Understanding the Relationship Between Estrogen and Uterine Cancer

00:00:00:00 - 00:01:08:21
Unknown
Hello everyone, and welcome to the webinar. Understanding the relationship between Estrogen and Uterine Cancer and inevitably more outreach and uterine program coordinator. We share in the chat what we are joining us from today before the presentation begins, I like to tell you a little bit about share. Share is a national nonprofit that supports, educates and empowers anyone who has been diagnosed with women cancers and provides outreach to the general public about signs and symptoms.

00:01:08:23 - 00:01:39:01
Unknown
Because no one should have to face breast, ovarian, uterine, cervical or metastatic breast cancer alone. For more information about upcoming webinars, support groups and our helplines, please visit our website and share can support at work. All participants will be muted during the presentation. Dr. Alex finishes. When Dr. Phillips finishes presenting, we will begin the Q&A discussion. Feel free to comment in the chat.

00:01:39:03 - 00:02:04:06
Unknown
You can also use the chat or Q&A section at the bottom of your screen to ask questions. Please remember that DRS Alex is unable to give specific medical advice, so please keep your questions general in nature. We also have a closed caption available. You can enable this feature by clicking the live transcript button on the bottom of your screen.

00:02:04:11 - 00:02:28:08
Unknown
Selecting the subtitle Option. This webinar is being recorded and will be available on the Share website soon, and that I like to hand it over to today's speaker to introduce herself. Back to the legs. Hello and welcome to everyone and thank you so much to those of you who are joining us today. I appreciate all of you adding in where you're from.

00:02:28:08 - 00:02:56:09
Unknown
It's kind of fun to see all these different locations around the U.S. and so much representation. And even before I introduce myself, I just want to thank the sheer organization for asking me to do this webinar today. I have found that as a guy, an oncologist share has provided so many resources to my patients and, you know, their online education through these different free webinars and online events are just such a wonderful resource to patients.

00:02:56:11 - 00:03:20:16
Unknown
And so I really am excited to be here with all of you today. They created this very nice introduction slide for me. I'm not going to read it directly, but I am a board certified gynecologic oncologist and I currently work at the Icahn School of Medicine at Mount Sinai in New York City. I, as it mentions, here am a gynecologic surgeon.

00:03:20:16 - 00:03:52:02
Unknown
I do a lot of robotic surgery and I treat all types of gynecologic cancer. I'm also very passionate about helping patients enroll in clinical trials. And you know, as a gynecologic oncologist, we often work in a very multidisciplinary team to help provide the best patient care that we can. So without further ado, I'm going to see if I can share my screen at this time and pull up some slides that I created for us to dive right in.

00:03:52:04 - 00:04:11:10
Unknown
I do look at this as a conversation, so, you know, I welcome questions throughout this dialog that we're all the happy having today. And so if there are any questions that you'd like to ask at any time, please feel free to use the chat function of Zoom or, you know, raise your hand and we can always call on you.

00:04:11:10 - 00:04:34:15
Unknown
I don't mind stopping at various points or at the end of the presentation today. I do imagine we'll have some extra time where if we need to go back to anything in particular, we can revisit any point to be able to talk further about any of these topics that will be discussing today. So I was asked to discuss the relationship between estrogen and, you know, really started as uterine cancer.

00:04:34:15 - 00:05:00:15
Unknown
But I decided to focus primarily on endometrial cancer. And the difference just being that, you know, the uterus is obviously the entirety of the womb organ for women. And the endometrium is that inner lining of the uterus, which endometrial cancer then is the most common type of cancer that can originate inside a uterus.

00:05:00:17 - 00:05:23:06
Unknown
All right. So just real quickly before we get started, as a quick disclaimer and some disclosures, obviously, any answers to questions that come about today represent my own personal opinion and are based on current and usual practices in the field of gynecologic oncology. And obviously, I will do every effort possible to make sure the accuracy of all information that's provided.

00:05:23:08 - 00:05:55:18
Unknown
I have no financial disclosures as it regards to this topic. So the learning objective of today's talk, my hope is that the participants who are here today at the conclusion of this session will be able to kind of summarize the current state of endometrial cancer better understand the role of sex, steroids in the development, prevention and treatment of endometrial cancer, and discuss some targeted treatment options for endometrial cancer and have a better understanding of these options.

00:05:55:20 - 00:06:35:01
Unknown
So we'll start with just some background on endometrial cancer. So endometrium cancer is the most common gynecologic malignancy in the developed world. Approximately 3.1% of women will be diagnosed with endometrial cancer at some point during their lifetime. So that equivalent to about one in every 32 women here in the United States. In 2022, it was estimated that there would be approximately 65,950 new cases of uterine cancer, and an estimated 12,550 people will die of this disease.

00:06:35:02 - 00:07:11:13
Unknown
In North America, uterine cancer ranks fourth amongst all cancers and ninth amongst the most deadly cancers. Most cases of endometrial cancer are diagnosed in women between the ages of 45 to 74, with the reported median age of diagnosis of 63, endometrial cancer can be categorized broadly into two types that differ predominantly in terms of their epidemiology, genetic profile, prognosis and even treatment.

