Maggie McKay (Host): I'm your host, Maggie McKay. Joining us today is Dr. Megan Hutchcraft, gynecologic oncologist, to discuss endometrial cancer. Thank you so much for being here today, Dr. Hutchcraft.

Megan Hutchcraft, MD: Thanks for having me, Maggie.

Host: Let's just start with would you please identify signs and symptoms of endometrial cancer?

Megan Hutchcraft, MD: Yeah. So, endometrial cancer is one of the few cancers that actually has a really good warning sign. So, abnormal bleeding is the number one sign of endometrial cancer. And that's true for pretty much anyone, any age that could get the disease. It's most common in women who are postmenopausal. So usually, primary sign is bleeding after menopause. And this can be bleeding that's as heavy as a period or heavier than a period, or it can be as insignificant as somebody has a little bit of pink or brown spotting when they wipe, and it only happens one time.

For women who haven't gone through menopause, it can be abnormal periods. So, things like bleeding in between periods or having heavy bleeding that is much heavier than what someone might expect for them to have for a normal menstruation or having multiple periods in one month.

Host: Would you review the increasing prevalence and the mortality of endometrial cancer And its disproportionate impact on women of color and premenopausal women?

Megan Hutchcraft, MD: Yeah. So, endometrial cancer is pretty interesting. I'm obviously biased given my job description. I take care of a lot of these patients. But this is one of the few cancers that's actually increasing in incidents and mortality. Most cancers, you know, we have improvement in screening or improved diagnostics or opportunities for prevention. And this is one that actually is increasing rather than decreasing. And that increase is actually disproportionately affecting premenopausal women and women of color. Specifically, black women, are more likely to have fibroids, which cause a little bit of distortion of the endometrial cavity. And that can really impact the ability for us to use good imaging that may help us to get that diagnosis. And then, from a premenopausal standpoint, one of the reasons we think that it's increasing is related to increasing obesity that's affecting premenopausal women.

Host: What are some risk factors for endometrial cancer that we should recognize and be aware of?

Megan Hutchcraft, MD: Yeah. So, the risk factors for endometrial cancer, there's kind of one main risk factor that we think of when we think of endometrial cancer as one big group. There's a few different types of endometrial cancer, but the most common type of endometrial cancer is called endometrioid, which is where the cells look really similar to the normal endometrium under the microscope. And that one is driven by excess estrogen And the best reason to have excess estrogen that we see in our specific society is obesity. So, the fat cells actually cause testosterone to convert to estrogen, which causes an overabundance of estrogen within the body, which when there's no other hormone called progesterone that's protecting the lining of the uterus, that actually will cause the inside lining of the uterus or the endometrium to grow, which is kind of the main risk factor.

There's other reasons for risk factors for endometrial cancer, which could include things like taking estrogen supplements without progesterone. Progesterone is the protective hormone for the uterus. We fortunately don't see that very much, because anyone who's doing hormone replacement therapy, if they have a uterus in place, should be getting progesterone as well.

There are other risk factors that we're still kind of exploring that may be unrelated to the estrogen aspect, which could include things like hair straighteners, like the chemical straighteners. But that's really kind of still preliminary information.

The last one that I think is important to mention is family history. So, there are some hereditary cancer syndromes that can put people at elevated risk for endometrial cancer. And this includes the Lynch syndrome genes, which can cause hereditary colon cancers and intestinal cancers and urinary tract cancers, as well as endometrial cancer. But we're starting to learn that some of the genes that cause hereditary breast and ovarian cancer, specifically the BRCA1 and BRCA2 gene mutations may also cause an increased risk for uterine cancer. Though that data is a little bit still early and we're still learning more about that.

Host: What if you had endometriosis, and they got rid of it, you know, they took it out? Would cancer reoccur or...?

