Living with and treating bone metastasis

Transcript

Pallav Mehta, MD [00:00]

We will talk about bone metastases, living with bone metastases. We’ll talk about what they mean, what is a bone metastasis, they’re not all the same, what sort of treatments we have for them.

I have a lot of hats. As Caroline mentioned, I’m with Reimagine Care. It’s a startup company looking at how to extend the care of cancer centers outside the walls of a clinic. I’m a breast cancer oncologist. I also head up the integrative oncology department at MD Anderson at Cooper focusing on things like lifestyle. I have a little more understanding of supplements and nutrition and those sorts of things.

Metastatic breast cancer. If you look here, you’ll see that about 70% of all patients with metastatic breast cancer have bone metastases. So they’re quite common. But then when you look at bone-only metastases and then those with ER-positive metastases. Most patients with bone metastases, about 70%, have estrogen-positive disease. Now, that could be HER2 negative or HER2 positive, but about 70%. But what’s interesting is, when you look at bone only, almost all of them — you can see the diagram there slightly crossing over — about 90% or more when you look at bone only, tend to be estrogen positive. That’s important when we think about how we look at monitoring them and treating them.

Just a word about metastases. The term was first recognized in literature hundreds of years ago and refers to a “change of place, order, or nature; migration or transition.” And this is I think important. When there’s a breast tumor, not every cell in that tumor can actually metastasize. We think, and this varies by different types of cancers and different subtypes, but about 0.01% of a one centimeter tumor has the potential to become a circulating tumor cell. I’m sure everyone’s by now heard these terms, CTC and even ctDNA.

A one centimeter tumor is a billion cells. So 0.01% of those can spread and we are finding in the circulation. But of those 0.01% can actually set up shop someplace else. And so it’s a very small portion of these cells. We’re still learning about what is it about those cells that makes them likely to go places, why do they go certain places more than others. When it comes to bone metastases, obviously the advances in our X-ray and imaging technology with William Roentgen’s X-ray in the early 20th century is how we first started to recognize some of these lesions.

This is a little bit of a soap box here. I’m going to talk just briefly about this.

I’ve been doing breast cancer almost 20 years, and I know in my training and even the training today of fellows, we talk about metastases with these hard boundaries. We say once someone is metastatic, they’re no longer curable. And I think at this point we’re starting to get to an understanding that maybe this is not as hard of a boundary as we once thought.

George Sledge, who I love hearing speak, he was the president of ASCO about 15 years ago, and he was the head of oncology at Stanford for many years. He has this really great article, and if you haven’t read it, you should. It was an opinion piece called “Curing Metastatic Breast Cancer.” In it he says, “We should avoid false promises ... but we should also avoid nihilism.” This therapeutic nihilism that I think permeates our oncology care sometimes. “The journey is worth taking, even if the goal seems elusive.”

What he was saying, if I can summarize this, is that when we think of the word adjuvant — adjuvant and metastatic are essentially the same thing. It’s just numbers. When we give therapy after curative breast cancer, what are we really trying to do? We’re trying to get rid of cells that are floating around in the body. But when we give it for metastatic, that means those cells have set up somewhere. And while clearly those are different things, they’re not as different, maybe, as we once thought. I think that’s an important point, and that’s something where our research is starting to hone in on a little bit, particularly over these next few years as our advances in ctDNA and CTCs come to pass.

Pallav Mehta, MD [00:05:35]

Richard Feynman, who’s a Nobel laureate theoretical physicist, said, “Although we humans cut nature up in different ways ... The imagination of nature is far, far greater than the imagination of man.” Again speaking to this arbitrary nature of these divisions that we make. By no means am I putting myself in this category, but I wanted to share that quote.

So that’s a line that I used to put, until last year, in my notes. We dictate our notes. Wvery time we see one of you, we dictate the office visit. And that line was in all of my office visits for metastatic breast cancer. I would say that I had a long conversation with Ms. So-and-so about the implications of metastatic disease and the goals of therapy, which were not to eradicate, but to control and stabilize. I took that line away last year because I think it was a bit nihilistic as we advance. So that’s it, that’s my soap box on that. But an important one.

Why bone? What is it about breast cancer cells that go to bone? As I said, it’s not all of them. William Paget’s theory was the “seed and soil” theory from 150 years ago. The seeds are the breast cancer cells. For the soil: We think what happens in some cancers, breast cancer, is that the tumor sends out signals into the circulation that go to certain places, bone for example, and then it creates an environment. Whereas those cells that are floating around, those CTCs floating around, they then are attracted to that area. Those circulating tumor cells seem to have these little sticky substances that allow them to stick to the inside of the blood vessel, kind of burrow their way in, so to speak. That’s how we think these metastases happen.

It’s why we think not all cancers go to all organs. For example, colon cancer, it’s not that it never happens, but colon cancer to the bone is really unusual. Estrogen-positive breast cancer to the brain, it’s not that it never happens, but again, a lot less common than, say, a HER2-positive or triple-negative breast cancer. So there’s this predilection, we think. The tumor sends out signals to make the area hospitable for those cells.

A bone is a unique organ. Unlike other organs, it’s constantly remodeling. There’s two types of cells in bones: There’s osteoblasts and osteoclasts. The blasts are the ones that make bone. The clasts are the ones that destroy bone. And those are often in equilibrium. Now, for example, in someone with osteoporosis, they’re not in equilibrium because there’s a breakdown so there’s more osteoclast activity. This is important to understand when we think about how we support women with bone metastases, and the treatments and the supportive treatments that we use.

You can see here the three types of metastases. There’s the blastic metastases. Again, not all bone metastases are the same. Blastic metastases are the ones where there’s more osteoblastic activity. Breast cancer, by the way, kind of has both, potentially more lytic than blastic, but not necessarily. Prostate cancer, for example, is almost a hundred percent blastic. And this gets to our imaging, which I’ll talk about in a second, and the types of imaging tests. But that’s a blastic on my left, a mixed one in the middle, and then the lytic one, you can see, is the one where it looks like the bone is almost like chewed through.