00:07:11:15 - 00:08:09:23
Unknown
The more prevalent type one cancer or endometrial adenocarcinoma is the most common histologic type of intermediate cancer and accounts for more than three fourths of all the cases of type two cancers are categorized by typical clear cell or papillary serous histology as most cases of type one cancer are low grade and are often confined to the uterus. When diagnosed, the precursor lesion of a type one cancer is an entity called Endometrial Intraepithelial Neoplasia, which was previously known as complex, atypical, hyper plasma type one cancers are associated with unopposed estrogen exposure, whereas the less common type two cancers are usually not associated with hyper estrogenic factors.

00:08:10:00 - 00:09:02:05
Unknown
So as such, type one cancers frequently are found to be positive for estrogen and progesterone receptors, whereas type two cancers tend to not have this positive receptor status and tend to be negative for air and processed in this classification system of utilizing two different types of endometrial cancer dates all the way back to as far back as the 1980s, where I could see the initial description kind of breaking down this entity into these two processes with our growing body of knowledge today, you know, this is becoming more of a historic classification system and we're moving more into a molecular classification system as we better get to understand both of these processes.

00:09:02:07 - 00:09:38:07
Unknown
The diagnosis of individual cancer has increased worldwide in recent years. So we know that rates are highest in North America and Europe and lower in countries such as India and South Africa. And it's hypothesized that this increase in incidence over the past few years has to do with worldwide increase in risk factors for the disease. And these risk factors can include things like high and rising rates of obesity and shifts in reproductive trends that we've seen, such as having fewer children or delayed childbirth until later in life.

00:09:38:09 - 00:10:04:07
Unknown
So speaking of risk factors, looking at some additional risk factors that are listed, this was pulled off a practice bulletin from the American College of Obstetricians and Gynecologists, and it goes through the estimated relative risk for each individual risk factor for type one uterine endometrial cancers. So as you can see here, many of these factors have to do with our hormone status.

00:10:04:09 - 00:10:33:07
Unknown
So when you go down off, you know, things that we can't change like our age or, you know, our initial residency status of where we're living, things like knowledge parity, menstrual irregularities, late age of menopause, early age of menarche, use of unopposed estrogen therapy or Tamoxifen use these all relate to the fact that this type of cancer is very hormonally driven.

00:10:33:09 - 00:10:56:16
Unknown
And that also is true for obesity, which we'll talk a little bit further on today. And there are other indications, such as estrogen producing tumors that may also put women at risk for developing this type of cancer. So, for example, if there was a tumor on the ovary that secretes estrogen and rises body's estrogen levels, that may also induce this cancer to develop.

00:10:56:18 - 00:11:22:08
Unknown
There are other genetic factors as well. The most common genetic condition that's associated with development of endometrial cancer is a condition called lynch syndrome. And we won't be going too much in detail on this today. But, you know, those are things that are oftentimes outside of hormonal factors that put women at an increased risk of developing this type of cancer.

00:11:22:10 - 00:11:46:23
Unknown
So what do we know about estrogen? And let's talk a little bit about the sex steroid hormones. So estrogen is a hormone that promotes the development and maintenance of female characteristics and sexual function. There are many different types of estrogen. There are both steroidal or also known as endogenous estrogen formulations, which include things like estradiol, estrogen and Israel.

00:11:47:01 - 00:12:26:02
Unknown
And there are non-steroidal forms or exaggerated forms of these hormones, which are things like natural. EXENE Estrogens like phytoestrogens or might go estrogens. And there's also synthetic Zino estrogens that also can play a role. So as this picture further demonstrates, a woman's hormone level of estrogen changes throughout their reproductive years. And as a women starts to go through menopause, estrogen levels typically decline as the ovaries stop producing as much estrogen.

00:12:26:02 - 00:13:01:03
Unknown
And after menopause, adipose tissue or fat cells are really the primary source of estrogen produced in the body. So we know, though, that estrogen has an influence on many different sites of the body. So it can affect the brain, liver, bones, skin, heart, breasts, ovary and uterus. So not just the gynecologic organs listed in this picture. It kind of shows the effect estrogen has on all of these different organs.

00:13:01:05 - 00:13:27:01
Unknown
And I think the things to keep in mind is that we often think about the effect of estrogen predominantly on our gynecologic organs. But, you know, estradiol is the main estrogen that's produced by the ovary. But again, these estrogen receptors are found on organs throughout the entire body and as such can have an effect on all of these different organs.

00:13:27:03 - 00:13:52:11
Unknown
All right. So to discuss the role of estrogen in the development of endometrial cancer, in particular, I think it first takes that we take a step back and really understand the role of our sex hormone in just normal day to day function. And, you know, as a woman goes through their menstrual years, how these hormones play a role.

00:13:52:13 - 00:14:27:21
Unknown
So estrogen, you know, acts primarily as the hormone that allows for the endometrial lining to proliferate. And so it helps to build up the lining on the inside of the uterus. The woman's kind of hormonal levels are all about a balance between estrogen and the counterbalancing of progesterone. And so progesterone acts to help to slough off that proliferative lining of the uterus and to thin down the lining, which ultimately leads to the break down.

00:14:27:23 - 00:14:56:08
Unknown
And for menstruation to occur when women are going through their menstrual years. And so as you can imagine, if there's an imbalance between these hormones and if estrogen starts to become the predominant only hormone available to women, that lining of the uterus can get stimulated without having the secretary effects of progesterone to allow for the breakdown and release of that, such that the lining becomes thickened.

