Protection Against Doxorubicin’s Cardiotoxicity: Exercise?

One of the strongest chemotherapy drugs used for breast cancer is doxorubicin, a drug in the anthracyline family that you might know as Adriamycin. It’s called “The Red Devil” due to its bright red color and tendency to temporarily dye the bodily fluids of its recipient red, but also due to its toxicity.

While it is highly effective, its use is limited by its potentially serious side effects, including damage to the heart. According to Drugs.com, “[b]ecause of its heart toxicity, doxorubicin has a maximum cumulative dose that can be given to each patient. The higher the total dose you receive over time, the greater your chance of heart side effects.”

Doxorubicin is a highly effective chemotherapy, but carries with it a considerable risk of heart toxicity.

There has been interest in discovering other drugs that can decrease the cardiotoxicity of doxorubicin, particularly since in addition to breast cancer, it is used against a variety of other cancers.

But as with so many things cancer-related, the drugs given to protect against chemotherapy side effects themselves have side effects, so it’s useful to explore other means of achieving protection from the toxic effects of doxorubicin.

Can Exercise Help?

In a webinar for the American College of Sports Medicine (ACSM) that I attended on May 18, 2023, University of Florida, Department of Applied Physiology and Kinesiology researcher Dr. Ashley Smuder and her lab presented research about the protective effects of exercise on the heart and muscle doxorubicin.

Importantly, Dr. Smuder’s lab was able to demonstrate that exercise-trained rats who were then given doxorubicin showed a decrease in the amount of drug that accumulated in the heart and diaphragm compared to sedentary rats, echoing the results of Parry and Hayward (2015, Am J Physiol Regul Integr Comp Physiol). Those results had suggested that exercise didn’t diminish and even increased the amount of doxorubicin that made it to the cancer tumor while decreasing the amount of the drug that went to the heart (left ventricle) and diaphragm.

Exercise keeps rodents healthier, even under a punishing chemotherapy regimen.

While the actual mechanism of this protective effect is still being researched, once again these studies show the benefits of exercise in a cancer situation.

Additionally, a doctoral student in Dr. Smuder’s lab, Brendan Nguyen, reported on work that he’s done showing the differences of exercise on fat mass and lean mass in rats administered doxorubicin using the same infusion schedule that a human patient would received (4 doses, 3 weeks apart). There were four conditions: (1) a sedentary group that received saline injections, (2) a sedentary group that received doxorubicin, (3) a moderate-exercise group that received doxorubicin, (4) a high-intensity exercise training (HIIT) group that received doxorubicin.

  • Moderate exercise: rats ran on a treadmill 3 days/week at a speed of 30 meters/min for 60 min/session.
  • HIIT exercise: rats ran on a treadmill 3 days/week, four 4-min bouts at 45 meters/min with 3 minutes of active recovery in between the bouts.

Not surprisingly, the exercise training had a significant effect on the body composition of the animals. Sedentary rats in both groups had an increased risk of obesity. Both groups of exercising rats (both moderate exercise and HIIT) saw a decrease in fat mass during this time and were able to avoid doxorubicin-induced cardiorespiratory weakness. Also, the HIIT exercise animals showed a significant increase in lean mass in addition to the drop in fat mass.

For reliable protection from the negative physiological effects of chemotherapy, exercise is still your best bet.

These findings in rats reflect similar results that have been obtained in humans (Battaglini et al, 2014, World J Clin Oncol; Lee et al, 2019, BMC Cancer; Lee et al, 2021, Support Care Cancer). Brendan noted that particularly HIIT exercise “may prevent unfavorable changes in body composition” compared to a sedentary condition.

The take-home message here remains the same as it’s been in my other posts. If you don’t currently exercise, start now. And then don’t stop. It’s easy to keep laboratory rats active and fit, but humans find many reasons not to challenge themselves with physical activity. If you needed a reason, these studies provide a little encouragement to find your favorite movement modality and make exercise a life-long habit.

REFERENCES

Battaglini CL, Mills RC, Phillips BL, Lee JT, Story CE, Nascimento MG, Hackney AC (2014) Twenty-five years of research on the effects of exercise training in breast cancer survivors: A systematic review of the literature. World J Clin Oncol, 5, 177-190. https://doi.org/10.5306/wjco.v5.i2.177.

