Managing Hormonal Therapy Side Effects

This podcast episode is made possible by AstraZeneca and Daiichi Sankyo. 

Welcome to The Breastcancer.org Podcast, the podcast that brings you the latest information on breast cancer research, treatments, side effects, and survivorship issues through expert interviews, as well as personal stories from people affected by breast cancer. Here’s your host, Breastcancer.org Senior Editor, Jamie DePolo.

Jamie DePolo: Hello, thanks for listening.

I’m joined by Dr. Hope Rugo, a world-renowned breast cancer expert who is division chief of breast medical oncology and a professor of medical oncology and therapeutics research at City of Hope, a cancer research and treatment organization. She also serves as director of the Women’s Cancers Program for City of Hope’s national network of cancer centers. 

At the 2025 American Society of Clinical Oncology annual meeting, Dr. Rugo chaired a session on managing the side effects of new breast cancer treatments and also presented information on how to manage the side effects of hormonal therapy medicines, which are used to treat hormone receptor-positive breast cancer. She is going to share some of that information with us.

Dr. Rugo, welcome to the podcast. I know at the meeting you only had about 12 minutes for your presentation, so I’m hoping we can get a little more in depth in this conversation.

Dr. Hope Rugo: That sounds great. Thanks so much for highlighting this.

Jamie DePolo: So, the older hormonal therapies, I’m thinking specifically tamoxifen and the aromatase inhibitors, are prescribed for five to 10 years after breast cancer surgery, which is an incredibly long time compared to some of the other treatments. And we know that up to 50% of people, primarily women, stop taking tamoxifen or an aromatase inhibitor because of side effects. So, as an oncologist how do you handle that? 

Dr. Hope Rugo: I think that what’s most important in managing the side effects of endocrine therapy in women with early-stage breast cancer is a shared decision-making process. So, I think that understanding what the potential benefits are of the treatment options and the risks of the cancer help a lot to try and work together to find solutions to having the optimal treatment for the individual patient.

So, you may think of an optimal therapeutic approach, you know, from the physician’s standpoint this is the best treatment for you. But we have to balance that with tolerability and having people — we always say some endocrine therapy is better than none — that we really want to balance those side effects with the ability to tolerate the treatment. 

Now, understanding what an individual person’s side effects are, so what are the barriers to treatment, what is the impact of treatment on quality-of-life, I think plays a critical role in helping to, you know, helping to make the treatment work as best as possible for the patient.

So, you know, hot flashes play a really big role in tolerability, trying to work through the treatment options for hot flashes where we saw some exciting new data at ASCO about a non-hormonal treatment that really significantly improved hot flashes and didn’t have the side effects of our currently available drugs. That was great, but you know we have to work through that with each patient because many insurers won’t allow, cover these new expensive shiny drugs, and so we have to work through the first steps. 

You know, we’ve done lots of trials looking at different drugs to help hot flashes, so we have to work through those initial drugs and find out what’s the best treatment for an individual patient. You know, it’s an amazing thing, you know, hot flashes sound like, you know, of course, you go into menopause you get hot flashes, but they can impact so many aspects of life. You know, impact what happens during your daily life if you’re working, giving a talk, sleeping, you know, we all need to sleep. We’ve learned about the importance of sleep and if hot flashes disrupt sleep, it not only makes people tired, but it affects their mood, irritability, their interaction with their family, their ability to work, so all of these things play a really big role.

There are a lot of other aspects of endocrine therapy that are important for women. The other, I think, most important aspects for aromatase inhibitors are that they cause more vaginal dryness and all of our treatments, including early menopause from either the treatment we give in the form of chemotherapy or intentionally shutting down the ovaries to try and reduce estrogen feeding the cancer, can cause sexual dysfunction as well. So, that is a whole nother area that’s poorly discussed and managed. So, talking about the ways to manage those side effects can play a big role. And then for aromatase inhibitors they can cause this funny symptom, joint stiffness and aching, you know where you just feel stiff. People will say I feel like an old lady, you know, not that all older women feel stiff, but that’s sort of the general feeling, and managing those, that side effect as well is really important. 

So, what if you do, you take all the magic tools out of your toolbox and you work really closely with a patient, but the side effects are just intolerable? It’s better to try alternative medications than to just be pushing down the same path. That’s what I think.

