The Dr Louise Newson Podcast - 126 - What does the evidence say about breast cancer and HRT? With Professor Isaac Manyonda

Episode Date: November 16, 2021

Professor Isaac Manyonda is back by popular demand to discuss perhaps the most important issue for women considering and taking HRT; what is the risk of breast cancer if I take HRT? Professor Manyonda expertly takes the listeners through the different issues, one by one, including comparing the level of risks of breast cancer from HRT with lifestyle factors such as weight and alcohol intake. He outlines the risks according to different types of estrogen and progesterone, and explains the difference between estrogen receptor positive and negative breast cancers. This episode is a must-listen for anyone who wants to be able understand – and clearly explain to others – the evidence-based picture around breast cancer and HRT, for both healthcare professionals and anyone interested in the topic. Prof. Manyonda’s 3 take-home messages: The strong evidence shows that estrogen does not increase the risk of breast cancer and it could even have a protective effect. If you take estrogen and develop breast cancer you have a lower risk of dying from the cancer than women not taking estrogen. The benefits of HRT extend way beyond the improvement of your symptoms and include protection of the cardiovascular system, your bone health, your immune system, and potentially prevention of dementia.

Hello, I'm Dr Louise Newsome and welcome to my podcast. I'm a GP and menopause specialist and I run the Newsome Health Menopause and well-being centre here in Stratford-Bron-Avon. I'm also the founder of the Menopause charity and the menopause support app called Balance. On the podcast, I will be joined each week by an exciting guest to help provide evidence-based information and advice about both the perimenopause and the menopause. So today, by popular request, I have back with me, Professor Isaac Moniando, who is very inspirational, incredibly clever and very kind to give up his time yet again for the podcast. And today we thought we would talk about

breast cancer and HRT, because this comes up all the time. This is the main reason why women are often scared of taking HART and also healthcare professionals are scared of prescribing it. So welcome again, Isaac, and thank you for joining me. Thank you, Leris. Thank you. I do think this is one of the especially important topics for us to discuss because it's probably one of the reasons or the most important and the most common reason why women either choose not to take HRT or come off of it. And there's a lot of information out there that is either completely wrong or very misleading or certainly very frightening to a lot of women. I think it is important to try and put things into perspective and address the

issue of whether HRT may say increases the risk of breast cancer or not. And it is probably the biggest reason I think some people are worried about other things, but it is the biggest reason that people are worried. and the reason that people often refuse to be given HART. Now, if we just start at the beginning, really, HRT is just three letters, isn't it, hormone replacement therapy? And there are different types, there are different doses. And lots of people think the risks of HRT are the same regardless.

And there is quite a difference between different types of HRT. So we need to talk about that if that's okay. And then also about what the evidence showed and what we're told. as healthcare professionals actually because the two don't go hand in hand either. So shall we start with HRT and the different types? Would that work with you? Yeah, absolutely. I think probably one way to start is to look at what we know in relation to risks,

both in relation to HRT itself and in relation to lifestyle factors that can be modified. So let's use this sort of scenario. Let's take women in groups of a thousand. And let's take the women aged between 50 and 60. And let's follow them up over a five-year period. So let's start off with a thousand women, aged 50 to 60, perfectly healthy, have a baseline mammogram, which is normal. And if you follow them over a five-year period,

23 of these women will develop breast cancer. Now, the point there is that breast cancer is obviously common. If 23 women out of 1,000, over 5 years, develop breast cancer. It is a common cancer. Indeed, it is the commonest cancer in women in the Western world. So it is important for us to address the issue. Now, if you take another thousand women who are otherwise healthy and at baseline have a normal mammogram, over a five-year period, if you give them HRT, because they are in the 50 to 60-year brackets and the menopausal,

or perimenopauseal, so if you give them HRT, because these women have had nothing done to them, so they have a uterus in place, you need to give them a combination of estrogen and progester as a minimum. The estrogen is addressing the symptoms of the menopause. The progesterone really is specifically being given to protect an overgrowth of the lining of the womb, which may over time become cancerous. But that is the sole reason for giving progesterone. So if you take this 1,000 women and follow them over a five-year period, then the number

