MD Anderson Cancer Center
Lisa Garvin: Welcome to "Cancer News Line", a podcast series from the University of Texas - MD Anderson Cancer Center. "Cancer News Line" helps you stay current with the news on cancer research, diagnosis, treatment, and prevention, providing the latest information on reducing your family's cancer risks. I'm your host, Lisa Garvin. Today our guest is Dr. Shannon Westin. She is an assistant professor of gynecologic oncology here at MD Anderson, and our subject today will be uterine cancer. So, Dr. Westin, first of all, let's clear up the distinction between uterine and endometrial cancer. Are they the same name for, different names for the same cancer, or two different cancers -
Dr. Shannon Westin: That's a great question. So essentially they are two names for the same cancer. The most common uterine cancer is endometrial. So when you think about the uterus, it has different layers. The inside layer, which is the layer that builds up when a woman becomes pregnant, is called the endometrium, and that she where about 90, 95 percent of cancers will arise. And so we often, when we talk about cancers in general we'll just say endometrial cancer. There's a small subset of cancers that will arise in the muscle layer of the uterus. Those are called sarcomas, and those will be about five to seven percent of all uterine cancers in general -
Lisa Garvin: What are the overall statistics for uterine cancer in the U.S. -
Dr. Shannon Westin: So including both uterine as well as endometrial, we would see, in 2012, the ACS estimated about 47,000 women would be diagnosed with endometrial cancer and approximately 8,000 will die from the endometrial cancer -
Lisa Garvin: And you say actually the numbers have stayed the same, the diagnosis have stayed the same and maybe increased slightly. What's going on there -
Dr. Shannon Westin: Yeah. So contrary to what we've been seeing in other cancer types where the incidence is reducing based on prevention efforts or just information that's getting out to the public, we're seeing at least a plateau if not somewhat of a rise in the incidence of endometrial cancer, and that really is we think strongly correlated with the epidemic of obesity in our country and across the world. Endometrial cancer, the endometroid type especially is tightly linked to estrogen and to an excess of estrogen, and that can be caused by women that are taking extragoneous estrogen, like pills, but also can be related to what we call endogenous estrogen, which means your body's making its own estrogen, and we know that when women have extra fat cells or [inaudible] cells that those cells actually convert hormones into estrogen. And so we see that tight link between obesity and endometrial cancer, and we anticipate that that is one of the major reasons that we're not seeing any change.
Lisa Garvin: As far as diagnosing uterine cancer, I know that cervical cancer and ovarian is particularly, the symptoms can be kind of silent. Are the symptoms obvious with uterine cancer -
Dr. Shannon Westin: Yes. Actually that's one of the best, I don't know if you can call it the best parts of having endometrial cancer is that patients generally will present with bleeding. And so a lot of times before the tumor is too spread, so when it's still early, stage I, confined in the uterus, they'll be having bleeding, and we can capture it ahead of time and get them treated. So that is one, the major symptom that we do see with uterine cancer. Other symptoms would be things like discharge, pelvic pain, but the most common is bleeding.
Lisa Garvin: Do we tend to catch uterine cancers at an early stage?
Dr. Shannon Westin: About ninety percent will be captured at stage I.
Lisa Garvin: And I think, it's generally an older women's disease. Does this disease creep down into people below the age of 40?
Dr. Shannon Westin: Absolutely. You know, the median age is about 60 of diagnosis, however, we do see a proportion of patients I think at the last study that I read, it was about 15 percent or so that are less than 40. So this is, you know, it's becoming a younger women's disease, and that's because it's tightly related to obesity. In general, the patients that we see that are younger with this disease tend to be obese. There's also a heredity syndrome that can put women at a higher risk of developing uterine cancer, and in general, those patients will also be younger, but that's only in about five percent of uterine cancers -
Lisa Garvin: Is that Lynch syndrome -
Dr. Shannon Westin: Right. So it used to be called heredity non-polyposis colorectal syndrome, but now it's called Lynch syndrome, and that's because in women, although the colon cancer is, can happen in about forty to sixty percent of women, endometrial cancer can also occur in about forty to sixty percent of those women. And actually in a study that we did here, we found that often the endometrial cancer was the centenal [phonetic] cancer or the first cancer for these patients and was the identifying cancer for these patients. And so they adjusted the name so as not to be misleading because those two cancers were so common in women that have Lynch syndrome.