It’s interesting, both of these areas sometimes are just missed in clinical practice. You come back every six months, we don’t have tools for, you know, getting the side effects out, trying to understand what people are experiencing, and also managing those in between the visits. 

So, we want to encourage that open communication in between visits, and extra visits as needed, and then trying to think of alternatives is really important. Do you need a short break? Should you change the aromatase inhibitor? Which in some studies have shown improved symptoms and I’ve seen it. Would you be better off taking tamoxifen for a while? Or is tamoxifen intolerable and we should try an aromatase inhibitor? So, these are all really important aspects.

At the same time, we’re studying new hormone drugs, which have less of some of these most bothersome side effects, and those, you know, we won’t have those data for a number of years, but they may provide additional alternatives.

Jamie DePolo: Right. And I guess what I’ve heard from some people is that they just stop and they don’t tell their oncologist. And what you were saying about shared decision-making, I feel like it’s so important that the person talk to their doctor about any side effects they’re having and as you said, explore those options rather than just stop and then go in six months later and say, oh, I couldn’t handle the side effects. I just quit. 

Dr. Hope Rugo: Yes, and I think that you make such an incredibly important point that, you know, I tell patients  that they’re their own best advocate all the time. And you know you want the best for yourself. You don’t want to be dealing with cancer recurrences, but you also want the best quality-of-life and making these decisions and being open with your medical team make the, you know, really helps the most, this is the best plan.

So, you say I just cannot take this medication anymore. People are afraid to go back to their healthcare providers because they’re afraid of, I think, a few different things. One is that, you know, people will be mad at them, they won’t want to take care of them anymore, they will think less of them. But none of that matters, I mean, really none of it matters. 

What you want is the best for you as a person with breast cancer trying for the best outcome possible. So, what you want is to be able to have an open conversation with your healthcare team where you talk about the risks and benefits. It’s a balance at every step of the way. So I really encourage women to be open and discuss this. You know, if I’m seeing a patient for follow-up for early-stage breast cancer, I’m going to ask them pointed questions. And I encourage the healthcare providers to do this because sometimes, again, there’s just so much barriers for sharing this information that you’re going to miss something that’s really important. 

And early in my career, when I had a patient, who unfortunately had recurrent metastatic disease, and I was trying to go back and figure out, because she couldn’t remember when she had stopped taking her endocrine therapy. And when we asked the pharmacy she had actually only filled one prescription. She just didn’t want to tell us. And I really changed my approach and I say, like, do you miss the medication? How often do you miss it? You know, are you able to take it? I’ve also encountered, you know, patients who are angry because they haven’t had someone who’s willing to discuss with them alternatives and is really hearing what they have to say. So, I encourage patients to find the right provider for them, the right provider team. 

I really believe that we function best, as healthcare providers, as a team with our allied health providers, our allied practice providers. So, these could be nurse practitioners or physician’s assistants. We have survivorship programs where the providers are really trying to help with symptom management and also really understand what the barriers are to treatment. So, what you bring up is so important, but it’s important on the provider’s side. I always feel like we’ve really failed a patient when a patient stops taking the medication and doesn’t tell us. 

Jamie DePolo: Right, right. Now, I also wanted to ask you about the SERDs, selective estrogen receptor downgraders or degraders, whichever we want to call them. Faslodex, Orserdu, and then at ASCO we heard more about camizestrant and vepdegestrant. How are those side effects different? I know people may not be on them as long or maybe not, I mean, I guess they might if they’re taking them for metastatic disease. Are those side effects different than tamoxifen and the aromatase inhibitors? 

Dr. Hope Rugo: They are and I think that we won’t have as good a feeling about the side effects until we see more quality-of-life data from the early-stage setting, because patients tend to tolerate medications like endocrine therapies better for metastatic disease than early-stage disease for reasons that aren’t entirely clear. But these medications, the symptoms are different.

The oral SERDs, you know fulvestrant, which is an injectable SERD, is only approved for treating metastatic or advanced breast cancer. You get the injection, you can have hot flashes, some joint stiffness, but overall I would say that outside of the injections for most patients, the symptoms are less, the ones that I talked about, and we see more symptoms from causing menopause in young women, for example, where if they haven’t been in menopause before, in that situation we’re using aromatase inhibitors.