Lee K, Kang I, Mack WJ, Mortimer J, Sattler F, Salem G, Dieli-Conwright CM (2019) Feasibility of high intensity interval training in patients with breast Cancer undergoing anthracycline chemotherapy: a randomized pilot trial. BMC Cancer, 19, 653. https://doi.org/10.1186/s12885-019-5887-7.

Lee K, Norris MK, Wang E, Dieli-Conwright CM (2021) Effect of high-intensity interval training on patient-reported outcomes and physical function in women with breast cancer receiving anthracycline-based chemotherapy. Support Care Cancer, 29, 6863-6870. https://doi.org/10.1007/s00520-021-06294-7.

Parry TL, Hayward R (2015) Exercise training does not affect anthracycline antitumor efficacy while attenuating cardiac dysfunction. Am J Physiol Regul Integr Comp Physiol, 309, R675-83. https://doi.org/10.1152/ajpregu.00185.2015.

Smuder AJ, Nguyen BL (May 18, 2023) Cardiorespiratory muscle response to chemotherapy and exercise. ACSM’s From Around The Field webinar.

Can Meditation Fight Cancer?

While it seems like a pretty fantastical concept, a group at the University of California San Diego just received a five-year, $10M grant to examine just that.

Specifically, the InnerScience Research Fund will support ongoing research at UC San Diego’s School of Medicine to determine the biological effects of meditation. Researchers led by Dr. Hemal H. Patel (Dept. of Anesthesiology) are exploring whether meditation can modulate the progression of serious illnesses.

From the UC San Diego Today press release (May 16, 2023):

Researchers are gathering a variety of information from a large group of participants.

“As part of a continuing study entitled “QUest to ANalyze a Thousand hUmans Meditating,” or QUANTUM, Patel and his team are assessing the impact of meditation on nearly 2,000 individuals undergoing intensive meditative experiences. The goal is to capture a depth of unbiased information from a large cohort of healthy and non-healthy individuals to gain insights into the impact of meditation.”

Study participants are contributing a plethora of biometric data obtained via wearable technology, “including heart rate, heart rate variability, sleep, activity and more. That data is then coupled with health survey results and “omic” studies being conducted on blood, microbiome, urine and tears.” Brain activity has also been measured and analyzed.

Perhaps the most unexpected statement in the entire press release was the following: “Early analysis is showing promising results from meditation in impeding serious illnesses such as cancer.”

This is quite an announcement coming from a highly-respected research institution, so I am particulary intrigued.

It would be wonderful to find that the benefits of meditation go far beyond improving one’s sense of calm — lotus position optional!

On the one hand, it’s not difficult to believe that harnessing the mind through meditation could have a dramatically positive impact on one’s health. As I reported in an older post, researchers have elucidated the biochemical pathway by which stress can lead to cancer recurrence in breast cancer survivors. So if we’re able to do the opposite–inviting in a sense of peace and keeping stress at bay–it stands to reason that we affect disease progression. After all, we’ve known for a long time about the benefits of meditation on one’s mental well-being, why not one’s physical health too?

On the other hand, it’s important to understand that meditation alone should not be considered a treatment or cure for cancer. But as my last post on complementary medicine pointed out, cancer patients are increasingly turning to practices such as meditation to help them navigate the cancer experience as they undergo conventional treatment. The added benefits of helping halt the proliferation of a tumor would make meditation an important adjuvant therapy.

This is one story that I will be keeping a close eye on!

“Not Going It Alone”: Complementary Cancer Therapies

With as much sophisticated research as has been done on cancer, it still remains a confounding disease and much of the treatment may seem to be, for lack of a better word, medieval.

So it shouldn’t seem surprising that cancer patients also reach out for less conventional therapy to help themselves through the treatment process.

First, a clarification of terms used in this post:

Acupuncture is utilized as a non-standard treatment (for those who can take more poking)
  • Conventional medicine: chemotherapy, radiation, surgery, immunotherapy, etc., prescribed by your medical team.
  • Complementary medicine: non-standard treatment used in conjunction with conventional treatment; also called Integrative Medicine.
  • Alternative medicine: non-standard treatment used instead of conventional treatment.

Therefore, generally speaking, what distinguishes complementary from alternative medicine is whether it’s used with standard medical treatment.

