap to the fact that uterine cancer outcomes are worse for Black women, a population whose health care issues have been historically underfunded.
What Can Women Do to Reduce THeir Risk of Uterine Cancer?
When detected early, uterine cancer is highly curable, with a five-year survival rate greater than 86%. However, survival drops drastically to less than 20% for advanced-stage disease. Therefore, prevention and early detection are critical.
“A healthy body weight and exercise are important goals to reduce risk. Regular gynecologic care and recognition of abnormal bleeding patterns are also crucial,” said Swisher.
The most common warning sign of uterine cancer is abnormal vaginal bleeding. Swisher emphasized the importance of education early in life about what normal periods are and what is outside the normal range to help counter misconceptions. “In addition to abnormal bleeding patterns often being normalized by family members or by the patient themselves, some physicians and healthcare providers also tend to ignore women who complain of very heavy bleeding and pain, and they discount those symptoms as ‘bad periods,’” Swisher said.
“Even asking women if their periods are normal might not be enough, because the doctor and the patient might have different definitions of what normal is,” Swisher emphasized. “Having providers ask more specific questions to find out what people’s bleeding patterns are would be helpful.”
Education and awareness are critical during the menopausal transition too. “The most common time when endometrial cancer has a delayed diagnosis is perimenopause because all irregular bleeding at that time is just blamed on the hormonal changes,” said Swisher. She explained that while some variation in the timing of periods is common during the menopausal transition, bleeding in between periods or periods that suddenly become much longer might be a warning sign. “Average age of menopause is around 51, up to 55. Beyond that, no amount of bleeding is normal and should be evaluated.“
Advancing Our Understanding of the Disease and Effective Treatments
The addition of immunotherapy to the therapeutic options for uterine cancer has made a substantial difference, said Swisher.
Along with colon cancer, endometrial cancer has the largest fraction of mismatch repair deficiency (MMRd) and microsatellite instability (MSI) of any solid tumor, molecular features that point to better response to immunotherapy. However, immunotherapy clinical trials for uterine cancer arrived later than for other cancer types, including ovarian cancer, which hasn’t historically been responsive to this approach, Swisher noted.
“I think the lagging in treating MSI-high or MMRd endometrial cancer behind colon cancer is another indication of the lack of attention toward endometrial cancer.”
Clinical trials eventually demonstrated that immunotherapy is beneficial not only for patients with MMRd endometrial cancers, but for non-MMRd cancers as well, in combination with chemotherapy.
“The success of adding immunotherapy to endometrial cancer treatment has not only transformed the field and benefited patients, but it has also helped establish endometrial cancer as a good target for drug development,” noted Swisher. “As a result, there are now more drugs being tested for endometrial cancer, including antibody-drug conjugates and other types of immunotherapy, which I’m excited to see in the future.”
Editor’s note: The CPWG recently launched a LinkedIn page for the group where members can share exciting new findings, new funding opportunities, and upcoming conferences that may be of interest to the cancer prevention community.