So, by the time you get to Faslodex, or fulvestrant, you’ve already been on, you know, already had ovarian suppression or been in menopause for a while, so we aren’t seeing as many of those symptoms.

The oral SERDs have their own unique symptoms, so when you take a pill you might have a little nausea, you could have diarrhea. One of the drugs, and probably more of them, the drug where we’ve seen this is camizestrant, can cause some flashing lights, which don’t seem to bother patients very much and get better over time, when you go from a light to a dark room and they’re fairly brief. But these kinds of side effects have been observed in our trials treating patients with advanced cancer.

I have participated in one of the trials where you switch from an aromatase inhibitor to an oral SERD in the early-stage setting with patients who have quite high-risk disease. And what I was interested in, they’re not, it’s not blinded so you know what patients have switched to, is the reduction in symptoms. So, initially with that switch, several of my patients have just had less of the joint stiffness that they were already managing very well. Not a big change in the hot flashes, and over time other symptoms, you know, maybe a little bit of nausea, but the symptoms are quite different. We don’t have any of those drugs available to treat early-stage breast cancer yet. 

If a patient has multiple local recurrences and we’re searching for an endocrine therapy we do have fulvestrant, but there are now four oral SERDs that have been tested in randomized trials for patients with advanced cancer and been shown in certain subsets to be better than our standard injectable SERD fulvestrant. And you don’t have to go into the center every month to get two injections in your butt, which is, I think, for many people an advantage.

It just won’t be for all because some people have trouble with oral medications. So, we’re going to see a lot more data because at least three of these agents are being tested in high-risk early-stage breast cancer, elacestrant or Orserdu, imlunestrant, which has positive results, and camizestrant. 

Jamie DePolo: Okay. And you kind of talked about hot flashes, joint pain, being the top hormonal therapy side effects. Are there any others that seem to rise to the top, that seem the most common among the most people? 

Dr. Hope Rugo: There are a number of other side effects, of course. You know there are just symptoms associated with menopause. And you know women for a long time have also noted that they have some changes in executive function, so to speak. It’s such a funny term, but you know memory loss, et cetera. But also hair thinning can be an issue, and for those of us who have had the fortune to get older, hair thinning is an issue. And for some of the treatments, for example, we’re adding targeted agents, called cyclin-dependent kinase 4/6 inhibitors, we call them CDK4/6 inhibitors, to patients who have early-stage, higher-risk, hormone receptor-positive breast cancer, they enhance the hair loss. 

So, we’ve been using an old drug, repurposing old drugs it’s now called, this drug was used for high blood pressure when I was training, you know, decades ago, caused a lot of side effects, but one of the side effects was hirsutism and that means extra hair growth. So, using very low doses of this drug called minoxidil has worked wonders for many of my patients who had thinning of their hair, which has just been awful for them, you know, even requiring wearing a wig for some older women who already had thinning hair, and it has very little side effects. The main side effect is growing hair other places and that’s very individual, interestingly, and of course you can get rid of that hair. So, that has, I think, been an important area as well. 

There are side effects we can’t see, obviously. And one is thinning of the bones. And it’s really important to monitor bone thinning over time with bone density tests and we have now medications that actually will prevent further bone loss, which is exciting, and build up bone, but we have to watch out for the side effects from these medications. You can reduce fractures, but you want to make sure that you’re not creating too stiff a bone by treating for too long a period of time.

You also need to make sure that people don’t have problems with their dental work because they, if you have sort of, you know, festering infections or problems this can create an odd problem called osteonecrosis of the jaw. But I have found that now we’ve mandated having a dental clearance before anybody, you know, they go see a dentist, they say I’m going to take a bone-targeted drug, is this okay? And once we started doing that I have not seen, knock on wood, a single case of osteonecrosis. 

So, I’m very pleased about that just very simple approach to trying to preempt a side effect. And there is a little bit of data, again it’s not part of the approval for these drugs, but for one of them that’s given intravenously every six months there is some data that it may prevent growth of the tumor or spread of the cancer to the bones and it might improve survival. So, around the world there’s been more enthusiasm of giving these drugs if there is some thinning of the bones, mild thinning of the bones, in higher risk cancers, in particular, because of this effect on outcome.

