Chapters Transcript Video Hormone Replacement Therapy in Cancer Survivors Mm. Mhm. Hello. My name is Melissa Moffett. I am a g y, an oncologist at Roswell Park, and I'm going to talk today about hormone replacement therapy in cancer survivors. This is a CMI lecture, and it's targeted at primary care physicians, gynecologists and oncologists. We're going to be talking about estrogen and progesterone use and female cancer survivors in providers. Here's my contact information. If you need it, I'd like to, um, thank Ashley Snowden, Daniel Fleischmann, Samantha Gordon and Aimee Sisson for helping with the slides. Medic has a disclosure policy, and I have no disclosures to make learning objectives for this lecture are that upon completion of the lecture, you should be familiar with the literature for hormone replacement use in women, Um, including cancer survivors and those with hereditary breast ovarian cancer syndromes. Here's the outline for the lecture. First, I'm going to define who survivors and provide Ivers are in the United States, and then we're going to review literature and guidelines for hormone replacement therapy. Improve Ivers, breast cancer survivors, lung cancer survivors, colon cancer survivors, ovarian cancer survivors and cervical cancer survivors. So who is a cancer survivor when we look at the cancer statistics, we can see that breast cancer has a much higher incidence than the rest of the cancers for women in the United States. And its maybe on a little bit of an uptick here. When we compare the instance of the top 10 cancers for women in the United States against the estimated number of deaths from the top 10 cancers women get in the United States, we again see breast is the most common cancer for women, then comes along then colon and then uterus. The cancers that women are dying from most often are lung, and then breast, colon and uterus is down the line there. Before we get to uterus, we passed aggressive cancers like pancreas and ovary, so this leaves us with many breast cancer survivors, many colon cancer survivors, some lung cancer survivors and many uterine cancer survivors. We've been very fortunate that since 1990 we have decreased the chance of you dying from cancer in the United States by 25% which leads us to having more and more cancer survivors every year. This table here, this graph here shows, um, the number of deaths that have been averted that would have been expected had we just had the same treatments we had in the nineties. And if we look at this graph, what we see is that we're having a lot more older and older cancer survivors. Now, during this talk today, we're gonna be talking about women who are in the light blue and light purple. Part of this graph women who are 55 younger. For the most part, this is Gilda Radner. Some of you may know who she is. She was a Saturday Night Live comedian and she developed ovarian cancer in the eighties. We had not yet found the Bracha mutation when she was, uh, sick and got diagnosed. She, um, went from doctor to doctor saying something's wrong and everybody in my family has had ovarian cancer. But it took a number of months for her to get diagnosed as ovarian cancer is a challenging diagnosis to make. She underwent similar treatments to what we do now, and she went into remission. She had a remission that was, um, average in length 1 to 2 years. During that time, she wrote this book. Interestingly, though, um, Gilda Radner was likely a pre Viber as well as a cancer survivor, meaning that that family that strong, strong family history of ovarian cancer was likely a Bracha mutation after Gilda Radner's death. Um, Gene Wilder, her husband, wrote this book with one of her physicians about her family history and her diagnosis and treatment, and the Gilda Radner's family history and her story, as well as Gene Wilder's fundraising, went on to create the Gilda Radner from Familial Ovarian Cancer Registry um, at Roswell Park. And those familial cancer registries went on to be how we developed or learned about the Bracha mutations. So women who have a Bracha one mutation have a 55 to 65% chance of developing breast cancer by the time they're 70. And women with the BRCA two mutation have a 45% chance of developing breast cancer by the time they're 70. And that's as compared to those with wild type Gracchus, who have a 12% chance of developing breast cancer by the time they're 70. This is Angelina Jolie. She has a Bracha one mutation, she wrote about her experience being a patient and undergoing risk reducing surgeries. Um, in the new York Times in in May of 2013, she underwent both risk reducing mastectomies and risk reducing bilateral sopping over ectomy. Lynch syndrome is another familial predisposition to developing cancer, another genetic predisposition to developing cancer that involves multiple genes. And each gene has a different risk for the different cancers. But in General, Lynch Syndrome gives women an 80% chance of developing colon cancer by the time they're 70 60% chance of developing uterine cancer by the time they're 70 