Lisa Garvin: Now since it is creeping into a younger population, obviously, fertility and fertility sparing becomes very important -
Dr. Shannon Westin: Absolutely -
Lisa Garvin: How do you address, how and when do you address fertility issues -
Dr. Shannon Westin: Well, this is actually an area of great interest for me. It's an area I'm doing research on. So this is a huge area of interest because a lot of these women, some of the other risk factors for endometrial cancer are no children, you know, no menopause, long time exposed to your menstrual cycle. And so these women would like to become pregnant, and then when they're through their workup to become pregnant, they're found to have an endometrial cancer. Usually these are early, and if they are early, there are conservative options for these patients. The main option that we've been looking at or that has been kind of well established is progesterone. So basically you have an excess of estrogen, and progesterone is the hormone that counteracts that. And so you give these patients progesterone to try to counteract that. Unfortunately, it's not always effective, but it's fairly effective. In addition, it can hard for patients to be compliant with it because there are a lot of symptoms that they get from progesterone - nausea, headaches, weight gain - and in a population that's already obese, that can be a very big issue. And so we have been exploring at Anderson utilizing the Mirena IUD or [inaudible], which is a type of progesterone intrauterine device. Now this is something that's used for, FDA approved for contraception and bleeding, but we're trying to repurpose it to potentially treat patients with early endometrial cancer. It sits in the uterus, it lasts for five years, and we're currently performing a Phase II trial to see if it's effective and safe.
Lisa Garvin: But you would have to remove that if they were wanting -
Dr. Shannon Westin: Right -
Lisa Garvin: To become pregnant, what happens then -
Dr. Shannon Westin: Right. So that's the million dollar question. So in general what we've been doing is treating these patients for a year. If they clear, and they're ready to become pregnant, we can remove the IUD. Let them go on to try to achieve pregnancy, however that might happen, and then ultimately this would be a patient that we would advise, would need a subsequent hysterectomy or removal of the uterus once she was done with fertility.
Lisa Garvin: And can you harvest eggs like you can with, I know with males you can obviously bank sperm. Can you harvest eggs from women who may be concerned about their fertility afterwards -
Dr. Shannon Westin: Absolutely. That's, it's a growing area and actually we've been working on developing our [inaudible] fertility program here at MD Anderson to be able to offer that type of thing.
Lisa Garvin: And in how many cases is the uterus saved? I mean, it seems like especially in the olden days they were just, like, just take it out.
Dr. Shannon Westin: And that's still true. For the majority of patients, we would urge hysterectomy because that is a definitive treatment. I don't know if I have percentages, but there are a significant proportion of patients, and if you look in the literature, maybe up to 75 percent of patients will have some response. It's the durable response that we're looking for, and in about 25 percent or so, it will come back. And so that's the trick is finding that window of opportunity to achieve fertility or achieve what you're looking for and then get that uterus out.
Lisa Garvin: And I'm assuming that the surgery, either alone or in combination with others, is front-line therapy?
Dr. Shannon Westin: Right. So front line is surgery, and then based on the findings from surgery, this is a surgically-staged disease. So at the time of surgery, the uterus is removed, cervix, fallopian tubes, ovaries, and potentially lymph nodes from the pelvis and periaortic [phonetic] area or around the aorta. Based on the results of that pathology, the patient will be potentially treated with different therapies. Some patients don't require anything. If it's a very early tumor, it's not growing into the wall of the uterus, it's not involving any of the additional structures. But in patients that the tumor is growing into the wall of the uterus or has other, you know, high-risk features, they potentially might get radiotherapy, either just to the top of the vagina or even to the entire pelvis, and that can be combined with chemotherapy in certain patients.