00:14:56:10 - 00:15:55:06
Unknown
And this is what we often see when women present with endometrial cancer is that they present symptomatic with post-menopausal bleeding, and that's often due to increased estrogen stores in the body that are causing the lining of the uterus to be thickened, which is leading to that abnormal bleeding to occur after menopause. So again, it goes back to, you know, balancing these two hormones of estrogen and progesterone and going about doing this is really important to maintain a healthy endometrial lining factors, you know, which increase the exposure of the uterus to unopposed estrogen, which can either be exotic Janus or endogenous like we've talked about, you know, obviously associated with increased risk of endometrial cancer.

00:15:55:08 - 00:16:35:14
Unknown
But the use of progesterone can reverse this process of both pre-cancer or cancer in the uterus, and it can protect against the development then of endometrial cancer. All right. So we know that if a woman being overweight or obese can also increase their incidence of developing endometrial cancer and case control, studies have demonstrated that there's a direct correlation where, you know, a 200 to 400% linear increase has been seen in risk of endometrial cancer in women who have a BMI greater than 25.

00:16:35:16 - 00:17:20:00
Unknown
And the reason for this is we know that adipose tissue converts astron to estradiol. So it allows for higher estrogen levels in women who maybe don't have other sources of estrogen. So, again, after menopause, once our ovaries start to decline their estrogen production, adipose cells or fat cells become the main producer of estrogen for women. In talking about the balance between these hormones, we also then know that progesterone plays a key role in helping to prevent endometrial cancer from developing and to treat endometrial cancer for some women.

00:17:20:02 - 00:17:56:17
Unknown
So these are just a few key articles, you know, that have come out over the last decade, really looking at the use of progesterone in this setting. And there are many different forms which progesterone own can be utilized, the most common of which today is probably an intrauterine device that releases progesterone locally inside the uterus. And this can be used for women who have pre-cancerous cells that are found inside the uterus to help those cells regress and to prevent the development of endometrial cancer.

00:17:56:19 - 00:18:47:11
Unknown
Progesterone can also be used as a treatment of early grade endometrial in women who maybe desire to maintain their uterus for fertility purposes, or women who may not be surgical candidates and can't undergo a hysterectomy safely due to other medical comorbidities. PROGESTERONE offers a safe alternative to treat endometrial cancer. For some women. Oftentimes when talking about how hormones affect the development of endometrial cancer, you know, a lot of women who have experienced this type of cancer are curious to learn more about the use of hormones after menopause and whether or not this is safe for women who have a history of endometrial cancer.

00:18:47:13 - 00:19:30:16
Unknown
So what we know is that systemic, unopposed caused estrogen therapy. So just estrogen therapy alone can increase the risk of endometrial cancer, and that can be up to 20 fold in some prior studies that have been done. And the increasing risk often correlates with the duration of use of hormone replacement therapy. We know that administering progesterone alongside estrogen helps to mitigate this risk by counterbalancing the effects of estrogen on the uterus and helping to maintain that nice thin lining within the uterus to help prevent the development of endometrial cancer.

00:19:30:18 - 00:19:59:12
Unknown
So when progestins are administered either in a continuous fashion or intermittently for at least ten days out of the month, or through placement of an intrauterine device that delivers progesterone, the risk of development of endometrial cancer for women that require use of hormone replacement therapy to treat menopausal symptoms is reduced to below that of a woman who is not receiving hormone therapy.

00:19:59:14 - 00:20:33:10
Unknown
Well, what about selective estrogen receptor modulators? So, you know, we've talked a lot today about how estrogen acts as an agonist in endometrial tissue, meaning that it stimulates those receptors in endometrial tissue. Tamoxifen is a type of selective estrogen receptor modulator that has been shown to significantly reduce the risk of breast cancer in breast cancer recurrence. However, its use has been associated with an increase in the incidence of endometrial cancer.

00:20:33:12 - 00:21:13:10
Unknown
So, you know, Tamoxifen is a unique drug in that it can, you know, its effects can be different between premenopausal and postmenopausal women. I think I have another slide here I'm just going to go to so I can comment on this. So in some tissues, Tamoxifen will act as what we call an agonist or it can stimulate estrogen receptors, whereas in other cells it actually can have the opposite effect and act as an antagonist where it prevents the binding and actually can not stimulate those cells and have an opposite effect.

00:21:13:12 - 00:21:45:21
Unknown
So women who are on Tamoxifen, there is an increased rate of development of endometrial cancer where it increases up to 1.6 out of a thousand patient years, and that's in contrast to about 0.2 for those not on Tamoxifen. What we know is that that risk decreases when Tamoxifen treatment is discontinued. There is also a small long term increased risk of a more rare type of uterine cancer from developing, and that's referred to as a uterine sarcoma.

00:21:45:23 - 00:22:38:11
Unknown
So the American College of Obstetricians and Gynecologists recommends that women who are on Tamoxifen undergo annual gynecologic exam and they do not recommend that in routine transvaginal ultrasound to evaluate the lining of the uterus or routine endometrial sampling be performed in women who are asymptomatic just because they're on Tamoxifen. What we've shown is that by by doing such routine screening on women, it has not been associated with increasing the detection of diagnosing endometrial cancer, but of note women shouldn't be educated when women are on Tamoxifen of this risk and of potential signs and symptoms of endometrial cancer development so that they can present to a provider should they experience any of those symptoms.