and a 15% chance of developing ovarian cancer by the time they're 70. Lynch syndrome is rare, so one in every 370 women have it, and it's even uncommon in people with colon cancer. Only one and 35 people with colon cancer have lynch syndrome. Nonetheless, people with Lynch Syndrome Bracha one mutations bracket, two mutations. And now we have a whole list of other genetic mutations that lead to, uh, having a predisposition of developing cancer such as brick one p 10 tp 53 pal b et cetera. So those are our pre vipers. Many providers who have an increased risk of developing ovarian cancer due to their genetic mutation are recommended to undergo a risk reducing bilateral scalping oo for ectomy, the age at which they are recommended to undergo. That surgery depends on how high their risk of developing ovarian cancer is, as well as when people develop ovarian cancer that have that genetic mutation. It's generally 35 to 55 so some women who have risk reducing bilateral subpoena offer economies will be put into I a transgenic menopause from the surgery. Some women undergo the surgery later at 15 55 and those women may have already gone through natural menopause. This surgery can reduce the risk of developing ovarian cancer down to near baseline. It reduces their all cause mortality. And there are some sort. Some studies which show that taking the tubes and ovaries out also reduces the risk of developing breast cancer for those who have a hereditary breast, ovarian cancer syndrome. And what we want to remember with these providers is that our goal is really to be prolonging their life in decreasing the risk of developing a life shortening malignancy. So when we do put women into I a transgenic menopause by taking out the fallopian tubes and ovaries prior to when they were going to go into menopause. Average age of menopause is 52. We know that, um, those women, if they're if they're hormone replacement therapy, isn't started that they haven't increased all cause mortality. So women whose tubes and ovaries are removed prior to natural menopause die earlier. They also have increased risk of developing osteoporosis to slip anemia, atherosclerosis, cardiovascular disease and dementia. The symptoms of surgical menopause are worse than those of natural menopause. Replacing those hormones, particularly estrogen, can prolong life, and it can nearly resolve the other increased health risks. And it definitely can increase the patient's quality of life. So I'm going to start talking about the evidence, the literature about hormone replacement. And before I do that, I just want to say two things. One is when I say hormone replacement therapy. That means replacement of the estrogen only if the uterus in the patient has been removed. If the uterus is in sight to then that means replacement about the estrogen and progesterone. Progesterone is added into hormone replacement, only to minimize the risk of uterine cancer that comes along with unopposed estrogen. The other thing I want to say is in reviewing the literature around hormone replacement therapy, many different estrogens are used. I'm going to not go into the different estrogen's. We're just going to talk about the results of each study. So in the Women's Health Initiative, we looked at 27,347 women between the age of 50 to 79 we looked at, um, giving women estrogen versus placebo and following them for a number of years and women who had uteruses inside to we gave them estrogen and progesterone versus placebo. So what we found in the Women's Health Initiative is that replacing hormones really had some increased risks. We increased the risks of women developing congestive heart disease, Venus dumbo embolism and breast cancer. On the other hand, there were also some benefits of having hormone replacements, such as women who had estrogen and progesterone replaced, how to decrease risk of developing colon cancer, and they had decreased all cause mortality. But as you recall, we, uh for the most part stopped prescribing hormone replacement therapy for women based on these increased risk of of heart disease and thrombosis embolism. So since that study, There have been, um, re visitations to the study population. So 18 years later, when we look back at those women, what we find is that those women who had their estrogen replaced for seven years and estrogen and progesterone for five years they actually had no increased cancer mortality. Nor did they have any increased all cause mortality. And in fact, when we look at just the younger women, so as we recall, the Women's Health initiative included women that were up to 79 years of age. When we look at just the younger women women 50 to 59 those women who are around the age of peri menopause there were 8700 women, including included in wh I who were that young and when we follow them out 18 years. What we found unexpectedly is that estrogen actually reduce the risk of developing breast cancer and reduce the risk of congestive heart disease and overall mortality. On the other hand, estrogen plus progesterone is what was found