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BackTable / OBGYN / Article
Rising Endometrial Cancer Incidence: What’s Causing the Increase?
Faith Taylor • Updated Nov 27, 2024 • 33 hits
Endometrial cancer is on track to surpass ovarian cancer as the deadliest gynecologic cancer. Its rising incidence and mortality rates in recent years are largely fueled by population-wide risk factors like obesity, an aging population, and persistent healthcare disparities. As a result, endometrial cancer has become an increasingly urgent public health issue.
Gynecologic oncologist Dr. Amanda Fader and gynecologist Dr. Matthew Powell explain the rising rates of endometrial cancer through an overview of the subtypes, epidemiology, and healthcare disparities commonly associated with this disease. This article features excerpts from the BackTable OBGYN Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.
The BackTable OBGYN Brief
• The endometrioid subtype of endometrial cancer is the most common form of endometrial cancer, characterized by hormone-receptor positivity and often presenting as lower grade and early-stage disease.
• The non-endometrioid subtype of endometrial cancer is a rare and aggressive form, including serous, carcinosarcoma, and clear cell cancers, associated with poor prognosis and higher mortality
• Endometrial cancer incidence and mortality are increasing, driven by obesity, an aging population, and higher rates of aggressive non-endometrioid subtypes.
• Obesity increases estrogen levels, promoting endometrial lining growth and elevating cancer risk, with lifestyle changes contributing to the epidemic.
• Additional risk factors for endometrial cancer include tamoxifen use, diabetes, hypertension, infertility, polycystic ovary syndrome, and nulliparity.
• Birth control pills reduce risk of endometrial cancer, but decreased usage and declining hysterectomy rates are now contributing to the overall rise in cases.
• African American women with endometrial cancer face worse outcomes, often due to higher rates of non-endometrioid subtypes. This disparity is due to factors such as environmental influences, decreased hysterectomies, and limited awareness of symptoms.
Table of Contents
(1) Types of Endometrial Cancer: Endometrioid vs Non-Endometrioid
(2) Endometrial Cancer Epidemiology: A Closer Look at Obesity & Aging
(3) Endometrial Cancer Disparities: Racial, Environmental & Healthcare Factors
Types of Endometrial Cancer: Endometrioid vs Non-Endometrioid
Endometrial cancer is broadly categorized into two primary subtypes: endometrioid and non-endometrioid cancers. Endometrioid cancers, which represent the majority of cases, are often estrogen and progesterone receptor-positive and frequently associated with obesity. While typically presenting as low-grade and early-stage tumors, a subset can demonstrate advanced stage or higher-grade pathology.
Non-endometrioid cancers, by contrast, encompass rarer and more aggressive subtypes, such as uterine serous carcinoma, carcinosarcoma, and clear cell carcinoma. These variants are characterized by poorer prognoses and distinct molecular profiles.
[Dr. Amy Park]
Amazing. We're so lucky to have you guys on this. I've been hearing about this for the last couple of years. I'm a urogynecologist, so I don't have any content expertise in this topic. You touched on this, Amanda, a little bit earlier, but can you describe the different types of endometrial cancer and what the epidemiology has been historically?
[Dr. Amanda Fader]
Yes. There's two basic categories of endometrial cancer, endometrioid and non-endometrioid cancers. The vast majority of patients that are diagnosed with endometrial cancer have the endometrioid subtype. These tumors tend to be estrogen and progesterone receptor-positive. They tend to develop in patients with overweight or obesity, and in many cases are a low grade and early stage. Not in all cases, however. There's certainly a subset of patients with this disease that have more advanced stage or higher grade tumors, but they represent the majority of patients with this disease.
Whereas the non-endometrioid subtypes are some of those poor prognostic, rare types of cancer, like the uterine serous, the carcinosarcoma, the clear cell subtypes, and some of the mixed tumors as well. We're now looking at endometrial cancers, not just in terms of these histologies, but in terms of molecular differentiation to really help us understand the biology behind the tumors and what patients with these tumors might best respond to in terms of treatment.
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Endometrial Cancer Epidemiology: A Closer Look at Obesity & Aging
Endometrial cancer has risen in both incidence and mortality rates, driven by two key factors: the rising obesity epidemic and an aging population. Obesity contributes to elevated estrogen levels due to increased peripheral hormone conversion, promoting endometrial proliferation and, over time, carcinogenesis. Concurrently, an aging demographic, particularly among the baby boomer generation, has led to a surge in cases.
In the U.S., where 15% of global cases occur, endometrial cancer is poised to overtake colon cancer as the third most common cancer in women by 2030. Although 80% of patients present with disease confined to the uterus and fare well, the remaining 20% face challenges with metastatic disease. Clinicians must remain vigilant, as endometrial cancer is not exclusive to individuals with obesity. In fact, high-grade, aggressive subtypes of endometrial cancer disproportionately affect African American and Black women.
[Dr. Amy Park]
What's going on right now? It sounds like the epidemiology, has that changed or has it been rising rates in the type 2 or the non-endometrioid cancers? What's going on right now?
[Dr. Matthew Powell]
The two main things going on. One, we have an obesity epidemic in this country, and that's driving elevated risks of endometrial cancer. Most of that is through increased levels of estrogen. As people are heavier, they get more conversion of some hormones into weak estrogens, and this causes the lining of the uterus to grow and grow and grow. Over time, that accumulates enough damage to result in cancer. The obesity epidemic is certainly one.
The other thing is we have an aging population. As we get older, we're more likely to get these cancers, and there's more people at risk. The baby boomer population that's now in the retirement phase, that's where we're seeing a lot of cancers. If we look across the world, there's about 425,000 cases of endometrial cancer. In the US, we represent about 15% of all the cases worldwide. Really, with our obesity epidemic and our aging population, we see a large portion of these cases.