00:22:38:12 - 00:23:31:16
Unknown
And for women who do experience in particular, either abnormal uterine bleeding when they're on Tamoxifen, endometrial sampling in the form of an endometrial biopsy or dilation and cartilage, DNC procedure should be completed irrespective of the endometrial thickness on imaging. All right. So I think I got a little ahead of myself on one of the prior slides. But the other question that comes up is for women who have been diagnosed with endometrial cancer and who may be experiencing menopausal symptoms and be interested in considering hormone therapy or hormone replacement therapy following surgical management of endometrial cancer oftentimes are curious about the safety of doing so.

00:23:31:18 - 00:24:01:15
Unknown
So according to the most recent NAMS statement in menopause, you know, they state that hormone therapy may be considered following surgical treatment of early stage, low risk endometrial cancer. If nonhormonal mono options are not effective. And so what we know is that about 25% of women undergoing hysterectomy with removal of both their tubes and ovaries for endometrial cancer will be premenopausal.

00:24:01:16 - 00:24:33:21
Unknown
Traditionally, women within a mutual cancer were denied hormone therapy because of a concern that putting women on hormone therapy who have this history of endometrial cancer may be at increased risk of cancer recurrence. What has been kind of learned over time, though, and through studies is that, you know, patients with early stage endometrial cancer there really does not currently exist high quality evidence to support a detrimental effect.

00:24:33:22 - 00:25:03:17
Unknown
And so, you know, oftentimes I tell women that this decision really should be individualized. The goal of any hormone therapy should be to help mitigate menopausal symptoms, which affect a patient's quality of life. And, you know, if hormone therapy is decided upon between a provider and a patient, it should be administered at the lowest dose possible to control the symptoms and administered for the shortest duration possible as well.

00:25:03:19 - 00:25:38:22
Unknown
So, you know, in conclusion, estrogen therapy for the management of menopausal symptoms in the survivors of early stage endometrial cancers can be considered. But, you know, a patient should have thorough counseling about the risks and benefits of this type of treatment. And Nonhormonal option should be explored as part of this. And sometimes many patients will want to try those options before trying hormonal therapy to see if it results in improvement of their symptoms.

00:25:39:00 - 00:26:28:06
Unknown
There has been a increased amount of awareness of how we might use this knowledge of hormone receptor status on certain endometrial cancers and how we may utilize this to our advantage as a therapy to target for certain types of endometrial cancer. So we've talked a lot today about type one endometrial cancers, but if we look some of the Type two cancer in particular uterine serous carcinoma, which is a more high grade histology, and if you remember back to that initial kind of dichotomy of the two types of endometrial cancer in the classification system, this type two cancers tend to be more aggressive and more often will present with an a more advanced stage of disease.

00:26:28:06 - 00:26:58:02
Unknown
So we're always looking for new therapeutic targets to try to treat this disease process. What we know about uterine serous carcinoma is that it's really a very molecularly distinct entity from its counterpart of the more commonly diagnosed endometrial carcinoma. One of the things that we know about uterine serous carcinoma is that the there is dysregulation of the oncogene known as her two new.

00:26:58:04 - 00:27:33:10
Unknown
And this is an oncogene that's been very extensively studied in breast cancer prior to being looked at for gynecologic cancers. And depending on how the evaluation of a HER2 status of this type of cancer is evaluated, you know, it can be positive in about a third of patients. So in the tcga data it was found to be abnormal in about 27% of patients who had uterine serous carcinoma and therefore identified that this may be a good therapeutic target.

00:27:33:12 - 00:28:25:05
Unknown
Trust, who's a MAB, which is a monoclonal antibody often referred to by its alternative name of Herceptin, is a specific antibody that targets the her two new receptor. And we go to the next slide here, or you can see here from the initial publication in the Journal of Clinical Oncology has been now being utilized as a therapeutic target for endometrial cancer of the uterine serous subtype and has been shown to have significant improvements both in progression free survival and overall survival when used in combination with chemotherapy for advanced stage uterine serous carcinoma or recurrent uterine serous carcinoma.

00:28:25:07 - 00:29:07:13
Unknown
And so this just goes over some of the timeline of her two targeted therapies utilized in different tumor types, because we know that her to new oncogene is not unique to just uterine serous cancer, but again, was initially really evaluated in the breast cancer literature and trastuzumab was first FDA approved for breast cancer back in the 1990s and it has subsequently been looked at for gastric cancer as well as now endometrial serous carcinoma.

00:29:07:15 - 00:29:52:08
Unknown
HER2 testing is performed on endometrial serous carcinoma in a few different ways. We can test the tumor itself by doing something called immunohistochemistry. I selected this recommendation of how to go about testing the tumor because I think that this is what most U.S. oncologists today have kind of adopted in practice, which is that we test the tumor to determine the staining quality of the her two receptor status and if the score is three plus, which you can see here from a picture I included to the left here, you can see it increased staining or that brown stain be noted on the tumor.

00:29:52:10 - 00:30:32:12
Unknown
We regard those as being positive. And these are the patients that would be identified as being beneficial to consider this targeted therapy. Patients who score negative are those who have an IHT score of one or zero and those who have an equivocal score of two. We then perform additional testing, which is referred to as fish testing to determine their status, and fish testing looks a little differently by actually looking at the ratio of the her to copy number compared to the nuclei to determine the status of being positive or negative.