to increase the risk of breast cancer. So the young women, 50 to 59 had no increased cancer, mortality or all cause mortality when their hormones had been replaced. That's important. So due to that, we now think it's really quite safe to be giving hormone replacement therapy to women in their early fifties. So going back to talking about providers providers who undergo a risk reducing bilateral scalping oo for ectomy, there are studies that show taking out the tubes and ovaries decrease those women's chances of developing breast cancer. In addition to that, we have multiple observational studies that show that then if you give them back their hormones estrogen and progesterone if needed, that it does not change the fact that their risk of developing breast cancer was reduced by having their tubes and ovaries removed. So let's look at what the national guidelines are for replacing hormones in our pre vie vers, many of whom are put into I a transgenic menopause by having their tubes and ovaries removed at prior to menopause. Nan's is the North American menopause society, and what they say is that hormone replacement therapy does not increase, does not increase the risk of breast cancer in women with a family history of breast cancer or a genetic predisposition to developing breast cancer and the N. C. C N they say we need to use caution in giving hormone replacement therapy to women who have, um, these genetic mutations after the tubes and ovaries have been removed. An ACOG, the American College of Obstetrics and Gynecology. Their recommendations regarding providers is that hormone replacement therapy is the most effective therapy for Visa motor symptoms or hot flashes. However, there is some literature that suggests an increased risk of breast cancer and venous thrombosis embolism. So individualized care. Consider non hormonal options, but definitely use local topical estrogen if the problem is not, um, Visa motor symptoms, but instead, genital urinary syndrome of menopause. Um, in other words, a, uh, a trophic or dry vagina. So when we put all this together, what I would say is that if you have a young woman who has had her tubes and ovaries removed and she's in I a transgenic menopause or even in her fifties, maybe up to 55 went through natural menopause but is suffering from, um, menopausal symptoms like hot flashes. And she had a genetic disposition to developing ovarian and breast cancer that you should go ahead and treat her with hormone replacement as needed and then continue it up to around the time of menopause or a few years afterwards. We're going to go on and talk about hormone replacement for, um, the guidelines for hormone replacement therapy for women who actually had breast cancer as opposed to just the Previ Ivers. So ACOG says essentially the same thing. Individualized care. Consider non hormonal options and that given conflicting evidence on safety of hormonal replacement therapy and women with breast cancer. Um, if you have a patient who's got hormone positive breast cancer to be using non hormonal options, you also could consider non hormonal treatment for genital urinary syndrome of menopause. Um, for women who have an estrogen receptor positive breast cancer, however, short term use of local estrogen is also okay if you try those other methods and they fail. And what does Nam say? They say if you have a breast cancer survivor, hormone replacement therapy is generally not advised and that there are observational studies that report both neutral effects and increased risks of breast cancer recurrence, but that local estrogen treatment can be used for genital urinary syndrome of menopause, and N. C. C N says hormone replacement therapy is the most effective treatment for the symptoms of menopause, but is contra indicated in patients who have hormonally dependent cancers and to use non hormonal options that you could consider using hormone replacement after consideration of the risks and benefits, and that you can individualize care. So let's review the literature and breast cancer. So Dr Spear off the noted reproductive endocrinologist, says hormone replacement therapy increases the risk of breast cancer. This was in 2000 and eight. And he said that, uh, those women whose breast cancer, um, is associated with hormone replacement therapy tends to be earlier stage and lower grade with improved survival rates, and that those risks returned to baseline after discontinuation of hormone replacement therapy, suggesting that not only do we need to be looking at the statistics from the studies but also putting it into context about what what those cancers actually look like. So hormone replacement therapy after breast cancer diagnosis leads to lower mortality in multiple large observation. All studies as listed here when we're looking at our prospective studies. The Stockholm Trial, a study of 378 women with a history of breast cancer. They were put on hormone replacement therapy versus placebo and followed for 10 years. And in this study there was no difference in recurrence and there was no difference in mortality noted in the habit trial. The hormone replacement After breast cancer trial, Another prospective randomized trial. 