of women who develop breast cancer doesn't. increase by four. In other words, a total of 27 women instead of the background, 23, will get breast cancer. I'm deliberately saying this slowly because these numbers are very, very important to understand. So, yes, combined HRT, combined meaning estrogen and progestrogen, will increase the risk of breast cancer by four in a group of 1,000 women. Now, you might think an added 4. And added four women is a huge increase in risk. Other people may think that's a tiny drop in an ocean. It is up to each woman to decide. But while anyone is thinking about it, let's take another thousand women who have had, for whatever reason, a hysterectomy, usually say for heavy periods

or something like that. So they've had a hysterectomy. They are between age 15 and 60, and we follow them up over a five-year period. But we give them HRT. Because they don't have a uterus, we don't need to give them progesterone. The number that gets breast cancer is actually lower than 23. 19 women will get breast cancer for less than background. You could therefore say exposure to estrogen in the form of estrogen only HRT does not increase the risk of breast cancer. If you are actually bold, you might say, is, estrogen actually protecting women.

Now, what we know, based on evidence from the WHO, the Women's Health Initiative Studies in the United States, is that these trends have been shown repeatedly over a 20-year period. In 2020, the WHO published the, I think, Fifth or Sixth report in which they demonstrate that estrogen-only HRT, in other words, estrogen given to women without a womb, resulted in a lower risk of developing breast cancer. But in addition to developing a lower risk, those women who do develop breast cancer on estrogen-only, HRT, actually tend to have a lower mortality from their breast cancer. So the incidence, the rate of developing the disease is lower and the mortality from the disease is lower. So this is the solid evidence base for saying estrogen only does

not increase the risk of breast cancer. Now, it's important also to look at things in perspective. In other words, with respect to modifiable lifestyles. So let us say the obvious, which is to say a woman being overweight, women with very high BMI's, their risk of breast cancer, and of course other diseases is significantly higher than background. In this instance of a thousand women, there is an additional 24 women get breast cancer, cancer if their BMI is 40 and above over the same period of time without taking HRT.

So the point here I'm making is that being significantly overweight is by far a bigger risk, puts a woman at a much bigger risk of getting breast cancer than taking a chart. So in other words, 47 women as opposed to a background of 23 develop breast cancer. Another modifiable lifestyle is alcohol. So if a woman drinks two units of alcohol per day, the risk increases by five. In other words, a total of 28 women, as opposed to the background of 23, will develop breast cancer.

So think about it, alcohol does increase your risk of breast cancer more than combined HRT does. This is true for smoking, which increases the risk by 3, in other words 26, as opposed to 23. And on the other hand, exercise, just two hours per week will significantly reduce your risk by 7 to 16

over the same time period in the same number of 1. women. So the point I'm making here is that again that it's not just HRT, lifestyle factors are terribly important in the risk of this terrible, terrible disease that is breast cancer. And it is important to remember that in my view, the problem with breast cancer, of course, is that women who develop it have had a triple WAMI, really. Whammy one being that they have developed cancer. I mean, that's a terrible thing in itself.

Wami two, being that they have developed a cancer in an organ that is really central to a woman's sense of femininity. And Wami three, being that, and we can discuss this in detail, in a different setting. But the treatment for breast cancer, not only is it, well, disfiguring if you like, but it also often prohibits the use of HRT in the eyes of many people

and often results in a worsening of the symptoms of the menobos. So that the quality of life of women who develop breast cancer is to some extent worsened by the treatment or lack of treatment that they receive. So it is a very important issue to be addressed, and it is a very important issue for both the women themselves, but also for their healthcare professionals. I want to pose there briefly, Lewis, to let you come in on comments before I go. I mean, it's also interesting, and I think just to summarize, really, because when we talk about risk of anything, it's quite hard to quantify, isn't it? Because every time I get in my car and go for a drive,

there's a risk of a car crash. Now, the risk is small. But if I drove at 30 miles rather than 15 miles an hour, my risk probably doubles, but that risk is still really small as well, isn't it? And then the numbers are quite hard. So we're talking about numbers of women who are getting a disease, but we actually, sometimes it's better to say the majority of women won't get it. Do you see what I mean? And it's the way it's pretty, it's pretty, presented can be really difficult for women because I know I had an operation recently and someone said there is a risk of, they always say, don't it? A risk of infection or risk of death. You know, when you sign the consent form, it's really scary. Of course there's a risk, but the risk is small

and I want to know, what is it for me? Am I going to get it or not? I don't mind about the other 99 women actually at the time. It's about me. And no one can give you that answer. So I think I find, as you're explaining so eloquently, it's looking at comparing with other risks. So that risk of so many per 1,000 can be quite difficult to know. But then you compare it with another risk. So like this whole driving thing, it's more risky the faster you drive. We all know that. So it's the same of this with the risk factors for breast cancer.