What are the signs and symptoms? Obviously, sometimes it’s incidental, especially if a woman already has metastatic breast cancer. We’re doing imaging tests, and sometimes we just find something that we weren’t expecting. But in the folks that have some sign or symptom, these are the most common.

Pain, by far, is the most common, and 70% to 80% of women with bone metastases present with some sort of pain in that region. It doesn’t have to be a large metastasis to have pain, and vice versa. Sometimes large metastases don’t cause pain. It just depends on the pace, depends on the cortex of the bone — there’s a lot of variables in terms of why someone gets pain.

Pallav Mehta, MD [00:10:07]

Malignant hypercalcemia. In lytic lesions more than blastic lesions, as the bone gets sort of chewed through, you literally get destruction of the bone tissue. And so calcium gets leached into the blood. Now it generally happens in anyone with lytic metastases, but to get to malignant hypercalcemia, you need a lot of it. And so the calcium levels start to rise. When calcium gets to a certain level there’s all sorts of issues that can happen that are potentially very dangerous. But about 10% to 20% of women have that. Thankfully only a smaller portion have a spinal cord compression. We think about 10% of women.

Anything above L2. You have your cervical, thoracic and lumbar spine, and sacral spine. L2 is where the spinal cord ends. When there’s a lesion above L2, especially if it’s a lesion that’s going backwards, posteriorly, towards the front of the body, it can compress the spinal cord. And that is an emergency, for obvious reasons, and requires emergent treatment.

Fracture. About 20% or so present with some sort of fracture. Obviously, most patients with fracture will have some sort of pain.

These are just examples of the different tests that we have that diagnose bone metastases. You have X-rays. I know X-ray sometimes sounds so simplistic, but if you talk with orthopedic oncologists — and most of the big centers have excellent orthopedic oncology departments — X-rays can be really helpful in determining what to do about the metastases and the extent of that metastases.

Bone scans and CT scans, the next two, are the ones where I think most patients with metastatic breast cancer end up getting these two tests to monitor their disease. Bone scans, I’m not so sure are necessarily the best for many metastases. Sometimes they miss things, but they’re easy to get, most centers have them, and insurance covers them. That’s a bone scan there. You can see some of the darker areas are the bone lesions. CT scan is really great for anatomy, particularly for orthopedic oncologists. If there’s any procedure that’s needed, CT scans are usually the way to identify where to go. MRIs are the best anatomical tests and are best for nerve issues. When you’re looking at nerve impingement somewhere, particularly like the spinal cord, MRIs are the best.

Then there’s the PET CT scan. PET CT scans are different from CT scans because the PET is a functional test and the CT is an anatomic test. Essentially it’s like if you have you and a cardboard cut out of you next to each other, a CT scan’s a photograph of that. It can’t tell the difference. A PET scan is a photograph that tells the difference and knows that you’re alive because those cells are doing something. That’s the idea. But again, PET scans can also overcall any activity because not all activity on a PET scan is cancerous.

This sounds obvious, get a biopsy, but you’d be surprised how sometimes we make assumptions. And we never want to make assumptions, especially in this day and age where the treatments are so nuanced and the potential implications are so significant. If a woman has a localized cancer, and for x, y, or z reason, we image that woman and find something in the bones, we do not want to make an assumption that it’s metastases until we get a biopsy. That’s because number one, we want to prove that it’s cancer. I think most oncologists who’ve been doing breast cancer have cases where we thought it was cancer and we biopsied and it’s some benign thing. There’s these eosinophilic granulomas and enchondroma sarcoid of the bone sometimes shows up. That sarcoid is active on a PET scan. So again, don’t assume without a biopsy.

You also want to know, is it breast cancer? Again, I’ve had cases where it’s a different cancer. It’s not common, but a biopsy will help with that. And then, if it’s breast cancer, is it the same receptor profile? We think 10% to 15% of the time that actually can change. So for lots of reasons, if it’s feasible, we don’t want to be sticking needles into dangerous places. But if it’s feasible we should try to get a biopsy.

They’re done in two ways. It’s either an interventional radiologist, usually it’s an interventional radiologist, usually using CT guidance, putting a needle in that bone and getting an answer. Sometimes it’s in a tougher area and an orthopedic oncologist needs to get a surgical biopsy.

Pallav Mehta, MD [00:15:03]

When we think about treatment. You can see the factors, the different variables that determine how treatment would go with bone metastases, and on the right you can see the goals. What sorts of things determine response? What sorts of things determine how long a certain treatment might work? If it’s bone only, versus bone plus visceral, it can be a different type of biology and behavior. Not always but it can.

Oligometastatic. That’s a term I think many of you have probably heard. We don’t have a clear definition for that, by the way. Oligometastatic just means not very many. It can be one, it can be five. In some studies oligo mets are up to 10 to 15. It depends on how the study defines it.

Pace of progression, that’s important. If a woman, if a 70-year-old woman had breast cancer 10 years ago and then we find a couple of bone lesions, that’s a different situation than say a 30-year-old who had breast cancer last year where we find these lesions. We know biologically those are probably different.

Receptor profile, genomics. Remember genomics and genetics are different. Genomics is the cancer’s genes, genetics is your genes. Both have implications but those are very different things. And then how a patient responds to treatment. If a woman has bone mets and it’s 5 years later on the same treatment and it’s been working and then there’s a change, that’s a different biology than someone who, for example, never responded to that first treatment.

Then our goals. That first one there, prevent skeletal events. Those are called skeletal related events, SREs. Many clinical trials around bone lesions, particularly the trials that look at supportive treatments for bone mets, use SREs as an endpoint. So SREs are skeletal events like fracture, pain, need for radiation, those sorts of things. That’s an SRE. And often it’s an endpoint when we think about the benefits of things like bone agents, the bone supportive drugs. Then, of course, improving quality of life: pain, function, emotional well-being, and cancer control.

The first thing I’ll mention is radiation. I hope there’s no radiation oncologist in the room because I will not do it justice. These are $50 million machines that do all sorts of fancy things. But here’s the simplistic, medical oncologist understanding of radiation.