00:30:32:14 - 00:31:14:03
Unknown
So we can best identify which patients may benefit from this additional therapy. There is additional hormone therapy that often is considered for the treatment of endometrial cancer, specifically for the management of recurrent disease. And what we know from various studies that have been performed is that these various hormonal options often can be associated with a 20 to 30% benefit from what we see in terms of a response rate from the tumor responding to Romano management alone.

00:31:14:04 - 00:31:43:17
Unknown
And so these are just some of the different regimens and agents that have been utilized and looked at for the treatment of recurrent endometrial cancer and it lists here some of the most kind of most cited studies looking at these agents and looking at the benefit that we've gained by using a hormonal approach to treat this type of cancer.

00:31:43:19 - 00:32:17:23
Unknown
And this slide goes into just a little bit more detail here. Looking at hormone therapy and looking specifically at progestin hormone therapy and its effective rate in treating, you know, early grade endometrial cancers that are found to be estrogen and progesterone receptor positive in the various types of either progestin therapy that we use or for alternating that with something like another serum tamoxifen to have an overall effect.

00:32:18:01 - 00:32:39:06
Unknown
And this just looks at one of the more commonly cited studies looking at the trial, looking at progesterone therapy in early grade tumors, and the effect that it can have to help treat this disease. All right. I know I'm up a little quickly here and I'm just going to pause here for a few minutes to see what questions that we have.

00:32:39:06 - 00:33:06:07
Unknown
And I see a few things that have come in over the chat in the Q&A. So thank you for those people who have submitted some questions. So one of the first questions here from Fran, thank you for submitting this, Fran, is why would a woman taking an aromatase inhibitor for several years still end up with estrogen? Oops. And the question kind of canceled out there, but I'll answer it.

00:33:06:07 - 00:33:38:18
Unknown
Sorry. Estrogen receptor positive endometrial cancer. So that's a great question. So, you know, an aromatase inhibitor and I did go to in detail kind of on these agents, but our agents that block the hormone aromatase and aromatase helps to convert one form of estrogen into another to block that form of the hormone from stimulating estrogen receptors. But we have to remember that estrogen can be produced by many sources of the body.

00:33:38:18 - 00:34:03:12
Unknown
So we talk about the ovaries being a source, especially during pre-menopausal years. We talk about adipose tissue or fat cells being another source, which these aromatase inhibitors really do help to block. You know, there are other sources of estrogen as well. There are the adrenal glands, which are glands that sit on top of our kidneys that also secrete a form of estrogen that can be converted over.

00:34:03:14 - 00:34:32:11
Unknown
There are also, you know, both exogenous and endogenous form. So things within our diet that are estrogen prone, other sources that we have so aromatase inhibitors aren't a perfect blockade of all forms of estrogen. And so there still can be estrogen stimulation even when a woman is on an aromatase inhibitor, you know, which can lead to endometrial cancer.

00:34:32:13 - 00:35:06:12
Unknown
In addition to that, there are other risks to developing endometrial cancer outside of just hormonal factors. So, you know, we focused a lot of today's talk on these different hormonal factors. But there are also genetic predisposition. Like I mentioned at the beginning, things like Lynch syndrome or there's other genetic syndromes like Cowden syndrome, things that can please women, genetically add an increased risk of developing endometrial cancer that are either regardless of hormonal factors.

00:35:06:14 - 00:35:38:20
Unknown
And we also know that our type two endometrial cancers tend to also be non-hormonal stimulating so they can occur here regardless of hormonal stimulation. I'm sorry. Now, please let me interrupt. We also have some other, you know, pre submitted questions that we can go on. So if you kind of want to bounce back between those questions and the live questions, that's perfect.

00:35:38:22 - 00:36:07:08
Unknown
Okay. So thank you. So, yeah, you know, one of our submitted questions are why do this persons ask and why did they their positive for endometrial cancer and they want to know they've, they've been on it anastrozole for the past five years and still they want to know if they still have estrogen, if the body is still producing acid.

00:36:07:08 - 00:36:28:19
Unknown
And I think you may have touched a bit on that in the previous question, that might be the same person asking that question because it's a very simple, you know, kind about other one. But again, it's just that there are multiple sources of estrogen for the body. And it's not just the ovaries or fat cells, even though they're the largest producers, either premenopausal or menopausal.

00:36:28:19 - 00:36:51:13
Unknown
But there are other sources of estrogen, both that are being produced by the body and that, you know, we intake in our diet, for example. And then we have a thank you for that answer. We have another question this person is asking Does taking a topical estrogen, is that advisable at the diagnosis of uterine cancer? Yeah, that's a really great question.

00:36:51:13 - 00:37:22:15
Unknown
So topical treatments when they most often are administered, used as a form of hormone replacement therapy to treat vulvovaginal atrophy. And so what that refers to is the effects that we have as women when our estrogen levels decline on the inside of the vagina and kind of on the outside or around the urogenital or urinary stream in our output from our urinary tract.

00:37:22:17 - 00:37:55:08
Unknown
So women who experience vaginal dryness, you know, dryness with intercourse after having their ovaries removed or just becoming menopausal, you know, may be more interested in using topical estrogen to treat those symptoms. Then systemic estrogen therapy, which is primarily utilized when women are having more widespread menopausal symptoms, things like hot flushes, night sweats, things that aren't just as local as vulvovaginal atrophy.