It's more risky if you're overweight. It's more risky if you're drinking alcohol than taking HRT. But not all types of HRT because you've already said estrogen on its own seems to be very almost protective of breast cancer, which is really like, puts a spiller in the works because everyone keeps saying, well, estrogen causes breast cancer, but you're saying from the data, estrogen doesn't cause breast cancer,

and we'll talk about that again in a minute. And then the progestogen, so the combination, the progestogen that's protected lining of the womb, the studies have really shown this older synthetic progestogen, but even then that number is very small and it doesn't even seem to be statistically significant, which is very interesting. But then we don't really prescribe that,

Many women have the marina coil, which the projection doesn't go into the whole body, or they have the natural body identical progesterone, this micronized progesterone. And the studies haven't shown definitely there's this increased risk. So it's quite an uncertain risk, really, isn't it, if it is there? But it's very low, even if it is there. Yes. I mean, I think that was the next area that I was going to cover, really, that while it is true to say a combined HRT is to change.

and progestergen, does, or is associated with a slightly increased risk of breast cancer, there are approaches to minimizing or reducing that risk. And those ways you have already alluded to, but probably need to be emphasized. I think the use of the myrina coil, the coil that produces the hormone, progesterone, locally, is in theory likely to reduce the risk. The progesterone is being produced precisely where it is required inside the womb, thinning the lining of the womb and reducing the risk of endometrial hyperplasia or endometrial cancer, but not being exposed to the rest of the body in any significant way.

Now, that has to go some way towards reducing the risk that progesterone appears to pose. I must add here that we don't have the amount of research evidence to prove this point, but it's a theoretical assumption which makes teleologic sense. But the other approach, which again you have alluded to, is this idea of using micronized progesterone, eutrogestion, which is taken orally, but is thought to significantly reduce. the risk. So in other words, if we can avoid or minimize taking the HRT orally, we may well reduce all risks associated, including things like blood clots and so forth. So if we were to use the gels or if we were to use the patches or if we were to use the implants, we are likely to

further reduce the risks. The progestogen, as I said, the myrina, the eutrogestin, unfortunately that's taken by mouth, or the patches that contain progesterone as well as the estrogen, all of these approaches would go some way towards producing the risk of breast cancer. Which is very interesting, but then let's just think about breast cancer because there are different types of breast cancer and people generally are told they have an estrogen receptor positive or an estrogen receptor negative breast cancer. So a lot of people then equate an estrogen receptor positive cancer to meaning that it's being caused by estrogen.

So can you explain, if you don't mind, what estrogen receptor positive means and how it equates with estrogen? Well, first of all, let me start by saying you cannot develop a breast if you don't have estrogen receptors. So the very fact of the existence of a breast means that that tissue will have receptors for estrogen, you know, the breast tissue will have receptors for estrogen. So when people say a cancer is estrogen receptor positive, what they mean is that they have tested a piece of the tissue and shown that it contains receptors for estrogen. That in no way implies that estrogen

caused that cancer. Because every woman's breast will contain estrogen receptor. And and the vast majority of women, as you intimated at the beginning, do not actually get breast cancer. But here's the thing, that research has shown that when women who develop breast cancer and their cancer appears to have estrogen receptors, if you give them estrogen, there appears to be an accelerated progression of the disease. Now, I would like us to discuss this again in more detail because I think it's such an important issue. But their studies that show that. And for that reason, many a breast surgeon and an oncologist will say,

if a woman has an estrogen receptor positive cancer, they should not be given estrogen as HRT. Now, let me just say, though, something very, very important here, which is to say that when a cancer of the breast has lost estrogen receptors, what that actually means is that that cancer has become quite aggressive. It has moved away from being like normal tissue, because normal breast tissue contains estrogen receptors. So although people will say, well, if you give them estrogen receptors,

then you don't make the cancer worse. But that actually means that that cancer has become worse because it's lost normal characteristics. Now, the reason I want us to discuss this again is I immediately feel that it may cause confusion in many quarters, in many people. But the fundamental point I will make again, which you asked about, is this. Having estrogen receptors on a cancer of the breast does not mean that the estrogen caused their cancer, because all normal breast tissue will contain estrogen receptors. There is research that says that if you give estrogen to such women that their cancer may become more aggressive.