When do you radiate? I think a lot of women will ask us when they come in with these sorts of things, “Why can’t you just radiate them? There’s four or five, why don’t you just zap them?” And I will say that, a few years ago we said that, no, we wouldn’t do it. I liken it to the concept of a forest fire. You don’t go after the tree that started it or the future, you go after the whole thing. However, there is data now that maybe radiating a few or more of these may actually have a real impact on outcomes. So, stay tuned on that, that story is evolving.

But the main reasons to radiate: Pain is by far the most common reason to radiate. And how much pain, again, that’s a subjective thing. If it gets to the point where a woman is on opioid medications, probably radiation’s going to be helpful. If the woman doesn’t really need much, maybe takes an occasional Tylenol, then we’ll keep her on the treatments that she’s on. Maybe switch the treatments, to a new treatment to see how it works. There’s all types of radiation. I’m certainly not going to get into the particulars of that. But you can see here EBRT stands for external beam. That’s kind of the standard radiation, and that’s the one where you get five to 10, we call them fractions.

By the way, I don’t know if you know, we call them fractions because in the old, old, old days, the 40s and 50s. When we weren’t sure how radiation actually did its thing, they often gave these huge single doses, which yeah, it helped the cancer but often really didn’t help the patient because of the side effects. So we fractionated out the dose. Now when you think of 10 doses, you’re not getting 10 doses of radiation. What you’re getting is one dose that’s split into 10. So that 10th dose becomes the final brick in that wall. And that’s how you want to think of fractions.

SBRT stands for stereotactic body radiotherapy, essentially a more targeted beam of radiation to a specific area that can be done in three sessions. More recently we’re starting to see in specific areas where it’s safe to do, where the lesion is not very large, a single fraction. They give a lower dose, but it’s a single fraction right to that area and it’s found to be just as good and maybe in some places even better than multiple fractions. But again, that’s up to the machines and the radiation folks.

Procedural, there’s a lot here. Procedurally, what are the things we can do? Surgical. I’ll say again, if there’s any surgical need for a bone lesion, an orthopedic oncologist, if at all possible, should be the one dealing with it. Granted, some folks live in parts of the country where there isn’t access to orthopedic oncology — they’ll usually be in academic centers. But I can tell you just from experience and from having patients who’ve, you know, it’s not that orthopedic surgeons aren’t great surgeons, it’s just when you’re not trained in how to do these surgeries for cancer patients, they can sometimes not be done exactly the way they’re supposed to, especially with the larger lesions like hip replacements and those sorts of things. So orthopedic oncology if at all possible, even if it’s for an opinion.

Pallav Mehta, MD [00:20:56]

What do they do? All sorts of things. Rods, nails, screws. Our orthopedic team recently had a patient who’s a metastatic breast cancer patient with such extensive pelvic metastases that she probably had four or five different fractures and her pelvis looked like it was in a severe car accident. She couldn’t walk, she was in pain all the time. And so our surgeons did, similar to this photo, they have these screws that actually curve through the pelvis. They can curve them how they want. Then it just tightens once it curves, and it sits. So he was able to repair her pelvic fractures, all of them. Two days later she was actually able to walk, and her pain was down. Yeah, it’s amazing. This is why it’s good to have subspecialists.

But what’s the goal for them? Decreased pain, obviously, increased function. Nonsurgical procedures, there are many. RFA and cryoablation. RFA is radiofrequency ablation. Cryoablation is using freezing techniques. Those are used if there’s a very small lesion. I think they’re used a lot less now because of SBRT and our ability to do single fraction treatments. So that’s becoming less and less common.

I don’t want to forget kyphoplasty. Kyphoplasty is something that’s been around for a long time and still can be a very useful thing. Kyphoplasty is a specific procedure. You can see the photos there. Essentially it’s for spinal lesions. Sometimes what happens is, when there’s a cancerous lesion of the spine — by the way, these aren’t only done for cancer, they’re also done for osteoporotic compression fractures. A compression fracture meaning the vertebrae compresses. And when the vertebrae compresses, you tend to compress the nerves that come out of that vertebrae. That causes a lot of pain.

What they do in a kyphoplasty — neurosurgeons, orthopedic surgeons, and interventional radiologists can do it. They put a needle in there with a balloon, they blow up the balloon that opens the height, that brings the height of the vertebrae back, and they inject essentially cement or cement-like structure that keeps it up there. And it can be magical for pain relief in the right patient, in the right situation. In lumbar lesions, those weightbearing areas where the curvature of the spine is causing the pain, it can be life changing.

Then the osteoclast inhibitors. This is the domain of the medical oncologist. Osteoclast inhibitors essentially come in two types. There’s the bisphosphonates, which are the ones that have been around for a long time, the original. There’s the old oral ones like the Fosamax, or alendronate, risedronate, those sort. There’s other newer oral ones. There’s intravenous ones like zoledronate, or Zometa.

Then there’s denosumab, which Xgeva is the trade name for it and Prolia when it’s used for osteoporosis. They are still osteoclast inhibitors. They just inhibit the osteoclast differently. So remember osteoclasts are breaking down bone. So if you inhibit the cells that break down bone, you allow the bone matrix to then remodel so that the cells that build bone back up are supported.

A few things with those. You do have to take vitamin D and calcium when you’re on these, we sometimes forget to tell patients about that. Any of those drugs can cause low calcium. So taking just a little bit of, not a lot but just a little bit of supplemental calcium is actually important along with vitamin D.

I just mentioned this one side effect — I apologize for the more graphic photo — but this is something that I think patients think about a lot because they’ve heard about a lot. It’s now called M-R-O-N-J. MR stands for medication related. ONJ stands for osteonecrosis of the jaw.

Pallav Mehta, MD [00:25:00]

Osteonecrosis of the jaw is this condition where there’s essentially a breakdown of the bone. We think there’s some infection related, we’re not exactly sure why these drugs do it, but it is a potential side effect. It varies in different patients. So the overall incidence in metastatic breast cancer seems to be about 1% to 2%, but the frequency of treatment matters. In the women getting monthly, there does seem to be a little higher risk. We think, for many patients, actually every 3 months, they’ll probably be fine for these drugs. I know most patients get them monthly. But even if you’re getting it monthly, we think maybe no more than 2 years monthly and then start backing off to every 3, 4, 6 months. No one really knows exactly the time. Basically the idea is less of it after you get at least 2 years. Some centers use 1 year of monthly and then less frequently.