Jamie DePolo: Okay. And you mentioned executive function. I think a lot of people would think of that as chemo brain, but it reminds me that there was a study I saw, and this was a while ago so I apologize I don’t remember when, but it linked hormonal therapy to chemo brain, essentially, saying that, you know, the sort of forgetfulness or having trouble making decisions could be tied to hormonal therapy as well. Am I understanding that correctly that that’s what you are talking about, correct?

Dr. Hope Rugo: Yes and thanks for clarifying that. We used to call it chemo brain. And I actually did two studies looking at you know chemo brain and trying to document it. We had enormous problems because the standard cognitive tests, which really are evaluating patients who have significant cognitive problems, they take two hours, they’re really expensive. There’s a learning issue, so as you get better at it, you know, you can have better testing. You know even the shorter tests just didn’t get to what drives us crazy. You know when we are noting the normal effects of aging, you know, word-finding problems, forgetting why you walked into a room. Again, it’s this funny short-term memory loss that can really drive people crazy.

And so as we’ve given better supportive care for chemotherapy, but I think most importantly given less intensive chemo. Like, we give, you know, we’re more likely to give weekly chemo than to give it as bigger doses infrequently, in many cases, we give four cycles instead of six cycles. You know, we haven’t amplified the dose of chemo drugs that didn’t help. I have really seen a tremendous decrease in that symptom for the majority of patients. So, where we’re seeing it is more with endocrine therapy. And it’s interesting there have also been some studies trying to look at whether there’s a risk factor or a unique patient population who have more of these symptoms. 

We’ve never been able to really figure it out at all. And again its complex because it’s affected by so many other things, and of course something we call polypharmacy or many different drugs. If you’re having a lot of hot flashes and you can’t sleep and you’re taking something for sleep, or you might be taking something for hot flashes, that may also affect a little bit of maybe, you know, the quickness of remembering a word, responding, thinking of the next topic, remembering why you walked into a room, and where your cell phone is, you know. Siri has helped us a lot with that particular problem, where are you? Which I do all the time. But I think that, you know, and it’s interesting we have tools now that can help, which is great. 

We’ve also learned that there are things we can all do to help ourselves when we age, even outside of taking hormone therapy, which is you know doing, I think, things that exercise our brain. You know, people have talked about Sudoku and crossword puzzles, none of which I do. But keeping your brain active in whatever way works for you, just like keeping your body active, plays a really big role. Exercise, for example, not only does it help with some of this cognitive, milder cognitive complaints, but it also helps with joint pains and stiffness, which is helpful, and it helps with mood. So, there are some things that we can do for ourselves that make a big difference here. 

You know, I think that sleep plays a huge role in our cognition and the impact on cognition mood, for example. I have found something, which is not well described, but you know sometimes when women, in particular, because we see women the most with breast cancer. I’m not meaning to leave men out, but we certainly see women the most. They finish the chemotherapy, you know, we’ve caused menopause for younger women, and they’re trying to go back to their lives, there can be a sense of standing on the edge of a cliff waiting to see if you’re going to fall off. So, you know, you have been doing something that’s very focused, time-consuming, and has side effects doing chemotherapy for, to prevent the breast cancer from coming back. Then that all stops. 

You finish your radiation if you needed it, you know they ring the bell, you’re done, you walk out, and what are you left with? You’re left with the fear of recurrence, and you’re left with the side effects of your treatment, and feeling as though to the outside world you look the same, but inside you feel very different. And what I found is that some people really experience a significant depression during that time and we call it a reactive depression. So, this, you know, it’s important for the providers and the patients to have an open discussion about that as well. I have found that short-term use of very low doses of antidepressants can help with this. Of course, there are other support mechanisms, including groups that meet to talk about how things are going, support groups, groups focused on young women with breast cancer, et cetera.

That can really help work through some of these issues, but the low doses of antidepressants also help with hot flashes, which can help women sleep. So, we use another drug that was really developed for children with seizures, but it caused a lot of sleepiness at the doses required to prevent seizures. So, we give little tiny doses at bedtime, even though the label says to take it three times a day, this drug is gabapentin, we give little doses at bedtime and escalate as needed, and that can help with sleep and hot flashes. But you know one has to keep in mind that these drugs are given for a specific symptom, and if somebody is feeling excessively sleepy or having word-finding problems, you need to also be thinking about whether you can switch some of these medications for something else or even taper them off to try and improve those symptoms. So, this is an ongoing process over time.