00:37:55:10 - 00:38:28:19
Unknown
The the main benefit of utilizing more local therapy with vaginal estrogen is that it is not often absorbed at a high rate, and there's very little systemic absorption. So it's thought to be kind of less risky than utilizing systemic or kind of oral or a pill form of hormone therapy. And so, you know, I go back to those slides when I talked about we don't have great data looking at, you know, how safe is it to use.

00:38:28:19 - 00:39:05:14
Unknown
But when we look at some of these retrospective studies and we evaluate the data that we do have on women who have used hormone therapy both as vaginal estrogen, as well as oral systemic therapy, it has been thought to be safe in women as long as they have in early stage disease. That's a low grade. There really is insufficient data to evaluate the safety of this for women who have higher stage disease or who have higher grade, you know, endometrial carcinoma.

00:39:05:14 - 00:39:37:00
Unknown
But it is, I think, pretty universally felt to be safe and even the vaginal estrogen more safe than systemic options due to its low absorption rate. Appreciate it. Can I just bring up you know, I think I highlighted this when we talked about it, but the recommendation truly is to utilize any of these additional of hormone therapy. You know, we want women to have relief of their symptoms and improvement in their quality of life, especially after they have decline these hormones when their ovaries are removed surgically, for example.

00:39:37:02 - 00:40:03:09
Unknown
But, you know, it is still recommended that women utilize these therapies for the shortest duration of time possible and at the lowest dose that really helps to control those symptoms. Appreciate that answer. This is a another live submitted question and this person wants to know is taking a progesterone therapy ever introduced to postmenopausal patients? Okay, that's a great question.

00:40:03:09 - 00:40:36:16
Unknown
So when women and I want to make sure I understand this correctly, when women go on hormone replacement therapy, let's say a woman is going on this therapy not because they've had surgery and had their ovaries removed, which may be what some women here, you know, are undergoing symptoms from if they've been treated for endometrial cancer. But let's say a woman does not have a history of endometrial cancer and is going through natural menopause, where they start experiencing symptomatic menopausal symptoms like hot flashes and night sweats.

00:40:36:18 - 00:41:09:22
Unknown
Those women, they go on systemic meaning like an oral pill for hormone replacement therapy if the uterus is still in place, should always be given both estrogen and progesterone if they're post-menopausal. And that goes back to the slide that we know. If we give estrogen alone, estrogen stimulates that lining of the uterus. And by not having that counterbalanced by progesterone can increase a woman's risk if they're not on progesterone therapy of developing endometrial cancer.

00:41:10:00 - 00:41:44:23
Unknown
So it's absolutely recommended for women who have a uterus who are going on symptomatic management or treatment of menopausal symptoms that they be placed on both hormones, and that can be administered in a variety of fashions, either continuously as a daily pill. It can be administered for like a withdrawal bleed for a portion of the time, as long as it's greater than ten days in the monthly cycle, or it can be administered in the form of placement of an entry uterine device so they can have continuous progesterone released in that fashion.

00:41:45:01 - 00:42:23:17
Unknown
Now, if a woman has undergone a hysterectomy and had their uterus removed, whether or not their ovaries were removed or not, and they are symptomatic from menopause, they only need estrogen typically as hormone replacement therapy, because the role of progesterone is really to counterbalance the estrogen and safeguard the endometrium within the uterus. So if they don't have a uterus, that risk of development of endometrial cancer is not present and progesterone is not required as part of their hormone regimen.

00:42:23:19 - 00:43:00:10
Unknown
Thank you. So this next question again, as you know, Chris, a minute to minute question and this person asked, is there an over-the counter exaggerated slash test that is that is cost effective and easy to use? You know, I'm not familiar with any over-the-counter test that look specifically at that. That does not mean that they don't exist. It's just not something that I typically recommend to patients or that or that I have really encountered in my clinical practice.

00:43:00:12 - 00:43:28:08
Unknown
There are some blood tests that I will sometimes offer patients. And again, this doesn't mean that they're not available over the counter. I just can't really speak to the the testing, you know, the internal validity of any of those tests, not being familiar with them. There are some blood tests that can look at, you know, hormone levels fluctuate, especially before menopause quite drastically in a woman.

00:43:28:10 - 00:43:56:21
Unknown
And so typically when we're testing a woman before menopause to look at the hormone levels, we look a step above or before estrogen levels by looking at the hormone levels of LH and FC edge, which are hormones that are actually secreted by the brain, by what's called the pituitary gland. And these are the hormones that then go down and travel through our bloodstream to our ovaries to get our ovaries to secrete estrogen.

00:43:56:23 - 00:44:24:09
Unknown
And so we look at the levels actually of the brain hormones in addition to estrogen levels, to determine if a woman is, in fact, menopausal from a hormonal perspective, sometimes. So those blood tests can be easily drawn. But again, for women who are, you know, before menopause, those level hormones can all drastically vary depending on which time in their cycle they are currently on.

00:44:24:09 - 00:44:56:16
Unknown
When the test is drawn, you and this next question this person is asking, well, they are in surgical menopause and it and it's being treated with HRT and they want to know does adding a possession and past us? Testosterone. Testosterone. I'm sorry sashes and does it decrease your chances of recurrence? So just making sure that I understand this.