Make sure to talk to your team about that because sometimes I think we overuse these drugs. If a patient has a single, a couple of bone lesions that aren’t in weight-bearing areas, not causing any problems, then we put them on monthly Zometa. Maybe that’s a little overkill.

The big thing to remember with these drugs is the dental work issue. Avoid invasive dental procedures around the time of the shot. Invasive means anything involving the jawline. Extractions or implants are your big ones. Root canals are fine. It’s just when the actual jawline is involved, there is an increased risk.

My rule of thumb is 6 to 8 weeks. I’ve seen across the board. Some people say 3 months, some people say 4 weeks. The big thing I think that I’ve learned is after an extraction or implant, I always want the dentist or oral surgeon to see the patient back to confirm. Because I thought that a clearance was enough, but a couple times there was a problem that just wasn’t noted. And then I gave a drug and then osteonecrosis happened. So I think seeing them back for visual inspection of that area 6 weeks later to make sure, that’s an important thing that I’ve learned.

Then every 6 months treatment, I mention this because of the drug Prolia or those getting Zometa every 6 months, it’s almost negligible that risk when you get to the 6 month dosing. Dosing frequency matters.

Signs, symptoms, labs, imaging.

Signs, symptoms, labs, imaging.

These are the four ways that we monitor metastatic cancer. Metastatic breast cancer: signs, symptoms, labs, imaging.

Signs are things we find on you. Symptoms are things you tell us. If you have pain, that’s a symptom. But when we find tenderness, that’s a sign.

Signs and symptoms are important. They’re sometimes more important than labs, but labs are a part of it. Labs like alkaline phosphatase, it’s one of the bone enzymes. It’s also a liver enzyme, so you want to know which one you’re dealing with. Calcium levels. Tumor markers. There’s a lot of debate about tumor markers. Should we check them? Should we not? We think in bone lesions, particularly in women where the marker is elevated at diagnosis, it actually is helpful because bone lesions are historically hard to follow. So the marker is like an adjunct, it’s an additional thing. We do not use tumor markers in a vacuum. They can go up and down for reasons having nothing to do with cancer. That’s an important thing to remember.

We can have a whole other conversation on ctDNA, but that’s for another time. In a couple of years I’m sure that’s something we’re going to be doing a lot more of.

And then imaging. You can see more sclerosis, you can see less activity on PET scan. On the left, you can see those lesions, bone lesions. On the right, you can see they disappear. Except it’s the opposite, and you didn’t realize that. Where you think you’re seeing bone lesions, that’s actually the treated scan. That’s called sclerosis. Where you think you’re not seeing them. Where the spine looks nice and clean, that’s where the bone metastases are. A word of caution if you see these sorts of images. Sclerosis is actually a good thing. That means that bones are healing. Tricked you.

A couple of words from an integrative oncology standpoint. Calcium is important. Not too much. We used to tell women, I remember years ago, take 2,000 milligrams a day, and then we realized that wasn’t good for various reasons. At least 500 milligrams a day is going to be important. Especially because most women with bone mets are on these drugs, these osteoclast inhibitors. Dietary calcium — as you know with most of these minerals and supplements, if you can get it in the dietary form, you’re going to absorb it better.

Pallav Mehta, MD [00:30:00]

It is important to know you can only absorb about 400 to 500 milligrams at a time, whether it’s a supplement or in a diet. If you’re having your yogurt and granola in the morning, don’t take your calcium in the morning. You’re going to waste a lot of it because you can only absorb so much. Split up your dosing.

Vitamin D3. When it comes to bone lesions, checking your vitamin D3 level is important. Unfortunately, Medicare recently said no to approving vitamin D levels, so we’ll see what happens with that. But vitamin D, you can check a level every now and then. You don’t need to do it all the time, but maybe twice a year. Keeping it normal, which is above 30, we think a little above normal maybe with bone lesions, in that 30 to 50 range.

But just like anything, there is a therapeutic window. Above 80 you’re going to start to see toxicity. When vitamin D gets too high, it will start to leach calcium from bone. It’ll start to increase absorption from the gut. You can have increased calcium in the blood. Kidney stones are one of the more common things we see. I had a patient a few months ago with that exact scenario. She was on very high doses of vitamin D from a different provider, but her levels weren’t being checked. Her level was 230, which is the highest I’d ever seen. And she had kidney stones from it. She’s fine now, thankfully.

There’s some other minerals there. Magnesium, zinc. We think magnesium might help calcium get into the bone matrix a little better. Zinc, we think has some value. Vitamin K2, most people do not need. It helps you absorb vitamin D better. I think about 5% of patients actually need it. Boron is another one that’s been looked at in bone health.

Mind-body practices, the ones I mention here, mindfulness, acupuncture, even yoga done gently. There’s value in terms of function. There’s value in terms of emotional health. There’s value in terms of pain. There’s actually some data on acupuncture and pain management that’s interesting. So it’s a supportive type approach that can be used on top of everything else that you do.

I will mention, about exercise. Before I was in medical school, I was a personal trainer for 2 years. So exercise has been something that I’ve tried to incorporate into my life and I try to recommend for patients. But exercise means different things.

Resistance exercise is one important type of exercise that everyone should be doing. I think there’s always this worry that if there’s a bone metastases, it’s going to break, it’s going to fracture, so god forbid you do anything. Obviously you need to speak to your team and make sure that in areas that the lesions are treated.

If you’re on treatment and it’s going well and your lesions are treated, you can do some gentle resistance exercise. You’ve got to be careful how you do it. We know it’s important for bone density, muscle mass. It’s also important for strengthening the tendons and ligaments around that muscle. It’s not just about the muscle and bone.

It improves appearance. Sort of dismissively, we say it’s cosmetic. I don’t really think it’s cosmetic. There’s a difference between identity and vanity, and I think having muscle and improving appearance and how you look in the mirror, it helps for so many reasons that I don’t have to tell anyone else here in the room. But I think that’s an important part of exercise, resistance exercise.