442 women with a history of breast cancer were included, and they were given hormone replacement versus placebo. And they did find an increased risk of recurrent in the hormone replacement therapy arm. But there was no difference in mortality. So putting it all together about breast cancer can you use hormone replacement therapy and young women with symptoms of menopause? I think that you can, However, um, it's probably safest to go ahead and try our non hormonal options first. We actually have a number of non hormonal options that can be beneficial with hot flashes. And then if you fail these non hormonal options and your patients suffering and you really think that she is going to benefit from using estrogen or estrogen and progesterone, if the uterus is still in place, that you should consult with her oncologist in making that decision, but that it is actually quite reasonable to go ahead and try it. Now, lung cancer is a little bit different. So surgical menopause taking out the tubes and ovaries earlier than menopause increases your risk of developing lung cancer and going into menopause earlier. The unusual also increases your risk of lung cancer. There's also a synergistic effect between smoking and hormone replacement therapy. We don't usually think of lung cancer as being one of the hormonally dependent cancers, but in fact, um, in two studies, hormone replacement therapy is shown to decrease survival in patients with lung cancer, particularly those who are older and who smoke or have a history of smoking. There are two other studies that show that there's no difference in outcomes noted. Because of these interactions between hormones and lung cancer, they have looked at anti estrogen endocrine therapy for treatment, and it has shown no clinical benefit. So when you put all that together for lung cancer, I would hesitate to be using um, hormone replacement therapy for women with lung cancer or a history of lung cancer. I would do my best to be trialing them on non hormonal options and only go to using hormone replacement if they are truly suffering and you've tried everything else and you've consulted with her oncologist. Colon cancer is still another very different story than breast and lung, because hormone replacement therapy decreases the risk of developing colon cancer. As we saw in the wh. I study and hormone replacement therapy also decreases your risk of dying from colon cancer. Since the evidence is all positive in colon cancer survivors and giving them hormone replacement therapy, we should be considering placing young women who are put into cryogenic menopause due to their colon cancer treatment on systemic hormone replacement therapy. Endometrial cancer, like breast cancer, is one of our hormonally dependent cancers, and we know that estrogen unopposed increases your risk of developing endometrial cancer. And we saw in the wh i that if you're given estrogen and progesterone continuously, that that can decrease your risk of developing endometrial cancer. We have one randomized controlled trial and endometrial cancer, looking at hormone replacement therapy versus placebo in 1200 women with early stage endometrial cancer. This study was closed earlier due to the results of um, the wh I study. What we know from this trial was that there was a low recurrence rate in both the patients who had hormone replacement therapy and those who did not. There are a few meta analysis of, um, observational studies, and what we see from them are that there's. There appears to be no increased risk of recurrence in endometrial cancer patients who are given hormone replacement therapy. So when you have young women who are endometrial cancer survivors and our, um, suffering from symptoms systemic symptoms of menopause, we generally would try using non hormonal treatments on them prior to going to, uh, hormone replacement, but that it is reasonable to give them hormone replacement after they've failed non hormone, non hormonal options. So ovarian cancer It's not a common cancer, but it is a cancer that younger women get, and they're put into I a transgenic menopause because of it. So the wh. I showed that putting women on hormone replacement therapy did not increase the risk for developing ovarian cancer. However, there is a meta analysis of 52 studies that found an increased risk of developing ovarian cancer because of hormone replacement therapy. And when we look at giving hormone replacement therapy to women who are ovarian cancer survivors, what we find is that there's no change in their prognosis or that they have an increased improved survival and that they have improved quality of life. So for randomized controlled trials, this study looked at 100 and 39 women with ovarian cancer who were diagnosed prior to the age of 59. And they were given hormone replacement therapy or placebo, starting six weeks post up and followed for two years. And for them there was