According to a study (Crudup et al., 2021) that was presented at the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), 73% of breast cancer patient participants stated that they employed complementary therapies in their treatment. However, while oncologists were supportive of such therapies, they were not aware of the extent to which their patients utilized them and thought that only 43% of their patients did.

Patients get more benefit from spiritual practices than most oncologists realize

Furthermore, oncologists felt that counseling, support groups, exercise, etc. were the most effective non-standard therapies, in contrast to patients who found great benefit in meditation, mindfulness and spiritual practices. While two-thirds of both patients and oncologists felt that complementary medicine improved quality of life, a majority of patients also felt that it improved their outcomes.

Wayne Jonas, MD, a co-author of this study, says: “Cancer is a complex disease that affects every component of a patient’s life. While conventional medicine is effective for curing disease, it can fall short in helping patients heal. Patients are turning to these therapies to look for hope and to improve their quality of life and well-being after diagnosis… .”

What types of therapies do these include? The website “Cancer Health” provides examples of some complementary treatments (see here for an explanation of each):

Acupuncture
Aromatherapy
Art Therapy
Biofeedback
Cannabis
Herbal Therapies
Labyrinth Walking
Massage
Meditation
Music/Dance Therapy
Qigong
Spirituality
Tai Chi
Traditional Medicine (Ayurvedic, Chinese, etc.)
Vitamins and Supplements
Yoga

[This list is by no means exhaustive.]

I used a number of these complementary therapies myself and can attest to the important role they played in my recovery. As Dr. Jonas points out above, conventional treatments “can fall short in helping patients heal” [emphasis mine], whereas non-standard therapies seem to focus on that aspect.

I believe that these additional therapies, particularly more spiritual ones, are what give us hope throughout the cancer experience. Patients should be encouraged to seek out additional, complementary therapies to help themselves move through treatment, fully supported by their oncologists and ideally also guided by them.

Did you rely on complementary or alternative treatments to help you through your cancer journey?

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REFERENCES

Original Research

Abstract for presentation:

Crudup et al. (2021) Awareness, perceptions, and usage of whole person integrative oncology practices: Similarities and differences between breast cancer patients and oncologists. Presented at 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), https://meetings.asco.org/abstracts-presentations/200685

Published research article:

Crudup et al. (2021) Breast cancer survivorship and level of institutional involvement utilizing integrative oncology. J Clin Oncol,  39, no. 15_suppl. e18588,
https://www.doi.org/10.1200/JCO.2021.39.15_suppl.e18588

Synopses

The ASCO Post Staff (June 7, 2021; updated June 15, 2021) Use of integrative medicine by patients with breast cancer. ASCO Post, https://ascopost.com/news/june-2021/use-of-integrative-medicine-by-patients-with-breast-cancer/

Tien C (June 28, 2021) Oncologists Underestimate the Number of Breast Cancer Patients Who Use Complementary Medicine. Cancer Health, https://www.cancerhealth.com/article/oncologists-underestimate-number-breast-cancer-patients-use-complementary-medicine

Descriptions of complementary therapies

Living with Cancer: Complementary Therapies. Cancer Health, https://www.cancerhealth.com/basics/health-basics/complementary-therapies

Mindfulness 101: Noticing the Qualities

The main reason why I started a meditation practice was because I had been diagnosed with breast cancer and was, to put it mildly, freaking out.

As a naturally anxious person, the diagnosis blew the roof off my ability to cope and plunged me into a nightmarish situation. Anyone who’s ever dealt with severe anxiety will tell you that nothing is more important than making it stop.

Over the years, my anxiety gathered enough power that it was able to blindside me. Cancer anxiety practically wrecked me.

When my radiation oncologist recommended mindfulness meditation, I felt empowered by the thought of gaining control of my runaway anxiety without the need for medication.

I was hoping meditation would enable me to sit in peace in the midst of chaos. But I imagined that as feeling no stress, as in, being numb to anxiety-provoking stimuli.

That simply doesn’t exist. I wanted to not experience any stressful situations, but there is always stress. We can’t change that. Mindfulness meditation was only going to help me change the way I reacted to it.

So here I am, more than six years after initally starting a daily meditation practice and guess what? I still have stress, I still feel anxiety.

However, what did change is that I can define it now. When I become aware of agitation and anxiety, I know to pause and bring attention to how it manifests in my body.