You want to be cautious around the weight bearing bones. The photo on the right, the spine, is a compression fracture. On the left, that’s a fracture in an important area that we worry about when we see it. That’s called a femoral neck. You hear about an older person who might’ve fallen and broken their hip. They don’t actually break their hip. What they break is this. The femoral neck is the little area of bone that connects the head of the femur to the actual shaft of the femur. It’s a smaller area. When we see a lesion in the femoral neck, that’s an area that gets an immediate orthopedic surgical consult about what to do. Should that be fixed or not? Should that be radiated or not? So you want to know before you embark on some sort of resistance exercise where your lesions are and are they in weight bearing areas or not.

You also want to make sure, if you are going to do this, that you have somebody who knows more than just ... You don’t want a meat head is the bottom line. Although not all meat heads are terrible. There are a couple of organizations. I was certified through the American Council on Exercise. They have a special certification for trainers once they’ve had a thousand hours of work to get cancer certified. Same with the American Council on Sports Medicine. You can go on their websites, find trainers who have this extra level of certification so they don’t hurt you when they’re doing their workouts.

Pallav Mehta, MD [00:34:58]

And cardiovascular exercise, what is it? First of all, it’s an intentional activity with sustained duration, heart rate greater than 60%. That’s my add-on. Heart rate greater than 60% of your age-predicted max. Lots of formulas on how what that is, but essentially the old formula still works. Your age-predicted max is 220 minus your age. Generally speaking, in someone of regular conditioning. So 60% of that, you’re in the cardiovascular exercise range.

High impact, you want to be very careful about. You can have cardiovascular exercise without impact. Riding a stationary bike. You can get your heart way up. It’s not impact. High impact means both feet are off the ground at the same time. Running is high impact. Jumping. Those things you want to be very careful about with weight bearing lesions.

Cardiovascular exercise increases fat loss. Remember in postmenopausal women, which most women with metastatic breast cancer are going to be postmenopausal because if they’re premenopausal, we make them postmenopausal. And if they’re not, they’re already postmenopausal. We know that when a woman’s ovaries go to sleep, fat cells take over. That’s how you make estrogen. Fat cells turn one of the testosterone precursors into estradiol. Aromatase is the enzyme that does that, and that’s why we block aromatase. But when there’s less fat cells, less estrogen. There’s evidence that less fat cells, less estrogen makes aromatase inhibitors more effective.

Exercise also helps decrease your vasomotor symptoms, those are the hot flashes and night sweats, and joint pains. Even patients with arthritis, we know exercise helps. Cardiovascular exercise helps.

I just mentioned this intervals thing. I said earlier that you want to be gentle, you do want to be gentle, but if you work your way up, anyone can do interval exercise. The intervals that I prefer what I put up here, which is these heart rate intervals, that’s different from time and distance. Most people have heard about intervals as you do a minute of this and then 3 minutes, or less, of that. Or you do a mile here, you do half a mile here.

Heart rate is the most individualized way to do intervals. You need something, whether it’s a watch or a device or just the handheld bars on a treadmill. The idea is you have to know your window. Your upper heart rate, let’s say is 140, your lower, your floor, is 110. You stick in that range. You stay at your upper, 140, for 30 seconds, a minute, then you back down until your heart rate gets down to your floor and then you go right back up.

That kind of interval training is just really individualized to the person because it allows them to recover in the way they would recover. Triathletes are going to recover very differently than sedentary individuals. My daughter, who’s 23, is a rower. She just told me that yesterday she did six 800s around the track in 60 seconds, and she rested and her heart rate went down 50 beats. That is not normal. If your heart rate can go down at least 20 beats per minute in 1 minute you’re in pretty decent cardiovascular shape. That’s a good way to tell. Beta blockers aside by the way. Not being on medications that inhibit that.

Finally, balance and coordination. This is something I think that’s occasionally ignored. How do patients with bone metastases break bones? Sometimes it happens spontaneously, but falls are a very common way. Falls can be limited, especially in older patients, with some sort of balance work. There’s something called vestibular physical therapy. It’s something I actually recommend a lot for my older patients with bone lesions. You’d be surprised how your balance and your sense of where you are in space and where your limbs are in space can be affected as you get older. Doing vestibular therapy can really be valuable.

One thing that I personally have started recommending to a lot of patients is a weighted vest. It doesn’t have to be a lot of weight, but it’s a way to get resistance exercise and balance work without any additional time in your day. If you’re going to walk your dog anyway. If you’re going to go for a walk anyway. If you’re going to go to the grocery store. Though it looks a little strange in the grocery store, like you’re wearing a SWAT team vest. But it’s a way to get extra exercise and not even think about it. So weighted vest, look into the options there. And that’s all I got. Thank you.

Caroline Koffke, RN, BSN, OCN [00:40:00]

Thank you so much, Dr. Mehta that was absolutely wonderful, and we have so many wonderful questions from our audience for you. Keep them coming because we will continue to ask them. But one that I’ve seen quite frequently is about preferred imaging.

I know you talked about PET scans, bone scans, CTs, and even the value of an X-ray, which was very informative. Do you have a preferred imaging for tracking bone-only disease? And caveat, can you also talk a little bit about the Cerianna PET?

Pallav Mehta, MD [00:40:34]

It’s hard to say one imaging is necessarily preferred. I do like PET CT scans. Particularly when I’m assessing response, when you see activity in a lesion and then you stop seeing that activity, potentially you have a pretty good idea that something is responding. It’s not always perfect because sometimes there’s false positives in other areas for various things. But of the sort of regular testing, I tend to get PET CTs.

I am in the minority. I think partly I’m in the minority because the dirty little secret is we don’t want to argue with insurance companies anymore. I hate to say they won, but I think with the number of phone calls, we just don’t have the time anymore. I think that’s an unfortunate thing, but CT scans and bone scans tend to be the common testing because of that. Most clinical trials use CT and bone scan as well. So that’s another reason. But if you see anything on a CT that’s questionable, then a PET CT can really help you.

