How to Ease Aromatase Inhibitor-Related Pain
Ashish Khanna, M.D.
October 4, 2019

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Ashish Khanna, M.D., is a physical medicine and rehabilitation specialist at the Kessler Institute for Rehabilitation and part of the ReVital Cancer Rehabilitation Program. Dr. Khanna completed his residency in physical medicine and rehabilitation at the Kingsbrook Jewish Rehabilitation Institute in Brooklyn, NY, where he became interested in cancer rehabilitation early on. He completed his fellowship subspecialization in cancer rehabilitation at Medstar Georgetown University and the National Rehabilitation Hospital in Washington, DC. He specializes in the treatment of people who have pain or functional issues as a result of cancer or cancer treatments, including people who have been diagnosed with breast cancer. This includes pain, shoulder issues, fatigue, joint pain from aromatase inhibitors, and other issues. He has lectured at numerous international conferences, has published peer-reviewed research on a variety of related topics, and is the co-author of an upcoming book on cancer rehabilitation.

Listen to the podcast to hear Dr. Khanna discuss:

  • what aromatase inhibitors are and how they treat hormone-receptor-positive breast cancer
  • why and how aromatase inhibitors cause joint pain
  • how exercise can reduce aromatase inhibitor-related joint pain
  • other ways to ease this joint pain

Running time: 22:56

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Jamie DePolo: Hello, and thanks for listening! Ashish Khanna, M.D., is a physical medicine and rehabilitation specialist at the Kessler Institute for Rehabilitation and part of the Revital Cancer Rehabilitation Program. He completed his residency in physical medicine and rehabilitation at the Kingsburg Jewish Rehabilitation Institute in Brooklyn, NY, where he became interested in cancer rehabilitation early on. He completed his fellowship sub-specialization in cancer rehabilitation at Medstar Georgetown University and the National Rehabilitation Hospital in Washington, DC.

Dr. Khanna specializes in the treatment of people who have pain or functional issues as a result of cancer or cancer treatments, including people who have been diagnosed with breast cancer. This includes pain, shoulder issues, fatigue, joint pain from aromatase inhibitors, and other issues. He has lectured at numerous international conferences, has published peer-reviewed research on a variety of related topics, and is the co-author of an upcoming book on cancer rehabilitation.

Today, he joins us on the podcast to talk about a topic that is extremely important to him, and I know is important to many of our visitors, which is pain caused by aromatase inhibitors and how that pain can be managed. Dr. Khanna, welcome to the podcast!

Dr. Khanna: Thank you, thank you. I’m happy to be back.

Jamie DePolo: So just in case anybody listening isn’t familiar with aromatase inhibitors, can you explain what those medicines are and how they’re used to treat breast cancer?

Dr. Khanna: Yeah, sure. So aromatase inhibitors are used in hormone-receptor-positive breast cancers. Those are basically the ones that are estrogen- or progesterone-positive, and you’ll usually hear this as ER- or PR-positive. And basically what that means is that if, imagine a breast cancer cell, on its surface it has a lot of different receptors for a lot of different things. One of the receptors it has is for estrogen and/or progesterone. So basically, anytime some estrogen binds to that cell it causes that tumor to grow, so the tumors are essentially fed by estrogen or progesterone.

What we’re essentially doing here is, in order to treat that breast cancer, we need to lower the levels of estrogen in the body, right? So how do we do that? Well, as it turns out, estrogen is being made in the peripheral tissues, like all the different fat cells, a little bit in the liver, things like that. And through taking some different hormones and an enzyme called aromatase that lives in that area, it converts estrogen precursors into estrogen. So essentially what this medication is going to do it it’s going to turn off that enzyme and stop that conversion, so in the end that cuts down the level of estrogen that’s circulating in your body.

And this causes a lot of different problems. One of them is the joint pain that we’re going to talk about today, which, as you mentioned, is definitely an important topic that people aren’t really aware of. But basically what that does is it causes kind of like a chemically induced menopause in a way, right? When we go into menopause our estrogen levels drop, and this a medicine, like menopause in a pill, I guess. So you do get a lot of the menopause symptoms that you get for the same reasons, but, particularly, you get joint pain with these.

