Hanging on to Fitness and a Few Strands of Hair Through Breast Cancer Treatment

I am a Medical Oncologist, a wife, a mother of 4, runner of 12 marathons training to run my 13th with a goal to qualify for Boston when the diagnosis of breast cancer caused a significant detour in my well-planned life. When I asked for guidance on how to continue to stay fit while receiving treatment, I received blank stares and found little data. While I never intended to be in this experiment, I find myself now generating my own data about fitness through the diagnosis and treatment of breast cancer. I am writing this in hopes to help others who find themselves in this same situation.


Wisdom Wednesday: Could Exercise be the Next Hot Immuno-oncology Drug?

The immune system is an amazing and complicated thing. It is well beyond the scope of this blog post to explain the details of this remarkable system. But to grossly simplify, it’s job is to recognize the things that don’t belong in our body and get rid of them while at the same time be leaving the parts of us that should be there, alone. This actually works amazingly well for most of us most of the time, but when it is less than perfect, we get sick. We may get infections or cancer when it fails to get rid of bacteria, viruses or cancer cells and we may get autoimmune diseases when it attacks our normal body parts. Although every day our immune system is effectively ridding our body of defective cells that have turned into cancer cells, these cancer cells are also working hard to survive and when they figure how to hide from the immune system, this is when things get bad. The cancer cells can grow and divide, and may develop the potential to become invasive which means they can grow through surrounding normal tissues and spread to other parts of the body through the blood and lymphatic system. In the past decade, some of the most promising new therapies for cancer have been designed to enhance the immune system such that it can find and attack the cancer more effectively.

Although there is still a lot of work to do to fully understand this, there is interesting data on how exercise may enhance the immune system. This is important for anyone, but may be critically important for people with cancer. Is it possible that exercise may result in changes in the immune system that may enhance the effectiveness of chemotherapy and radiation? We don’t have the answer to this question yet, but I read a great review article that nicely summarizes what we know.(1) Much of this data involves rats rather than humans, but I think that there are a lot of interesting clues that should lead to important human clinical trials. This paper focused on the following topics:

Chronic inflammation and malignant cellular transformation

Immune surveillance

Immune escape and tumor progression

Triggering an immunogenic response to the tumor

This is a really interesting paper that I highly recommend reading. But I will summarize the key information here.

The Role of Chronic Inflammation in Cancer

Chronic inflammatory states which can include chronic infections, autoimmune disease, and obesity, can lead to the conditions in the body which result in malignant transformation of cells. In other words, normal cells become cancer cells. There have been numerous studies in healthy humans that have shown that exercise results in reduced inflammation through a number of different mechanisms. Only a few small clinical trials in cancer patients have been done to try to understand how exercise may impact blood markers of inflammation, and early results seem promising. In general, these studies have shown reductions in markers of inflammation that can be checked with blood tests. Although these studies are very intriguing, they are all very small, with different types of patients receiving different types of chemotherapy and therefore no definitive conclusions or recommendations can be made based on these studies with regard to exercise’s ability to minimize a proinflammatory process as a means to slow or inhibit cancer cell growth.

Immune Surveillance

I mentioned that one of the big important jobs of the immune system is to be on the lookout for cancer cells and get rid of them before they have a chance to cause any trouble. This is known as immune surveillance. The cells that do this are called Natural Killer Cells. Cool name, huh? Anyway, these guys are important because they recognize cancer cells and eliminate them. At the same time though, as I mentioned earlier, cancer cells are busy trying to hide from these cells and those that have figured out how to hide may continue to grow. And these sneaky little devils may not only hide from these NK cells, they may figure out how to suppress the immune system in general. We know all of this because of years of research on both animals and humans.

So what do we know about the relationship between exercise and NK cells? In studies that have included healthy humans, there have been mixed results. In one study, they assigned the study subjects to complete an exercise program for 10 weeks.(2) Then they evaluated NK cell-mediated cytotoxicity (NKCC). In other words, how well did the NK cells from these people kill cancer cells in a petri dish after they participated in a 10-week exercise program. This study found that NKCC was increased in these people. However, other similar studies in humans have not found a difference in NKCC after an exercise program.(3, 4)

A few studies have looked at NK cells in cancer patients who have been randomized to participate in an exercise program or no exercise. One study found increased NKCC in a group of breast cancer patients randomized to exercise compared to the non-exercising group.(5) However, another similar study but including overweight breast cancer patients and adding low-calorie diet, did not find a difference in NKCC between exercising and the non-exercising group.(6)

Immune escape and tumor progression

In other words, this is what happens with the cancer cells have figured out how to hide from the immune system and by doing this, they are begging to thrive and cause trouble. This is an area where a lot more research needs to be done to see how exercise may impact this process. There have been some interesting animal studies that may give us some clues. There was a study in mice that had tumors implanted in their skin where they compared what happened to these tumors for mice that were allowed to run on a wheel vs no activity.(7) The mice that had access to exercise had slower growth of their tumors compared to the sedentary mice.

Triggering an immunogenic response to the tumor

Another important cell that is part of the immune system is the T-cell. T-cells are stimulated to grow and divide when they see an antigen on a cell that should be eliminated. If you look for T-cells in a cancer that has been removed from a patient, it is not uncommon that these are not found or are in small numbers, and this is not a good sign for the patient with that cancer. Dendritic cells (DC) are another cell in the immune system. These cells are important in starting an immune response to a cancer cell.

It is not known how exercise in humans impacts DC function, but again, there are some interesting animal studies. A study in rats found that after 5 weeks of exercise, the DC function for these rats was improved8.

In summary, there is still a lot of work to be done to better understand how exercise impacts the immune system in ways that may prevent cancer in the first place, but also how it may slow cancer growth and potentially help cancer therapies work better.

1. Koelwyn, GJ. et. al. Exercise in Regulation of Inflammation-immune Axis Function in Cancer Initiation and Progression. Oncology. 2015 December; 29 (12).

2. Woods JA, Ceddia MA, Wolters BW, et al. Effects of 6 months of moderate aerobic exercise training on immune function in the elderly. Mech Ageing Dev. 1999; 109:1–19. [PubMed: 10405985]

3. Fahlman M, Boardley D, Flynn MG, et al. Effects of endurance training on selected parameters of immune function in elderly women. Gerontology. 2000; 46:97–104. [PubMed: 10671807]

4. Campbell PT, Wener MH, Sorensen B, et al. Effect of exercise on in vitro immune function: a 12- month randomized, controlled trial among postmenopausal women. J Appl Physiol (1985). 2008; 104:1648–1655. [PubMed: 18403448]

5. Fairey AS, Courneya KS, Field CJ, et al. Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors. J Appl Physiol (1985). 2005; 98:1534–1540. [PubMed: 15772062]

6. Saxton JM, Scott EJ, Daley AJ, et al. Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial. Breast Cancer Res. 2014; 16:R39. [PubMed: 24731917]

7. Betof AS, Lascola CD, Weitzel D, et al. Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise. J Natl Cancer Inst. 2015; 107:djv040. [PubMed: 25780062]

8. Chiang LM, Chen YJ, Chiang J, et al. Modulation of dendritic cells by endurance training. Int J Sports Med. 2007; 28:798–803. [PubMed: 17436203]

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