Cerianna PET, which Cerianna is the brand name. For those who don’t know, that’s known as an FES PET. That E is standing for estrogen. Your standard PET scan is you have glucose that’s tagged to a radioactive molecule. The idea use the Warburg effect, that cancer cells, as they grow and divide, they have to take up glucose to divide.Not just cancer cells. All cells generally do that, but as cells that are more rapidly dividing take up more glucose, when you image it, you’ll see more activity there. That’s glucose.

The idea behind an FES PET is that estrogen is now the molecule that’s tagged to the radioactive substance. So wherever that goes is where you’ll see activity. I can’t say I’m an expert on FES PET. I’ve used it recently in specific scenarios. I had a patient recently, actually very interesting, a woman with bone metastases who, on her recent PET scan, we saw two new lung lesions, and they were visible on CT as well. They didn’t make sense though, given how everything was going and everything was so stable, and all her markers, everything was normal. She had this questionable upper respiratory thing, and so we could have dismissed it as that. She was worried about waiting for another 2, 3 months to get another scan. So we got an FES PET, and they were completely normal.

Is it possible that they weren’t estrogen sensitive? So there’s questions around that. But it was helpful in her case because it turned out they really were nothing. Eventually they did disappear. So there’s certain places where I think we can use them.

Stephani St. Cyr [00:43:20]

You talked a lot about supplements and things like that, and I want to know this. This is personal to me because I’ve heard it so many times. Creatine. Is that good? And does it actually give you a better quality of life? I’ve heard some people say no, some people say yes. I want to know.

Pallav Mehta, MD [00:43:42]

To answer the question directly: Is it going to improve your quality of life? Probably not quality of life.

However, creatine is safe. Most studies have shown that, and creatine’s been around a long time. I remember in my early twenties taking creatine. We have a lot of years of data on creatine. You need to take inordinate amounts for it to be unsafe. Five grams a day it’s fine to take. It supports muscle growth. I think for patients particularly who have some atrophy, I think it’s a really interesting thing to use.

What happens with creatine though, is the folks who are taking creatine also tend to then take higher amounts of protein powders and other things. Too much protein can be dangerous for your kidneys and those sorts of things. But five grams of creatine a day, I think is a very safe thing for most patients. But the disclaimer is talk to your doctor.

Caroline Koffke, RN, BSN, OCN [00:44:42]

Can you talk a little bit more about pain management? Maybe some strategies you have used with patients who may have increasing pain from bone mets involving potentially palliative care. How do you work with that team? Or what suggestions would you have for someone who has a good deal of pain from their sites?

Pallav Mehta, MD [00:45:00]

I definitely work with palliative care a lot. I’ve been one to introduce palliative care early in the management of metastatic breast cancer.

We have to get away from this idea that palliative care is hospice care. It clearly is not. The reason [for the confusion], partly, is that a lot of the training is combined. Palliative and hospice. It’s a combined training. The directors of palliative care are often the directors of hospice care. So it’s often confused with each other, but they’re very different.

Palliative care I think is an important aspect of management for anyone with metastatic cancer, particularly early on. Because when you’re in with the team, you can have conversations about things that could develop, that are starting to develop, so you cut things off at the pass. Our palliative care teams have been great at helping us manage pain.

Outside of pain management docs and maybe rheumatologists, oncologists are generally well-versed in the management of pain. For those who have seen the movies on Purdue Pharma and all of that, I specifically remember getting visits about conversations around “Just give this much,” and “Give this much. Don’t worry about it. There’s no addiction.” I remember those visits very well. But we know that opioids can have a place in the management of pain if it’s done correctly. Lower doses. Obviously the goal is to try to get someone off those. But low dose opioids in the management of pain with some anti-inflammatories can be a great way to manage.

There are some supportive strategies that can be used around pain management. Acupuncture sometimes helps with neuropathic pain as well. It’s about the types of pain. Is it inflammation? Is it nerve? Is it skin?

There’s lots of different approaches to pain management, but I generally get my palliative care team involved.

Stephani St. Cyr [00:47:07]

Why do some mets show on the bone scan and maybe not on a PET scan and vice versa, because that has happened to me. It showed on one but didn’t show on another.

Pallav Mehta, MD [00:47:23]

It’s a great question. I’m not a huge fan of the bone scan for that reason. If you remember, I put up the image of a blastic and a lytic. Bone scans are really good for blastic metastases. A prostate cancer, that’s actually the standard test. because you can really see things well. Lytic lesions aren’t always seen well at all. Sometimes completely missed. Many patients have had that experience where a bone scan will see nothing or almost nothing and then a different scan sees a lot more. But that’s why; it’s the type of metastasis.

Caroline Koffke, RN, BSN, OCN [00:48:02]

We have some questions about massage and chiropractors. Is that safe? I know you probably have a disclaimer there, but what are your thoughts on using massage or going to a chiropractor with bone mets?

Pallav Mehta, MD [00:48:14]

So they’re two different things. Massage, if you’re going to a masseuse, just like in personal trainers, masseuses have an opportunity to get specialized training in oncology massage. I think if you’re going to a specialist, someone who knows, then massage is generally safe.

If you’re in a situation where there’s a bone that’s close to potential fracture, you probably already know it by now, especially if you’re being watched. I think oncology massage generally safe.

Chiropractic, I don’t know that much about it other than some scary TikTok videos that I think we’ve all seen, which I would not recommend those things. But I don’t know. I haven’t seen much evidence of benefit in our space. Not knowing enough about it, I don’t know if they would potentially increase fracture risk in some areas. There might be some benefit in other areas. I don’t know if I could give you a smart answer on that.

Stephani St. Cyr [00:49:24]

I have one more question. As we know, breast cancer does not discriminate. If you are male, if you’re female, if you’re Black, white, purple, orange, it doesn’t matter. So, one question here is, do you have any additional treatment advice for males diagnosed with MBC?

Pallav Mehta, MD [00:49:45]

So 1% of all breast cancer is in men. I’ve treated men over the years. Because they represent such a small percentage of patients, we don’t have male-specific clinical trials. It’s really hard to get enough men with that condition to be in a study, especially if you’re talking about a few centers. Most of the evidence we have is extrapolated from women.