There are three inhibitors, the three most common ones that you’ll see are anastrozole, also called Arimidex; there’s exemestane, which is Aromasin; and there’s letrozole, which is also called Femara. The idea is that after you have breast cancer, if you take these medications, it’s chemopreventive, so it’s basically going to prevent your breast cancer from coming back. So when we treat breast cancer, we want to make sure that all of the cancer is gone. We don’t want to leave any cells, or a minimum amount of cells, if possible. So after your breast cancer is treated, then afterwards you usually take these medicines to prevent your breast cancer from coming back. And the thinking was to do it for 5 years. Now, we’re doing it for 10 years for some people, might be better. So you take it for 10 years after being treated for breast cancer for those people who have ER/PR-positive breast cancers.

Jamie DePolo: Okay, I’m glad you mentioned the length of time that someone might take it because I’ve seen studies suggesting that about 50% of women — I believe all these studies were in women, not men — prescribed aromatase inhibitors after breast cancer surgery either don’t take them or don’t take them regularly because of the side effects you’re talking about. And as far as I know, joint pain and joint stiffness is the most common with an aromatase inhibitor. So what is it that the aromatase inhibitors cause this joint pain? Because I know there’s another medicine, tamoxifen, which is given to premenopausal women…

Dr. Khanna: Right.

Jamie DePolo: …and it doesn’t seem to cause this same joint stiffness. So what is it about an aromatase inhibitor that works in the joints this way?

Dr. Khanna: Tamoxifen is similar to an aromatase inhibitor, I guess you could say, in broad strokes. One of the big differences is that we usually give aromatase inhibitors to postmenopausal females, and premenopausal females are the ones who get tamoxifen. So if you haven’t gone through menopause, you’re more likely to get tamoxifen. Tamoxifen works a little bit differently.

So if you think about menopause, the main source of your estrogen is going to be your ovaries, right? When you’re premenopausal your estrogen is coming mostly from your ovaries. When you’re postmenopausal, most of your estrogen is coming from the tissues outside, in your fat cells and things like that, where the aromatase inhibitor works. If you’re premenopausal, we need to address the source of estrogen differently, and that’s what tamoxifen does. Premenopausally, the source of estrogen is from a different place, so that’s one difference. If you’re postmenopausal, that doesn’t mean you can’t be treated with tamoxifen. You can still use tamoxifen in postmenopausal breast cancer, but you don’t see that as often.

Both of them cause joint pain, like you said, [but] tamoxifen less so to some degree, but the aromatase inhibitors as a class also do that. Studies show, like you said, that 50% of women roughly, like you said, are going to report new or worsening joint symptoms. That can go as high as 75% of people, and about 37% of people who take tamoxifen report it. You see it in both, but definitely more so in the aromatase inhibitors.

And then the reason why we think that happens is essentially estrogen deprivation. As it turns out, women have estrogen receptors in the cartilage and the synovial lining of their joints. So you have estrogen receptors in your joints, and if you turn off the estrogen, if you turn off the faucet on the estrogen, then you do get more arthritis-type symptoms. It’s not exactly the same as osteoarthritis because the cause is different, right? Osteoarthritis happens in a lot of the weight-bearing bones and things like that, where you get kind of a bone-on-bone is how people think about it, but this is different. It feels like arthritis, but anatomically [it’s a] little bit different from that, and it just causes some swelling there, and just like arthritis, it can cause some fluid in the joints.

The difference between osteoarthritis and the arthritis caused by aromatase inhibitors [is that with] the aromatase inhibitors, [it] can happen in small joints. You’ve got them in the wrists. You’ve got them in the hands. The wrist and hand is actually the most common place where people get it. About 60% of people who have these issues will report it in their wrists and hands, and about the same amount [in] the knee. Some people will feel it in their spine. The next most common is the ankle or the foot, and the last is actually the hip. So arthritis of the hip is actually very common, right? The hip bone holds a lot of your body’s weight. But the wrist and hand in this case is probably the most implicated in addition to the knee.