It is a disease somewhat of the Western world, but about 3% of all women will get endometrial cancer in their life. Thankfully, the vast majority will have disease confined to the uterus and do well. About 80% of patients do well, but unfortunately, 20% of patients will have trouble with this cancer, and where they can get metastatic disease and ultimately succumb to the cancer.
It is now our most deadly cancer. Ovarian cancer used to be the most deadly, and then this year, it looks like endometrial cancer is going to surpass that. As you mentioned, it's because of these higher-grade, higher-risk types. These are the types that not only affect our older patients, but also disproportionately affect our African-American and Black patients. We have a big effort now to try to sort out why and try to get the word out that abnormal bleeding is a big problem, and that needs to be addressed by patients.
[Dr. Amanda Fader]
If I may add to that, endometrial cancer is the fourth most common cause of cancer in women in the US. Given some of these trends that Matt is talking about, we are set in 2030 to see endometrial cancer overcome colon cancer to become the third leading cause of cancer in women. These are really, really disturbing, both incidence and mortality trends.
When you look at all cancers together, while most solid tumors in the world are decreasing in incidence or plateauing in incidence, endometrial cancer is one of the only cancers that's rising in both incidence and mortality for many of the reasons that Matt described. This is a real call to action here and a huge public health threat for women.
[Dr. Matthew Powell]
We should probably point out that you don't have to be overweight to get this cancer either. It's not solely due to that, but that's a big factor in developing the cancer. Nobody's safe, I think, is the issue with endometrial cancer with it being such a high prevalence. 3% of women get this cancer in the United States.
Endometrial Cancer Disparities: Racial, Environmental & Healthcare Factors
Patients of African ancestry face nearly double the mortality risk from endometrial cancer, driven by a higher prevalence of aggressive non-endometrioid subtypes when compared to other patient populations. This disparity may also be driven by population-specific environmental exposures. Dr. Powell cites hair-straightening chemicals as one potential driver. Recent shifts in medical practice, such as declining hysterectomy rates, may also play a role.
Beyond racial disparities, other factors also contribute significantly to the increased incidence of endometrial cancer. Increased tamoxifen use among breast cancer survivors elevates the risk of endometrial cancer. Comorbidities such as diabetes and polycystic ovarian syndrome further exacerbate hormonal imbalances, increasing susceptibility. Declining birth rates and reduced utilization of protective oral contraceptives also contribute to this heightened risk. Addressing these disparities requires not only research into biological and environmental mechanisms but also improved community and provider education on early detection and risk management strategies.
[Dr. Amy Park]
It sounds like what you alluded to, Matt, is that it's really powered by a lot of-- there's a disparity in who's getting the more lethal cancers or the ones with the worst prognosis. I know you alluded to this earlier, but can you go do a deeper dive? What's going on there?
[Dr. Matthew Powell]
We don't entirely understand why there is a racial disparity. We knew patients with African ancestry tended to do worse. They didn't have this higher rate of getting the cancer, but when they got the cancer, it tended to be this non-endometrioid type and was much more associated with deaths, about twice the risk of dying when they do have endometrial cancer.
We actually have a lot of research ongoing looking at environmental factors, molecular factors. I know there was some implications of hair straightening chemicals that may be a portion of this. Then there's a declining rate of hysterectomy in this country. When we correct for hysterectomy, we see this rate really go up. People that still have their uterus are at very high risk. We're doing a lot less hysterectomies than we did in the past. I think that's another part of what's going on.
[Dr. Amy Park]
Oh, that's so fascinating. I hadn't even thought about that.
[Dr. Amanda Fader]
I think when we were all in training, there was an instance of 600,000 hysterectomies a year. I think the most recent data shows about 450,000 are being performed now with so many interventional and conservative management techniques. In addition to that, you're seeing increased tamoxifen use amongst breast cancer survivors, for example. As studies have shown that prolonged tamoxifen use may be beneficial to select breast cancer survivors, we know that tamoxifen is also a risk factor for endometrial cancer and increases that risk by fourfold.
All of these factors, coupled with the lack of community knowledge about the symptoms of the disease and when to present for care, and lack of knowledge by some providers as well, not just by persons in the community. We have just a cluster here of different factors converging to lead to these increases in rates.
[Dr. Amy Park]
Does the decrease in childbearing or less exposure to birth control pills or any of that stuff also contribute? I don't know if those are factors or not.
[Dr. Matthew Powell]
Birth control pills do help prevent endometrial cancer, but you also see in women that have not had children, they have an increased risk of endometrial cancer. Also, women who've had some infertility, typically a diagnosis of polycystic ovarian syndrome, hypertension, and diabetes also are independent risk factors for the development of endometrial cancer. We see a lot of these patients have diabetes, they get an abnormal hormonal syndrome going on that leads to this increased risk of endometrial.
Podcast Contributors
Dr. Amanda Fader
Dr. Amanda Fader is a professor of gynecology, obstetrics and oncology and a gynecologic oncologist with Johns Hopkins Medicine in Baltimore, Maryland.
Dr. Matthew Powell
Dr. Matthew Powell is a professor of obstetrics and gynecology and a gynecologic oncologist with Washington University in St. Louis, Missouri.
Dr. Amy Park
Dr. Amy Park is the Section Head of Female Pelvic Medicine & Reconstructive Surgery at the Cleveland Clinic, and a co-host of the BackTable OBGYN Podcast.
Cite This Podcast
BackTable, LLC (Producer). (2024, June 25). Ep. 58 – Understanding Rising Endometrial Cancer Rates [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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