What does it feel like? Tightness, heat, rapid breath?

Where does it show up? Face, temples, chest, stomach?

Is there a color or sound or smell associated with it? Does it have a “texture”?

Does anxiety have an odor? Next time stop and take a whiff.

I can relax my muscles, sink into the earth, breathe deeply and notice the qualities of anxiety. By pulling apart what is happening, I slow time down. Instead of being hit by a locomotive full force, I walk around the train cars. I can notice how I feel as I pass through the experience.

Is it pleasant? No. Does it always work immediately? No. However, I can see it coming, and as a result, I relax into it. It is the awareness of the anxiety that helps me through it, not a numbness to it. This leads me to acceptance of the situation instead of bracing against it.

On one level, it’s a little discouraging to still be dealing with the unsettling nature of stressors. But I am heartened by the empowerment that mindfulness offers. I have evolved enough that I know I don’t have to go back to being thrashed by the whirlwind. I can sit inside it and watch it swirl and pass through. Every time I do this, it gives me more confidence for the next time.

Is this something that might help you too?

Things I Wish I’d Known About Breast Cancer, Part 2

This post continues what I started in the last post…a few things about breast cancer that I wasn’t aware of at the time of my diagnosis. Knowing the following would have made things a little less stressful:

1. Lumpectomy is a relatively uncomplicated surgery. I wish someone had explained this to me because I was a total wreck going into surgery (which happened to be the only surgery that I had ever had up to that point, making everything 10 times worse). Although I had decided against a full mastectomy, I was still so afraid of what a lumpectomy would entail, what I’d look like and how long it would take me to recover from losing a chunk of flesh.

The reality was…I was back at work the next week. No drainage tubes, no need for heavy analgesics — just a couple of ibuprofin the night after surgery because skipping coffee that morning resulted in a headache, but that was it. It was even hard to tell that I’d had my lump excised. Wish I could go back to my earlier self and tell her not to worry.

Stethoscopes are emotionless. Oncologists can seem to be too, but that’s by design.

2. Doctors are not in a hurry to give you good news. I think there’s a general feeling among medical professionals that there’s so much that can go poorly during cancer treatment that your doc isn’t going to go out of their way to pump you full of optimism. They probably practice keeping an emotionless face as they deliver all sorts of news, both good and bad. As a patient, however, I watched every flicker on my oncologist’s face for an indication of how things were “really” going. I feared that there was something he wasn’t telling me.

It wasn’t until perhaps a year or so later when I was expressing my fears to him about possible abnormalities inside my body that he uttered the phrase, “but you have your health”…and I was taken aback because I had never heard him sound so positive. It was almost a shock to hear him confirm that I was actually considered healthy.

3. Don’t expect things to be the same as before. Accepting that part of your life has changed will make it much easier to go on. This took me a while to appreciate because I was expecting to get back to doing and feeling everything the same as before my diagnosis.

But chemo (and eventually, age) pushed me through menopause, and I had to come to grips with, say, a high-intensity interval workout requiring more recovery time and that I had trouble remembering people’s names. Once I got to that point of acceptance, life after cancer treatment became easier, although it did take a number of years to get there.

4. Hair takes a while to grow back in. The reason I created posts with photographs that illustrated the cancer journey that my hair went through (here and here) was because I could not find good photos on the internet documenting the process. I did see images of a woman a few weeks after stopping chemo with little stubs already visible, but that was not my experience and it made my anxiety over my slow regrowth even worse.

Walking around with no hair was getting old and I was getting more desperate by the day to see evidence of sprouts!

If you’ve ever googled your chemo drug name + “hair loss”, you understand the fear: the first search result is usually a law office gathering info on behalf of cancer patients whose hair never grew back!

It took a number of months before my folicles woke up and actually started growing. I remember the moment that I finally saw growth on the front of my head and it was as if the heavens had opened up and divine light poured out onto me. Seriously. I would have avoided a lot of stress if someone had just told me that it’s gonna be a while.

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Ok, ok, to be fair, my oncologist did urge patience with the regrowth but I was a jumbled mess of nerves and was feeling overwhelmed. All the internet propaganda about both (1) other women having much faster regrowth, or (2) other women never getting their hair back terrified me. Note to self: when feeling desperate, stay off the internet!