Jamie DePolo: Interesting.

Dr. Khanna: Yeah, right, and I see that in the clinic for sure. These kinds of statistics and epidemiological stuff definitely jives with what I see at the clinic. The other thing I wanted to mention really quick is if you already have arthritis, the aromatase inhibitor is most likely going to make that worse, unfortunately. So if you already have anything, like hip arthritis, or you already have arthritis in your spine that’s causing you problems, or in the knee or anywhere, this probably is going to make it worse. It’s not only arthritis. If you have something like carpal tunnel syndrome, even something like that, you can see where it makes carpal tunnel syndrome worse and things like that, too. So that’s the unfortunate part of it.

Jamie DePolo: I guess I’m just curious, and the research may not have been done, but do we have any idea why the hands and the wrists seem to be the most common place for this type of pain?

Dr. Khanna: You know, I don’t know the answer to that. That’s a good question. I’m not aware of that, yeah. I’m not sure exactly why.

Jamie DePolo: That’s fine. And you mentioned that if you have arthritis already, an aromatase inhibitor can make it worse, so it would seem that those particular women would likely be at higher risk for joint pain from an aromatase inhibitor. But are there any other factors that might put someone at higher risk? I’m just going by the comments we get on our Discussion Boards. For some women, it’s excruciating, and they do have to stop taking the medicine or switch to a different one.

Dr. Khanna: Right.

Jamie DePolo: And other women say, “Oh you know, it wasn’t that bad.” So I’m wondering if there are any other risk factors besides pre-existing arthritis.

Dr. Khanna: It may have a genetic component. Some women have more estrogen receptors in their joints than other women do. There’s certainly that. Not everyone is built the same, and everybody is going to respond to the medications differently. It’s the same like menopause, you know? No two women are going to go through menopause the same, and this is kind of like a chemically induced menopause, like I said. So the effects are going to vary, and having a wide variety of symptoms, especially if it’s anything that involves the endocrine system. You know, everybody responds to their hormones differently and different levels of this cause different things, so I think that’s probably the primary reason, because we’re just talking similar to menopause.

Like I said, if you have arthritis going in, it’s likely to get worse. Sometimes people have chemo, they still have the arthralgia, so they still have the joint pain from chemotherapy. So if you still have the joint pain from the chemotherapy that you just went through, that’s going to make that worse. If you have any other underlying kind of pain syndromes, like fibromyalgia — fibromyalgia is kind of like a centralized pain syndrome — that can make your fibromyalgia worse. And then the last thing would be if you had any rheumatological, like rheumatoid arthritis or any other rheumatological problems, that can make that worse as well. So if you have any of those underlying things or a number of others, that’s sort of off the top of my head, but if you have those kinds of pre-existing issues, an aromatase inhibitor will most likely make that worse.

And while we’re talking about things that vary, the different aromatase inhibitors may affect you differently, too. So it’s a great conversation to have between you and your oncologist about perhaps switching to a different one. And most oncologists are going to, if your symptoms are that bad, they’re going to already consider switching to something else. You can’t always be switched to something else, of course. That’s why you have to discuss it with the oncologist. It’s up to the oncologist. They’re the ones who know all of the information about your particular type of cancer and the studies that show which one is best for you to prevent your cancer from coming back. But there’s some evidence, particularly with exemestane, one of the ones I mentioned, with exemestane, some studies are showing that that has less joint pain symptoms. Like I said, not everybody can take that one, but it’s something to mention and bring up to the oncologist.

Jamie DePolo: Certainly, certainly. And now — this is sort of the key question for this whole podcast — how is this being treated? I know there are medicines that people can take, but I’ve also seen some studies showing that exercise can help, acupuncture can help. What do you recommend?