But these are issues that I want to discuss in more. Absolutely. We'll save that to the next podcast. But I think that's very interesting. And actually, we have estrogen receptors on every cell in our body as women. So, you know, if you took a bit of muscle out of my arm or a bit of cheek from my face out and look down the microscope, you'd find estrogen receptors on this. Absolutely.

And I think that's really important to know because actually I speak to a lot of women and I sure you have over the years who feel really guilty because they've taken HRT and then they've developed breast cancer. And I think for those people listening, if they themselves or someone they know, it should be really reassuring for them to know

that their HRT is very, especially the estrogen in their HRT, really hasn't caused their breast cancer. And some studies that were sort of discredited really that came out in the 90s. There was one called the, it was a nurse's health study, and then there was a million women's study. And these were observational studies. And actually, that doesn't prove cause and effect. And that's why we don't use the data in those studies anymore. And it's a bit like, I always think, maybe I'm too simplistic, but if a woman's have breast cancer

and then you say to her, do you clean your teeth every morning? And she says, yes, I do. Then do you say, oh, right, cleaning your teeth has caused breast cancer? Of course you don't. because common sense will tell you that. But when you try and find something in data, you can always find an association, can't you? And we've all seen slides in medical lectures about women who have electric blankets increase their risk of breast cancer. And of course we know, how would that make any different?

But there are these things, aren't there? And then that makes women feel really quite guilty for what's happened in the past. So I'm hoping just your really wise words there will reassure people, actually, because I think that's really important, isn't it, that people know? Absolutely, absolutely. I think as you intimate, people often look back and think, what did I do that has caused this without realizing actually that maybe it's your genetics, maybe certainly there isn't an active thing that one does, that gives them breast cancer.

Yes, there are situations where they are strong genetic causes, and this is a slightly different ballgame. And whether you give VHIT to these women or not is something that, as I said, we can discuss on another thing. But I think it's important to reassure women that taking estrogen does not itself increase their risk. That, in fact, it could be protective. Yeah, and I think that's very interesting, is it? And I think actually sometimes common sense can be really useful, actually, because if you think even if we didn't have any evidence and we use common sense,

if breast cancer was caused by estrogen, there'd be lots of young women who clearly have very high levels of estrogen in their body compared to older women developing breast cancer. And then women who are postmenopausal who by nature of being postmenopausal if they don't take HRT have low levels of estrogen. So you would look at the numbers and you'd say, well, it would be far more common in younger women. But actually, breast cancer is far more common in older women And because, like you say, some of its genetic, some of its lifestyle, some of its bad luck.

But the older we get generally, the more likely we are to get any type of cancer as well as other diseases, aren't we? So even if we had no data, we could say, well, let's just take a sit back and let's think about common sense. And it's all there really for us, isn't it? But it's just this sort of noise that's gone on. And I think the problem is also, before we finish, I just want to talk about HRT for one more minute, because whenever we Google HRT, even the NHS website, will tell us about risks of HRT. It will say about risks and it will say about clot risk,

which we know we don't have through the skin estrogen, but it also will say about breast cancer. So you've sorted that out for us, which is great. So can we just spend two minutes talking about benefits? Because actually we know from guidelines, the benefits outweigh the risks. And as individual women, I think it's really important that we are aware that HRT doesn't,

equal risks, it equals benefits, and there may be some risks for some women, but most of us don't have risks of taking HRT, actually, because it's our natural hormones. So can you just explain? I know you've done it on previous podcasts, but there's no harm in repetition, just what the benefits of taking HRT are. Yes, I mean, I think the most effective treatment for the symptoms of the menopause, which is why the majority of women take HRT, the most effective intervention is hormone replacement in the form of estrogen and or testosterone. There aren't any other preparations or medicines out there that will deal with hot flashes any better,

that will deal with night sweats any better, that will improve the moods or the skin or the hair, or the nails or the libido or prevent vaginal dryness better than the HRT. been talking about. But there are other not so obvious or not so well-known benefits. And these include a boosting of a woman's immune system. So we know that with the current pandemic that bedevils everybody's life these days, that if a woman is on HRT and she contracts this wretched virus. She is 50% less likely to succumb to the virus than if she were not on HR. Now, not many people know this and this is not widely shared out there, but HRD does boost the immune system.