00:44:56:16 - 00:45:26:04
Unknown
So if someone has a history of endometrial cancer and they undergo surgery to treat endometrial cancer, and if they have an early stage, early gray disease, maybe a provider has talked to them about going on hormone therapy. And again, you know, I think our data that we currently have is that we should counsel patients on the risks and benefit of this, which, you know, look into other risk factors that we think about with hormone therapy use and making sure women don't have other medical comorbidities that may put them at risk by on this therapy.

00:45:26:06 - 00:46:04:01
Unknown
Typically, we administer estrogen alone in this setting because, again, the role of progesterone is really predominantly as a safeguard to the endometrial lining in the uterus. The, you know, the historic thought that estrogen could stimulate recurrence of disease is based on a premise that there are actual cancer cells that are would be present. And so, you know, with somebody who has a very early stage, early grade disease, the thought is that surgically all cancer cells really should be removed at that time.

00:46:04:01 - 00:46:28:10
Unknown
And that's why we think it's safe to put women on estrogen. So, you know, the thought of adding back progesterone to counterbalance that, you know, I don't think there's anything that should be being stimulated if we're having good selection of patients and counseling patients on who's going on estrogen therapy, you know, do we sometimes utilize progesterone in instances if we're putting someone on estrogen?

00:46:28:12 - 00:46:49:03
Unknown
You know, one example I can think of in my clinical practice is some women who have things like endometriosis, which is a process when cells that should be normally on the inner lining of the uterus get outside of the uterus and can, you know, implant on any of the gynecologic organs or really anywhere in the abdomen or pelvis.

00:46:49:05 - 00:47:11:05
Unknown
And those endometrial implants can continue to be stimulated by estrogen. So sometimes having those women on progesterone as well can help to counterbalance the effect of their of estrogen. But I would not typically put a woman if I'm deciding to start hormone therapy because she and she has a history of individual cancer, I do not routinely put them also on progesterone.

00:47:11:05 - 00:47:52:11
Unknown
I just start them on on estrogen alone. Appreciate that. So now this for this next question. This person would like to know, does estrogen play a role if you've started getting your period of period at an early age or going into, you know, menopause at a later age. Yeah, absolutely. So both, you know, the age that you start menstruating, the age that you stop menstruating, those are indicative of higher levels of hormones being produced by the ovary.

00:47:52:11 - 00:48:14:13
Unknown
So, you know, before we start menstruating, our hormonal levels are very low in prepubescent girls. And as the ovaries start to produce estrogen and stimulate that lining, that's what starts our menstrual cycles to occur. So it suggests that higher levels of estrogen are present at an earlier age. If you start menstruating at an earlier age, same thing goes with menopause.

00:48:14:15 - 00:48:41:18
Unknown
For women who may undergo premature ovarian failure or decline in their hormones at an earlier age. You know, we know the average age to go through menopause for most women is around 5051. But there's a big variety in that. And some of that can be genetic. But for women who menstruate longer past 5051, that means they have higher levels of estrogen being secreted by their ovaries to a later age.

00:48:41:20 - 00:49:06:08
Unknown
Other things that can also factor in that is pregnancy. So, you know, both the amount of times a woman becomes pregnant because we have hormonal fluctuations during that time and less of a rise and fall as we don't menstruate during those months. And same with, you know, during the months of breastfeeding as hormone levels can also stay low.

00:49:06:09 - 00:49:52:08
Unknown
So for this next question, this person is asking intake and birth control increase your chances of being diagnosed uterine cancer. Okay, that's a great question. So most birth control is administered in a combined fashion. So the most common type of birth control that's given is estrogen and progesterone. So because of that counterbalancing use of progesterone therapy and birth control, it's actually thought to be protective towards the development of endometrial cancer because it causes women to often have a monthly withdrawal bleed or menstrual cycle that cleans out that lining and doesn't allow for the overgrowth of that endometrium that can lead to pre-cancerous conditions and cancer.

00:49:52:10 - 00:50:34:14
Unknown
So it is not thought to be associated with development for that reason, because it's normally both hormones together again. So this next question is related to diet. This person will like to know are there any estrogen related foods that someone who has post hysterectomy and any and who is and and post menopause should avoid? Yeah, that's a great question because you know that exogenous estrogen and one of the major sources of how we get that is through dietary intake.

00:50:34:16 - 00:51:02:16
Unknown
So, you know, just some thoughts on that. You know, I always tell patients the most important thing is a well-balanced diet. And most women who really eat a well-balanced diet aren't going to be eating foods that really are very, very high in estrogen. Classically, foods that are considered to have high estrogen levels include things like soy, soybean products or any you know, high soy things like flax seeds.

00:51:02:18 - 00:51:39:16
Unknown
There's different nuts and chickpeas, some beans and all these natural food sources. And then there's also supplements that are known to also contain more phytoestrogens or naturally occurring estrogen aids that can also raise estrogen levels. So just making sure that, you know, if you're someone who buys products over the counter, making sure you have an understanding of what's in those products that you're taking and that you're not taking something that maybe is unregulated or unsafe in that regard.

00:51:39:18 - 00:52:16:15
Unknown
So for this next question, I this person is asking this person is diagnosed with an early stage type one diagnosis, and they would like to know what would the effects of being a mega stroke have on their diagnosis as treatment. Okay, so go back. You said it was a type one early stage endometrial cancer, and they're curious about the effects of progesterone.