Dr. Khanna: The best evidence we have for the aromatase inhibitors is going to be exercise, like you said. Now, asking somebody who has joint pain to exercise is going to be very difficult, of course, and that’s why there are professionals to help you through those kinds of things. Particularly, if you can find a cancer rehabilitation medicine physician like myself, like a physiatrist, we can certainly help you with that. That’s our area of expertise. Unfortunately, there aren’t that many of us in the country, but there are a lot of wonderful occupational and physical therapists who can help you with this type of thing, and they can make a personalized exercise program for you.

They have these strategies called joint protection strategies. If you have a painful joint, they can basically work around that. So they can help you do some therapy for it. Otherwise, there are some studies showing that just plain old aerobic exercise, just getting moving, can make a difference. So if you can do 150 minutes a week of aerobic exercise, like moderate-intensity exercise — and I usually say moderate-intensity exercise would be when you’re exercising to the level that you can still hold a conversation, right? You’re not completely out of breath, but if you can maintain that for 30 minutes a day, ideally 5 days a week, or even 3 days a week, then that would be great.

Jamie DePolo: So something like brisk walking, like if you were walking pretty fast with a friend, and you can talk…

Dr. Khanna: Yes, exactly.

Jamie DePolo: Okay.

Dr. Khanna: Yeah, especially doing it with a friend and things like that, great. Those have been shown in multiple studies, even large randomized studies, can decrease the reported pain that people have even 12 months later, so even 1 year later.

I think what I forgot to mention, I guess, would be the timeframe of when you start. Usually, you start to feel these joint symptoms about 6 weeks after you start the aromatase inhibitor, and they can worsen over the course of the first year. But generally, after the first year — you know, these are kind of vague numbers — but over the course of the first year, typically symptoms start to stabilize and may improve a little bit. So what they say is, it’s going to get worse at about 6 weeks, and then you know, the worst period of it will probably be in the first year, but if you can stick through it, it may get better after the 1-year mark.

So the exercise is what we have as the best evidence. The other things that you can do are sort of the standard arthritis treatments. If you can take an NSAID, ibuprofen, a non-NSAID would be Tylenol, which works well. And there is some evidence of acupuncture working well, too. I do have a couple of patients who do acupuncture and say it works well, and I have some that do it and said it didn’t really make a difference. It just kind of depends. That one’s a complementary, an alternative medicine. The science isn’t as robust for those kinds of treatments, but if it works it’s worth a shot.

Jamie DePolo: Mm hmm.

Dr. Khanna: For some people, it does work. There are some medications you can discuss with your doctor, too. Probably the strongest evidence we have medication-wise is for something like duloxetine, or Cymbalta. That’s been shown in a really high-level study in the Journal of Clinical Oncology to improve the worst joint pain. So the joint that bothers you the most, it can decrease that. It can decrease stiffness, and then it also can decrease the pain that interferes with your life and keeps you from functioning. So that’s pretty good.

Jamie DePolo: And Cymbalta — I want to ask — that’s an antidepressant?

Dr. Khanna: Yeah, yeah. A lot of the medications we use for pain were originally designed for something else. Actually, Cymbalta is still used to treat depression also as well, so maybe one of the side effects for you might be a mood elevation, right? I do tell patients that, that mood may improve as a side effect. You know, for nerve pain, a lot of people take gabapentin. That was originally a medication for seizures, but it actually works for nerve pain much better. We have much better medications for seizures now. So a lot of these kinds of things were designed for one thing but work really well for something else.

Jamie DePolo: Are there any other sort of complementary techniques or other medicines that might be helpful for someone having this joint pain?

Dr. Khanna: Yeah. Especially if you have pre-existing joint pain, whatever worked for you I would say will probably work for this as well. Using heat. Bracing. Like I said, especially if you see a physical or occupational therapist, it’s a great idea for this issue. I send a lot of patients to physical or occupational therapy. I get the cases of the people, like you said on the forums and a lot of people listening, where they’ve had enough. You can’t function. You can’t do anything, it’s really… you’re so stiff in the morning. You know, people have busy lives and a lot of things to do, so it does interfere with their life quite a bit. It’s too bad.