Lisa Garvin: You do say it does tend to recur in about 25 percent of the population -
Dr. Shannon Westin: So with early. So with early tumors, if you're conservatively trying to treat them. So in those patients being treated with oral progesterones or other progesterones, you can achieve a complete response, but there's a high chance that it's going to come back. Now if we're looking at recurrence in general, the recurrence rates are I would say about 15 to 20 percent in early stage disease. So a majority of patients will do very, very well, and that's where we get our excellent survival from, but it's, there's a small group of patients with early stage disease that will recur, and then, of course, advanced stage. So this is stage III and IV, these are people that have tumor in their lymph nodes or in the abdomen or pelvis or lung or bladder. Those patients tend to do more poorly. They, we can achieve complete responses, but it's a much lower rate, and in those cases that we do, their chance of recurrence is much higher.
Lisa Garvin: What about adjuvant therapy? Do you often follow up surgery with either radiation or chemo -
Dr. Shannon Westin: So based on the pathologic results, we might treat with radiotherapy to the top of the vagina or to the pelvis. Chemotherapy has been slowly increasing. We've been increasing our incorporation of chemotherapy, sometimes just along with radiotherapy and sometimes after, and that would be in patients with extremely high-risk features, either histology types that are high risk like serous tumors or clear cell tumors or in patients that have involvement of the ovaries, the [inaudible] structures, or in the lymph nodes, the pelvic or periaortic lymph nodes.
Lisa Garvin: What sort of research is being done on targeted therapies? Are there any targets -
Dr. Shannon Westin: Yes -
Lisa Garvin: For targeted therapy -
Dr. Shannon Westin: Actually endometrial cancer has a wealth of opportunities for targeted therapies. There are many studies coming out right now. The TCGA is putting out some information about uterine cancer, but what we found here at MD Anderson through our uterine spore is that almost eighty percent of these patients have some type of aberration which could potentially be targeted. The majority of those patients have aberrations in what's called the PI3 [inaudible] AKT pathway. This is a hot, hot pathway that basically is involved with survival, and, you know, it's what makes cancer turn into cancer. And there are many drugs that are being developed along this pathway, different inhibitors of different points along the pathway, and we think that these hold a great promise for endometrial cancer. The studies are still pretty early. The most developed of these have been the M tour inhibitors, which is a lower player along the pathway, and the responses have been modest. We're looking at anywhere from 10 to 15 percent response rates, but the stable disease rate, which is a patient is on the treatment for a significant period of time without growth of cancer, those tend to be a little bit better approaching, you know, thirty or forty percent. So we're certainly starting to scratch the surface. That's not the goal we have, but we're starting to see a signal, and so there's multiple drugs that are being developed in this area, and we're very hopeful to get to look at them in endometrial cancer.
Lisa Garvin: Great. Thank you. Is there anything in summary you would say to women who might be at risk for uterine cancer, what's your message to them?
Dr. Shannon Westin: I would say weight loss is imperative, and, you know, knowing what your body mass index is. Go on the Google and figure out how to calculate it. You want to get it below 25, and if nothing else, below 30, OK, and that could help reduce your risk. If you want to talk with your doctor, if you're on hormone replacement therapy, make sure that it's safe for you, and that it's appropriate for you. And any bleeding after you've gone through menopause should be evaluated immediately. And heavier regular periods should also be evaluated with your doctor. So I think that the main take home point is that we can catch this early. So if you've got any symptoms, you just got to get into your doctor and get it evaluated.
Lisa Garvin: Great. Thank you very much, Dr. Westin -
Dr. Shannon Westin: Thanks so much for having me.
Lisa Garvin: If you have questions about anything you've heard today on "Cancer News Line", contact Ask MD Anderson at 1-877-MDA6789, or online at MD Anderson dot org slash ask. Thank you for listening to this episode of "Cancer News Line". Tune in for the next podcast in our series.
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