00:52:16:17 - 00:52:53:04
Unknown
So, you know, many women who desire future fertility would be treated with progesterone therapy. So, you know, we need to make sure that women are a safe candidate for that. And I don't know if this is the way that this person is asking this question, but, you know, we want to make sure first that the grading of that tumor, it's an early grade tumor and you know, it classically should be really looked at in a fashion that's not just an individual biopsy in the clinic, but done in a more systemic fashion with the DNC procedure to evaluate the grading of the tumor.

00:52:53:06 - 00:53:17:13
Unknown
Oftentimes in these women who want to undergo fertility sparing treatment of early grade individual cancer, I have them do an MRI to evaluate if there is an actual lesion that's seen or a masked up seen inside the lining of the uterus. And the best candidates are really those that that lesion are masked as not invade into the muscle layer called the Miami trim of the uterus.

00:53:17:14 - 00:53:50:17
Unknown
Obviously, candidates are best for those who desire future fertility and who don't have other medical co-morbidities that may prevent them from having a safe pregnancy. And oftentimes, if we treat them with progesterone own, we treat them with an intrauterine device, an IUD that secretes progesterone, because in various studies that have looked at the various treatment modality uses of oral progesterone versus an intrauterine device, we do see higher response rates when it's administered as an intrauterine device.

00:53:50:17 - 00:54:13:17
Unknown
And some of that is patient compliance. It's not something you have to remember to take on a daily basis. Some of that is also that with oral progesterone, you know, there are different side effects to the way that we administer progesterone. And one of the side effects of high doses of oral progesterone that we use to treat individual cancer is actually weight gain.

00:54:13:19 - 00:54:36:19
Unknown
And so as we've talked about with the Association of Individual Cancer, with many women being overweight or obese with this diagnosis, we don't want to be putting them on an agent that could further exacerbate that risk factor for individual cancers. So sometimes going on an IUD, which doesn't carry that same risk of weight gain, can really be a better treatment option for many patients.

00:54:36:19 - 00:55:09:20
Unknown
I have found. Thank you. So this next question is a lot of questions and this person is asking how successful is enhertu for high grade serious cancers that are HER2 positive? Yeah, so that's a great question. So it depends based on the studies, if it's been so, you know what has been shown. Initially they looked at transduced by percept in just as a treatment in itself and we didn't really see it being very effective.

00:55:09:20 - 00:55:52:22
Unknown
So we went back to the drawing board and then we administered Herceptin for patients who have advanced stage of stage three or four disease, meaning it's traveled to the lymph nodes or to other locations outside of the pelvis, into the abdominal cavity or beyond. And we looked at utilizing that in the upfront setting with chemotherapy. And that's where we started to really see a larger benefit in both the disease, not recurrence, a progression free survival and overall survival when it was administered as the primary adjuvant treatment after surgery we also have looked at utilizing this agent for recurrent cancer.

00:55:52:22 - 00:56:20:21
Unknown
So women also qualified for the study if they had recurrent uterine serous cancer where it also showed a similar benefit. So right now we're starting to kind of re explore the options since we've seen such improvement, we started to look at women who maybe can also utilize this treatment for earlier stage disease to see if it has similar improvements in their progression free survival and overall survival.

00:56:20:21 - 00:56:43:18
Unknown
And that study has kind of been under, you know, enrolling currently. But right now we're just utilizing it for higher stage disease initially or for recurrent disease. And again, about a third of women who have uterine serous carcinoma will be found to have her to positivity. And of those who are found to be HER2. Again, this is a targeted therapy.

00:56:43:18 - 00:57:16:11
Unknown
So that means that you know we're really improve in our ability to treat cancer by learning the individual nuances of a patient's cancer and what their cells respond to. So we know that if they have this HER2 positivity by either the immunohistochemistry or the fish testing, that they likely will have a very high response rate to trastuzumab when given in combination with chemotherapy and I really appreciate that answer.

00:57:16:13 - 00:57:48:17
Unknown
I think we have time for one more question and that question is how does the hormonal treatment like progesterone that is sometimes used for early stage uterine cancer impact, weight gain and change in a change in menstrual cycle? Yeah. So again, it depends on how it is being administered. So progesterone can be given as an oral pill. It can be given and administered locally in the form of an intrauterine device.

00:57:48:18 - 00:58:13:10
Unknown
The oral formulation is going to have a higher systemic absorption, meaning that in order for your body to process the hormone in that oral pill, your intestinal tract needs to absorb that medication. It needs to get into your bloodstream to have an effect down on the uterus. So by having a higher systemic absorption of that protein, of that hormone excuse me, it can lead to more side effects such as weight gain.

00:58:13:12 - 00:58:42:00
Unknown
When you administer out it is that is an intrauterine device. It has a much lower systemic absorption such that some women who have a marina IUD and still continue to ovulate, meaning the progesterone doesn't even stop their oblation. It really is just acting locally on that endometrial lining. And so as such, because there is such a low, if any, systemic absorption, women don't tend to have that side effect of weight gain when it's administered in the form of an IUD.

00:58:42:02 - 00:59:01:11
Unknown
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00:59:01:11 - 00:59:22:21
Unknown
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