If you’re taking tamoxifen, you can’t take Cymbalta. Your doctor probably knows that, but you definitely should advocate for yourself. So those of you who are on tamoxifen, you cannot take duloxetine — unless you get your doctor’s permission — and there’s a reason for that. With tamoxifen, if you’re taking Cymbalta, the tamoxifen doesn’t work as well.

Jamie DePolo: Okay.

Dr. Khanna: Yeah.

Jamie DePolo: Definitely good to know.

Dr. Khanna: Yeah, I’m glad I remembered to throw that in there. [laughs]

Jamie DePolo: I’m curious about the exercise, too. Is it possible, say if someone is a regular exerciser and has been. And then she is diagnosed with breast cancer, goes through treatment. It’s hormone-receptor-positive disease. Is being a regular exerciser… is there any protection in that? Could that make somebody less likely to have joint pain from an aromatase inhibitor, or has that research not been done?

Dr. Khanna: Yeah, that has been shown to be the case. That’s actually the case in all the different forms of arthritis — osteoarthritis, rheumatoid arthritis, and then this sort of arthritis that’s caused by the aromatase inhibitors. Using the joints keeps them moving. It keeps them well-lubricated. It just kind of keeps the joints happy in that way. So people who are able to move and able to do more and exercise more — which, I understand it’s not always the easiest thing to do — whatever you’re able to do is beneficial. There’s a response to even a little bit of exercise.

And you know, if you have arthritis and you have it in the weight-bearing joints, and the aromatase inhibitors made your back pain worse or your hip pain worse, your knee pain worse, or ankles, the pool is a great way to do some exercise for people who have access to a pool. That’s a great way because you’re much lighter on your feet in the swimming pool, and you’re able to do a lot more of the exercise that way and have less pain. And there are some physical therapy and occupational therapy places that have a pool, so that’s one option.

Jamie DePolo: I was just going to say, you talked about finding an occupational therapist or a physical therapist who is familiar with joint pain caused by aromatase inhibitors and kind of developing a plan. Is going to your cancer care facility and asking either the oncologist or the oncology nurse navigator, or someone like that, the social workers. Is that the best place to find somebody like that?

Dr. Khanna: Yeah, definitely. The therapists tied to a cancer center or tied to a hospital may be more familiar with this condition than other people would be, for sure. The hospital I work with, which is Kessler, is involved with Direct Medical, and they have a service called Revital Cancer Rehabilitation, which is RevitalCancerRehab.com. You can see if maybe there’s — and those therapists are certainly trained in this, in a number of different issues involving breast cancer, head and neck cancer, those sort of things. So if you live near one of those therapists, you can reach out to them. But any sort of cancer center, the therapists would most likely be seeing other patients for the same issue.

Jamie DePolo: Okay, good to know. Now finally, I’ve just been wondering if there’s a step-by-step process. If a woman came to you on an aromatase inhibitor and was having joint pain, what do you do first, second, and third? How do you approach this?

Dr. Khanna: What we want to do is make sure that your joint pain can be treated in some other way. So if you have hip pain or you have knee pain or wrist pain or something like that, then those can be treated with those different types of medications and also injections, too. So you can do steroid injections. You know, they have the gel shots for the knee if the knee is bothering you and things like that. So that’s one of the major things.

The other thing that I try to do is to make sure that you don’t have another underlying problem, like you don’t have rheumatoid arthritis and things like that. Sometimes I’ll send people for blood tests just to make sure that you don’t have rheumatoid arthritis. There are studies showing that people who have an aromatase inhibitor… sometimes people had an underlying rheumatological problem the whole time.

And then like I said, a lot of these things develop over time. Ten years is a long time, and everybody gets older over 10 years, so you can develop other problems, too, so it’s good to have close follow-up with your doctor for those types of things.

Jamie DePolo: Dr. Khanna, thank you so much! I really appreciate your time and your insights.

Dr. Khanna: Sure, my pleasure. Thanks for bringing some attention to this important topic. I appreciate it.

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