Megan Hutchcraft, MD: That's a great question, and I'm so glad you asked that because that's a question I get all the time. Actually, endometriosis is an independent risk factor for ovarian cancer, not for uterine or endometrial cancer. The reason for that is probably, because the treatments for endometriosis actually are some protective factors for uterine cancer. And those include things like birth control pills that have that protective hormone, progesterone, in there, or progesterone hormone by itself, which can also help to kind of quiet down endometriosis. And then, also some other treatments like surgical management of endometriosis, which can include removal of the uterus and cervix, fallopian tubes with the ovaries. All of those things would decrease the risk of endometrial cancer as well.

But there still does seem to be an increased risk for ovarian cancer with endometriosis, though it's not as strong as some genetic factors, but certainly can happen with malignant transformation of those endometriosis implants.

Host: What are the substantial racial disparities in this disease?

Megan Hutchcraft, MD: Yeah. So, we briefly talked about this before. One of the things that I had alluded to earlier was the hormone-driven endometrial cancer that's related to obesity and extra estrogen. And then, there's kind of an independent of estrogen type of uterine cancer that look very different under the microscope. And they behave much more aggressively. And those are less frequently caught early, typically require adjuvant chemotherapy or radiation therapy or both, and tend to come back almost no matter what we do in terms of, you know, treatments, though they are getting better.

And what we are finding is that women of color seem to be disproportionately affected by these more aggressive forms of uterine cancer. We're not exactly sure what's causing that. We think some of it could be related to what we originally were using in terms of identifying patients who have this disease, because—and we will talk a little bit more about this later as well—but the American College of Obstetricians and Gynecologists recommendation for folks who have bleeding after menopause in terms of how to work that up is with a pelvic ultrasound. And based on that finding, looking to see if somebody could have an endometrial biopsy or dilation and curettage. And the threshold for doing a biopsy or D&C procedure, the dilation and curettage, was a certain measurement of the lining of the uterus. It had to measure at least four millimeters before a biopsy was warranted.

Now, the big problem here is the studies that evaluated that threshold, that four-millimeter threshold for biopsy, those studies were based out of places like northern Europe, Italy, And in China. And none of those studies included any patients who were black or Hispanic. And that's obviously a huge limiting factor of a major guideline recommendation.

So, this is great timing on this podcast because just maybe a month ago, the ACOG, American College of OBGYNs realized that this four-millimeter threshold was actually disproportionately affecting women of color in terms of failure to identify these aggressive subtypes. And so, now, the new recommendation is anybody who has any bleeding after menopause should have a pelvic ultrasound and a biopsy regardless of the size of the lining of the uterus, which is a huge win because some of those less common or more aggressive uterine cancers, the endometrium may not look thick on a pelvic ultrasound, which may be related to those racial disparities.

Host: So, what are some opportunities to improve diagnostics for endometrial cancer?

Megan Hutchcraft, MD: Yeah. So, one major way to improve the diagnostics is, you know, anybody who has bleeding after menopause, regardless of the size of the lining of their uterus, should have a tissue diagnosis. They should be biopsied with an endometrial biopsy, which can be performed in the office, or have a procedure that's a short procedure, probably a 20-minute procedure in the operating room where we perform a dilation and curettage, evaluate the lining of the uterus under the microscope.

But some of the emerging information that we're seeing, and actually this was just recently, or, I think, maybe in the next issue or something of gynecologic oncology is something that they're developing about looking at the blood, like post-menopausal bleeding blood and looking at it for, you know, it's DNA sequencing to see if maybe that could help us to determine who may need a biopsy and who may be able to avoid it. Because a biopsy, although it's an office procedure, it's a short procedure, it is uncomfortable. And it's definitely something that, if we can avoid that safely, then that would be great.

Host: Well, thank you so much for sharing your expertise. This has been so informative and helpful. Thank you again.

Megan Hutchcraft, MD: Thank you for having me.

Host: Again, that's Dr. Megan Hutchcraft. For more information and to get connected with one of our providers, please visit carle.org or for a listing of Carl providers and to view Carle-sponsored educational activities, head on over to our website at carleconnect.com. That's C-A-R-L-E connect.com. And that wraps up this episode of Expert Insights with the Carle Foundation Hospital. I'm Maggie McKay.