Jamie DePolo: You must’ve been reading my mind when you were talking about exercise. Because I have read some small studies that showed that exercise can help with a lot of the hormonal/endocrine therapy side effects. And I just wondered how difficult is that to integrate into cancer care? I know there was some big splashy exercise research presented at ASCO as well, specifically in colon cancer, but possibly could apply to breast cancer and prostate cancer from my discussion with the PI. So, I’m wondering is it, is it difficult? You know, you’re talking about prescribing medicines for specific side effects, but exercise seems so much more general. Is that harder to integrate into the care?

Dr. Hope Rugo: Boy, that study was so exciting, for me, to see something that, you know, was published the same day it was presented, that you could change outcome, you know, to some degree along with our standard treatments by exercise. What an exciting next step and there is an ongoing trial looking at this impact called the BWEL trial that is run by Jennifer Ligibel and is sponsored by the National Cancer Institute. That trial has completed enrollment, but it’s following patients over time. And the trial specifically included women who had increased weight, so were overweight by our standard criteria. But I think that for everyone, this really can impact your well-being and side effects. 

We don’t know about outcome, but overall, weight gain, big weight gain can impact outcomes, so if you can prevent weight gain by doing exercise and managing diet, that’s a win-win, you know, overall.

How do you incorporate it? Your question is really interesting. That, you know, we, you can get your pill, you know, covered by your health insurance, but they’re not covering exercise right now, although maybe someday in the future they will need to cover specific programs. Because if, you know, if we have expanding data showing improved outcome, I mean, that’s such an important aspect of life. 

So, how do you incorporate it? During treatment, I think you have to incorporate what’s feasible for you. I always tell patients, you know, if you haven’t been running, don’t start running during chemotherapy. You know, you want to do exercise that feels comfortable for you and is practical. And then I think after the acute treatment ends, for example the chemo and radiation, you’re on hormone therapy or you are done with treatment because you don’t have hormone receptor-positive disease, incorporating exercise in the way that works for you. If you’ve been an exercise enthusiast, it’s easy. If you aren’t I think you really need the support of your healthcare providers to, you know, suggest places to go and ways to incorporate this.

You know walking upstairs if you’re able to, walking faster. I’m a big walker, you know, I walk fast in the airport, for example. Where you have the opportunity to do more activity, if you don’t have time to go to a gym, it plays a really big role because we’ve found that you don’t have to be doing a stepper or running on a treadmill or running outside. There are a lot of ways to get exercise you just want to get in exercise every day, if you possibly can.

Jamie DePolo: All right. And then finally, if someone’s on hormonal therapy for breast cancer and they’re having side effects that are affecting their quality-of-life, this is sort of a reiteration and you’ve probably said all these things already, but what are the top three or four things you would advise this person to do, like, just step-wise?

Dr. Hope Rugo: I think the top thing is, for women who are experiencing side effects, is first to really think about what’s bothering them the most. Make a list. You know, a lot of times when you go in to see your providers, you’re not remembering all those details. I don’t remember all those details. I make a list. If I’m going to have a telemedicine visit with my primary doctor, I’m going to write a list of the key issues for me, and it has to be the key issues because every visit is going to have some time limitation. So, you really want to be clear. Think about it in advance, write down the important issues so you don’t forget to say them, and make sure you start the visit with I’m happy to be here today, there are three really important issues that I want to discuss. 

And go through them and be clear about whether that issue is impacting your ability to take the medication, or whether or not, you know you’re going to take the medication, but it’s making you miserable. You know, you really have to try and be as clear as possible. And you can do this now where you have access to electronic health records through that system, which of course helps you compose something very clear. You want to be really clear about what the issues are. You want to say what you need help with, what’s going to impact your ability to take treatment, and that you want suggestions for alternatives, and this makes the biggest difference, I think, in managing your healthcare. 

And then you want to go back and say, you know, this didn’t really work very well for me, I couldn’t tolerate this medication. What other options do I have because this means that I can’t take the medication?

Jamie DePolo: All right, Dr. Rugo, thank you so much. This has been so helpful, I appreciate your time. 

Dr. Hope Rugo: Great, thank you so much for having me.

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