Male breast cancer really becomes a very individual kind of thing. It does appear that there’s more estrogen positive in male breast cancers. It could just be the absolute numbers are less, so we’re not sure. But we treat male breast cancers somewhat similarly, there are some exceptions: certain medications tend to work better in women than men and how we manage suppressing testosterone. Testosterone is a feeder to estrogen. So some of the endocrine and hormonal approaches tend to be slightly different in men. But for the most part, most of the treatments are very, very similar. At least that’s how we practice.

Caroline Koffke, RN, BSN, OCN [00:51:00]

You mentioned a lot of really great information about radiation, lots of questions about that. Is there a place for radiation without pain? Is the radiation actually killing those cancer cells? Is there a recommendation, again, to get radiation done if maybe you’re not in pain?

Pallav Mehta, MD [00:]

That’s the evolving question right now.

I would say right now the standard is still, we’re not just radiating something if there’s no other symptoms. The exception could be a very small amount of bone lesions. If there’s one or two lesions, should we consider radiating them? We don’t have the data that says yes yet, but it’s this question of what an oligometastatic bone-only patient is. Are we really impacting that patient’s outcome? Intuitively, it sounds like we should, but remember that cell got to the bone in different ways. It didn’t just hop over there, it got there through the bloodstream. So there are still cells in the blood.

The difference today is that our systemic treatments are so much better. Broadly speaking, we’ve started to look at local therapy in metastatic breast cancer differently today than say 10, 20 years ago when it was heresy to consider local therapy. Today, again, you look at HER2 positive, for example. Our treatments just continue to get better and better. We really are starting to think about local therapy differently.

What was the third part of that question? Did I answer that?

Caroline Koffke, RN, BSN, OCN [00:52:45]

Just if it actually is killing the cancer cells.

Pallav Mehta, MD [00:52:47]

Yeah, so it is killing the cancer cells, but for the most part, you don’t want to look at it that way. It’s generally done because there’s something going on there that needs to be radiated, because there’s a symptom or something. It is killing the cancer cells. That’s definitely what radiation is doing.

Caroline Koffke, RN, BSN, OCN [00:53:07]

Thank you. Another question: Can you recommend a good calcium or vitamin D supplement? I know you were talking about particular dosages. Is there any specific brand you recommend or can you just review those dosages again?

Pallav Mehta, MD [00:53:18]

I don’t endorse any specific brand. I don’t sell anything. If I did I would endorse it.

Maybe I’ll just mention broadly when it comes to supplements. I get asked this a lot, “I want to take this probiotic or this, which brand?” There’s a thousand, or actually probably more than that, brands out there. So it’s really tough to know which one to take. And by the way, it’s not like one is the best.

What you want to be careful of with supplements is, as you know, they’re not FDA regulated. So it is a bit of the wild, wild west in terms of the dosing. A label can say a thousand milligrams, but the actual dose can be 500 milligrams. And that’s absolutely happened. How do you avoid that? How do you avoid contamination?

One of the ways to do it, there’s three independent nonprofits that the supplement manufacturer would have to voluntarily submit their product to — so again, voluntary — that tests the product for whether there’s contaminants and whether the dose on the label is the dose in the bottle. You look for one of those three labels, and those are:

The USP. That’s the US Pharmacopia. If you see a USP label, common supplements that you sell at CVS, like Nature Made has that.

NSF, which is the National Science Foundation.

And then CL, which is Consumer Labs.

If you see any of those three labels, you at least know you’re getting a product that has been tested. It doesn’t mean that products that don’t have those are bad, it’s just they may not have submitted their, you know, supplement. One thing to remember, for the most part, you do not have to pay an arm and a leg for supplements. Most supplements, particularly those, tend to be the less expensive ones and can be just as effective.

Dosing for vitamin D. You should check a level if you’re going to take vitamin D, at least once to know what your levels are. Because you can overdose on that. Dosing should be based on your levels when it comes to vitamin D.

Calcium, we know that for most people, the maximum should be about a thousand milligrams a day. How you take it — calcium carbonate, calcium citrate. Citrate tends to be absorbed a little better. But I think those are negligible differences. But that’s the kind of dosing of those.

Stephani St. Cyr [00:55:50]

Another question. What are your thoughts on massages with bone mets when there are so many lesions? Is it is good? Is it bad?

Pallav Mehta, MD [00:56:06]

As I said about the massage, I think a good oncology masseuse that sees you would want some information on you before they perform any anything on you. I would look at it as I defer to the expertise of those who do it.

As long as you’re going to someone who has an oncology certification, I doubt they’re going to be doing deep tissue on folks who might have that.

Caroline Koffke, RN, BSN, OCN [00:56:36]

A few questions also about weight loss drugs. Obviously those are big in the media right now and you talked a lot about weight loss.

Pallav Mehta, MD [00:56:44]

We got about 3 hours here?

Caroline Koffke, RN, BSN, OCN [00:56:45]

Exactly. How much time do we have?

What are your thoughts on using that, especially maybe to decrease estrogen? We’ve had a couple questions come in about that.

Pallav Mehta, MD [00:56:58]

By weight loss drugs, of course we’re referring to the GLP-1 agonists, which are all the rage. There are, by the way, 65 GLP-1 agonists in clinical trials right now in various companies. Orals, the first oral probably comes out the end of this year into next year. There’s now muscle sparing GLP-1s that are going to come out another 2 years. So this story is evolving a lot.

I think the concern with GLP-1s in metastatic cancer is that you want to be very careful how you dose them. When they first came out, patients were just ramping up doses and they were getting that serious gastrointestinal problem. Some patients got gastroparesis, total slowdown in their gut even when they went off of it. We’re not seeing that much anymore because we realize the dosing needs to be slow.

I think the weight loss that’s happening right now with most GLP-1s, you’re seeing a lot more muscle. You’re seeing some fat loss, but you’re seeing a lot of muscle loss. The problem with that is muscle is going to be very important as I talked about, because muscle supports bone. It allows you to function. It’s about strength and balance and coordination. Muscle is important for all of that.