no impact on length of remission or overall survival. And in this meta analysis of 419 ovarian cancer survivors who used hormone replacement therapy versus non users, we see that hormone replacement does not impact prognosis but that it does improve quality of life. Some ovarian cancers are not very aggressive, and they're referred to as low malignant potential tumors. These are rarer than our usual high grade, very aggressive ovarian cancers, but they tend to occur in younger women. And again, um, maybe the reason for I a transgenic menopause. So what we know about low malignant potential tumors of the ovary and hormone replacement therapy is a hormone replacement therapy. Before or after the diagnosis had no impact on overall survival. It is very reasonable to be giving hormone replacement therapy to women who have the usual high grade serious ovarian cancer. Also, women who have low malignant potential tumors of the ovary. And there are some other types of ovarian cancer, such as malignant germ cell tumors that, um, occur in very young women, teenagers and girls. Those women should also be given hormone replacement therapy in order to treat their, uh, systemic symptoms of menopause. There are some types of ovarian cancer that are more hormonally dependent than the usual type that we just discussed. And so, uh, and these are These are rare types of ovarian cancer. So if you're considering putting somebody with a history of ovarian cancer on hormone replacement, it's, uh, reasonable to review the histology or talk to their g Y an oncologist or oncologist. Because, um, we would think of low grade serious carcinoma is being estrogen dependent, same with endometrium, right and potentially clear self where we would be trying non hormonal treatments first, in order to see if we could use them to, um, resolve those systemic symptoms of menopause. Cervical cancer is a cancer of young women. 70% of women with cervical cancer are diagnosed prior to the age of 55. Many of these women are put into menopause because of their treatment. There is some evidence that suggests that estrogen may be associated with an increased risk of cervical adenocarcinoma when we look at randomized controlled trials. This study of 120 women who had cervical cancer and were younger than 45 80 of them received hormone replacement therapy and 40 had placebo. And what we saw was no difference in recurrence rates and no difference in survival rates, since cervical cancer patients tend to be very young compared to the rest of our cancer patients, Um, if they are suffering from symptoms of systemic menopause, we should be placing them on hormone replacement therapy and continuing it to the normal age of menopause, or a few years after we know that alcohol increases the risk of breast cancer recurrence. I think it's interesting that we don't fear alcohol and our breast cancer patients the way we do estrogen, and when I think about it, it's got to be because it's a quality of life issue that we don't want to tell our breast cancer patients that they can't have a glass of wine on the weekends or you know, at their daughter's wedding. And I think we should consider estrogen to be similar in terms of increasing quality of life. So young women who are suffering from lack of estrogen their quality of life is greatly impacted. So physicians are hesitant to prescribe hormone replacement therapy since wh I came out. And there are times and reasons when hormone replacement therapy is reasonable and or even recommended. And so, as we talked about with ovarian cancer patients, those patients, by and large, are great candidates for hormone hormone replacement therapy. And so when we looked at Swedish gynecologists and their patients in the young patients with ovarian cancer, what we found was that only 63% of Swedish gynecologist would prescribe hormone replacement therapy to those patients, whereas 92% of green oncologists would have offered it. So we're shy of prescribing hormone replacement therapy and so just going over our key points, there is very little evidence that hormone replacement therapy is harmful to cancer survivors. There's actually quite a bit of evidence that hormone replacement therapy is helpful in cancer survivors and provide Ivers. We always think, do no harm. And thus if we're worried about the risks of hormone replacement, we think I'm not going to prescribe it. That's doing no harm. Uh, sometimes not. Prescribing hormone replacement therapy can actually be doing the harm if we're keeping in mind the, uh, increased risk of all cause mortality associated with early menopause and some of the other studies we talked about. So in conclusion, I would recommend that we focus on the patient as a whole with our goals being helping them have a healthy long life with a good quality of life. Don't hesitate to contact me if you have any questions. My email address was at the beginning of the slides, and here is the contact information to receive your CMI credit. Thank you. Created by
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