And this has been shown not just for the coronavirus, but it has been shown for other pandemic-prone viruses as well, that HRT appears to boost the immune system in a positive way. Then, of course, earlier this month, the BMJ came up with a paper showing that estrogen does not increase the risk of dementia. And actually, if you look deep enough, you find that there is increasing evidence from either animal studies or cellular studies or indeed small but increasing human studies, that would suggest that estrogen tends to protect against the development of Alzheimer's in particular. It might say, oh, what is the basis of that?

Well, we know that Alzheimer is a pathology that develops in a part of the brain called the hippocampus. And in that part of the brain, there are loads of receptors for estrogen before the menopause sets in. After the menopause, the receptor density begins to dwindle. And it is possible or highly likely that estrogen, by stimulating those receptors, actually protects against Alzheimer's disease. I obviously can't go into the details of this at this moment in time because it's a little bit protracted to explain it. But the bottom line being that estrogen does not increase the risk of dementia, but may protect against. And then, of course, it protects against brittle bones, osteoporosis,

which is the major scourge in women in the postmenopausal age from the point of view of risk of fractures and increased disability. And so osteoporosis is a big, big issue, and estrogen testosterone are important in protecting against those. HRT also protects against cardiovascular disease. After the menopause, women's risk from cardiovascular disease catches up with men. But HRT is protective against that, especially if HRT is taken through the skin as gels or patches or implants. It is. And actually, when you look at some of the data, we've got some data from women who've had very early menopause and all diseases.

So even things like lung disease, kidney disease, mental health issues, all sorts, isn't it? Because the hormone estrogen is so important to our bodies. And I just want to reiterate just before we finish about this immune protective effect. Because we have known for decades that estrogen switches on the way our immune cells work. So the cells at bite infections, they can increase the number, they can reprogram them, they can make them more efficient. They can calm down all the chemicals that are produced from these cells. which if they get out of control, it can cause this thing called a cytokine storm, so they can attenuate the cytokine storm.

So they're very clever. So I'm sitting here, gloating, but I'm a female. I'm feeling sorry for you, Isaac. Even though you have got a bit of estrogen in your body because men have a little bit. It's a very powerful hormone. And I think the last 20 years, we've forgotten about how important it is. And so I'm really grateful for you spending some time today to just explaining the risks that aren't really risk. Because if you so much, I mean, they're certainly not for estrogen and the benefits as well.

So before we finish, I just really wanted three take-home tips, if you like. So three reasons why estrogen or estradiol is a really important hormone for women and how just link it in somehow with this breast cancer risk would be amazing. Okay. So point number one is that the evidence such as we have and its strong, is powerful evidence is that estrogen does not increase the risk of breast cancer and indeed could be protective against breast cancer. That is an important take-home point. The second take-home point is that when women develop breast cancer while they are in estrogen, and I'm talking about women who are on estrogen only, and perhaps estrogen and the myriadine

then the risk of dying from the breast cancer is reduced compared to women who are not. So the mobility and mortality from breast cancer when women are on estrogen-only HRT is reduced. And the third point to bear in mind is that the benefits of HRT are way beyond the alleviation of symptoms of hot flashes and night sweats. And that they include protection of the cardiovascular system, prevention of osteoporosis of brittle bones, a boosting of the immune system, and potentially prevention of the horrible, horrible dementia of Alzheimer's disease. So those are the take-home messages that I'd like to leave the audience with today.

Amazing, really, really great, very powerful words. And certainly in this podcast, there's a lot to listen to. Some people might have to listen to it more than once, but every word counts. And I'm really grateful for you giving up your time for this, Isaac. So thank you very much yet again. My pleasure. For more information about the perimenopause and menopause, please visit my website, balance hyphen menopause.com. Or you can download the free balance app, which is available to download from the App Store, or from Google Play.