There’s probably a place in the individual for certain people, if their BMI is very high. It’s all about the line between the adverse health implications from the weight itself to the adverse health implications from taking a GLP-1. It’s a conversation.

I have a few patients with metastatic breast cancer who are on them at low doses, and they are losing weight slowly. In patients who are on it, any patient of mine that’s on it, I make sure that they’re on some sort of resistance exercise program, and they are out there now. There’s apps now that help you with that, nutrition plans that help you with that. So there needs to be a concerted effort to maintain muscle.

Stephani St. Cyr [00:59:14]

We’ve had questions about bone strengthening meds and things like that. One here is are there any benefits in being on bone strengthening meds like Zometa if the bone mets are no longer there? And then there was one about does Xgeva lessen after time? So that’s kind of twofold.

Pallav Mehta, MD [01:00:02]

The efficacy of it?

I think the question about should you still be on those if your bone mets are healed, it’s an interesting question. What does healed really mean? I think that gets into our ability to image women with bone lesions.

We’ll be able to tell how things are going, based on the various tests. We know that most patients on these eventually, after, 2 years max, we start to lower the amount of how frequently we give it. There are some studies suggesting that we’ve maximized the benefit after 2 years, and maybe we can just stop the treatments.

It’s an individual thing, but if I have a patient who has significant extensive bone metastases at diagnosis, even if her scans, PET scans, are clean and everything looks good, I do tend to continue them at lesser frequency. The idea being there can be changes in the wrong direction at some point. I do look at things like dental hygiene, especially if it’s an older patient who might already have a dental bridge, and some other teeth might potentially need to be extracted. That’s a different patient than say a 40-year-old who there’s no concern about anything like that. So I do think about those risks, but I do tend to keep going at lesser frequency for most of my patients.

Caroline Koffke, RN, BSN, OCN [01:01:34]

Similarly, if someone is unable to be on one of those medications anymore for whatever reason, a fracture afterwards, potentially ONJ, what are your best suggestions? And I know you’ve touched on this briefly, but just to reiterate, what are some of your best suggestions to maintaining that bone health?

Pallav Mehta, MD [01:01:53]

What’s interesting is once you’ve had ONJ, we’re not so sure that continuing the medicine makes anything worse, which sounds counterintuitive, but you’re right, most of us do tend to stop those medicines. It’s really then focusing more on resistance, making sure you’re healthy, making sure you’re balanced, making sure the fall risk is diminished. And then maybe it lessens the threshold for radiation in some areas. If there’s a questionable lesion that you may not have radiated because you just want to wait, maybe that lesion gets radiated. But I think it’s just about supporting your physical functioning and pain management at that point.

Stephani St. Cyr [01:02:40]

I know we’ve been talking about pain and progression and things like that, but does a sudden increase in bone pain typically indicate that it’s progressing.

Pallav Mehta, MD [01:02:54]

If there’s a sudden increase in bone pain, often there could be a fracture. That’s often, if it’s sudden.

That depends on what sudden means. If you’re doing something and it’s like, boom, it’s that sudden, it’s often a fracture, that’s not progression. Or it’s some sort of injury.

If it’s happening over the course of several weeks and there’s worsening pain, that often implies that there’s some progression in that lesion. Not always, but if something like that were to happen to a patient, I generally want to image them to see what’s going on in there.

Stephani St. Cyr [01:03:32]

That was my next question. Should we get additional imaging to find out exactly what’s going on?

Pallav Mehta, MD [01:03:39]

Yeah, remember: signs, symptoms, labs, imaging. Signs and symptoms are really important. I know patients often think about the objective things like labs and imaging. We often think about how you feel. Because that’s important. Because we know when patients feel better, generally things are going better. Generally.

Caroline Koffke, RN, BSN, OCN [01:04:00]

I saw a couple questions come in as well about, we talked about some surgical procedures. Is there a place to remove bone that is diseased or just take it out in that regard?

Pallav Mehta, MD [01:04:13]

I’ll say probably not just removing bone. It’s almost a more aggressive answer to the radiation question. Should we just radiate if nothing else is going on? Surgery is a much bigger deal. It’s very rare we consider a surgical approach to bone lesions outside of an impending, like a fracture risk or something where it’s in a really scary weightbearing area.

Caroline Koffke, RN, BSN, OCN [01:04:49]

Another question also about osteoporosis or osteopenia, especially as individuals age. Do you see a role for a DEXA scan on top of everything else that you’re doing? Or anything else to consider as individuals age if they have bone mets?

Pallav Mehta, MD [01:05:08]

I usually don’t get DEXA scans, and that’s generally because most of my patients are on some sort of bone agent. If you think about the dosing. Most of you know Prolia. Prolia is denosumab. Denosumab is the generic for Prolia; it’s the generic for Xgeva. It’s the same drug. The difference is Prolia is given every 6 months, so twice a year, at 60 milligrams a dose. Your total annual dose is 120 milligrams. Xgeva is 120 milligrams given monthly.

As you can imagine, just following that logic, the likelihood of bone density issues if you’re getting monthly or even every 3 month Xgeva is nominal. And even if you were, there’s nothing more to do beyond that because you’re getting a very aggressive treatment already.

Stephani St. Cyr [01:06:10]

I have a question here, and I’m kind of curious about this myself. Can you address any differences in lobular and ductal breast cancer in bone mets?

Pallav Mehta, MD [01:06: 28]

We often talk about the difference between lobular and ductal cancer. When it comes to metastatic breast cancer, it’s really the cancer itself that will determine it. Meaning whether it’s lobular or ductal, the receptors are going to be important. Lobulars, maybe on the whole are a little more likely to be ER, PR positive, less likely to be HER2 positive. So we’re really managing based off of that. It becomes more relevant in early-stage breast cancer when we’re thinking about surgical approaches and margins and lymph node analyses. Lobular cancers are the sneakier cancers that sometimes we don’t always see on our routine imaging, but that’s early stage. When it comes to metastatic breast cancer, I would say we’re not really, we’re not differentiating it that way.