Exercise Intervention for Breast Cancer-Related Inflammation

(DECODE Trial)

Recruiting at 1 trial location

Overseen By Melinda Stolley, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must be taking: Anthracyclines, Anti-Her2

Disqualifiers: Cardiovascular disease, Metastatic, Weight loss, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 16-20 weeks

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators or your doctor for guidance.

What data supports the effectiveness of the treatment Taking Charge during Treatment (TCT) Intervention, Lynparza for breast cancer-related inflammation?

Research shows that exercise can reduce inflammation and fatigue in breast cancer patients, which are key components of the TCT Intervention. High-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been found to improve inflammatory markers and physical fitness in breast cancer survivors, suggesting that exercise is beneficial in managing inflammation. ^{1 2 3 4 5}

Is exercise intervention safe for breast cancer patients?

Research shows that exercise interventions are generally safe for breast cancer patients, even during chemotherapy. Studies have found that supervised exercise can help manage inflammation and reduce fatigue without significant safety concerns. ^{1 6 7 8 9}

How does exercise intervention differ from other treatments for breast cancer-related inflammation?

Exercise intervention is unique because it naturally reduces inflammation by improving the levels of certain proteins in the body, like IL6 and TNFα, which are linked to inflammation. Unlike traditional drug treatments, exercise also enhances physical fitness and body composition, offering a holistic approach to managing breast cancer-related inflammation. ^{2 3 5 10 11}

What is the purpose of this trial?

Very little is understood about the off-target vascular mechanisms of anti-cancer drug toxicity and the impact of exercise on these changes. Much of what has been learned about molecular pathways regulating vascular endothelial function has been established by logical expansion of knowledge obtained through experimental studies (e.g., discovery of endothelium-derived relaxing factor/nitric oxide). Within the last 10 years technological advancements of -omics approaches, such as RNA-sequencing and shotgun proteomics, have dramatically reduced the cost and technical challenge of accessing these tools for discovery-based research. Investigators are now able to obtain unbiased datasets showing changes in transcript or protein expression within complex samples. With cost and accessibility of sequencing is no longer being substantial bottleneck, one of major challenges researchers now face is determining how to meaningfully interpret profiles from large datasets. The extensive characterization of molecular pathways impacting inflammatory responses, endothelial function and angiogenesis, the pathway and network analysis tools will be an asset for identification molecular pathways relevant to alterations in microvascular endothelial function. The investigators preliminary studies on only a small number of samples highlights this potential of the proposed approach to lead to identify personalized medicine-based profiles that will predict patients are likely to develop microvascular endothelial dysfunction from CTx.

Eligibility Criteria

This trial is for adults assigned female at birth, diagnosed with non-metastatic breast cancer, receiving certain chemotherapy including anthracyclines or anti-Her2 therapy. Participants must be able to exercise safely and identify as Black/African American or non-Hispanic White. Excluded are those who don't speak English, have metastatic disease, are pregnant/lactating, have cardiovascular disease, prior similar treatments or significant recent weight loss.

Inclusion Criteria

Self-identifies as Black/African American or non-Hispanic White

Willing to complete all study activities

I am undergoing treatment for breast cancer that includes specific chemotherapy drugs or targeted therapy.

Exclusion Criteria

I have heart disease with symptoms or an ejection fraction below 50%.

Non-English speaking

I have had chemotherapy or targeted head and neck cancer treatment before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 16-20 week intervention promoting exercise during cancer treatment, including regular physical activity and resistance training.

16-20 weeks

2-4 visits (in-person), weekly text messages

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 12-15 months.

12-15 months

3 visits (in-person)

Treatment Details

Interventions

• Taking Charge during Treatment (TCT) Intervention

Trial Overview The study tests the 'Taking Charge during Treatment' (TCT) Intervention aimed at understanding how cancer treatment-induced inflammation affects blood vessel function and if exercise can mitigate these effects. It uses advanced -omics technologies to predict microvascular dysfunction from chemotherapy.

Participant Groups

Group I: Taking Charge during Treatment (TCT) Intervention Active Control 1 Intervention

Taking Charge during Treatment (TCT) Intervention. TCT is a 16-20week intervention that promotes adoption of the ACSM exercise guidelines for cancer survivors during treatment, including regular moderate to vigorous physical activity (150 minutes per week of moderate activity or 75 minutes per week of vigorous activity) and a minimum of twice weekly resistance training (RT) minutes during CTx and after. Participants will receive "Take Charge" program binder, 2-4 x weekly text messaging, activity tracker and resistance bands.

Group II: Control Group Active Control 1 Intervention

To ensure scientific rigor allowing us to test causal pathways associated with exercise, women will be randomized to the TCT intervention or control group arm. The control group will not receive the TCT intervention The investigators experience teaches us that to increase the likelihood of retaining control group participants, the investigators must offer some resources. Thus, the investigators will provide the control group with a one-page summary of the American College of Sports Medicine exercise recommendations, and the "Take Charge" program binder at the completion of the study. Participants will also receive resistance bands and activity tracker at the end of the study. 95 The investigators will also send weekly text messages with supportive content not related to exercise or lifestyle (i.e., a riddle, "take a moment to smile today," a picture of a baby animal).

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

Findings from Research

A 16-week exercise intervention involving resistance and high-intensity interval training (RT-HIIT) significantly reduced inflammation markers (IL-6 and CD8a) in breast cancer patients undergoing chemotherapy, which correlated with lower levels of fatigue.

The study found that changes in these inflammation markers mediated the exercise's beneficial effects on fatigue, suggesting that exercise can be an effective strategy to combat chemotherapy-induced fatigue by reducing inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammation Mediates Exercise Effects on Fatigue in Patients with Breast Cancer. Hiensch, AE., Mijwel, S., Bargiela, D., et al.[2023]

A 12-week study involving 40 breast cancer survivors showed that high-intensity interval training (HIIT) led to greater reductions in body mass, fat mass, and inflammatory markers (like TNF-α and IL-6) compared to moderate-intensity continuous training (MICT).

HIIT also significantly improved physical fitness, as indicated by increases in VO2peak and lower body strength, suggesting it may be a more effective exercise therapy for managing chronic inflammation and improving health outcomes in breast cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Inflammatory Markers, Body Composition, and Physical Fitness in Overweight/Obese Survivors of Breast Cancer: A Randomized Controlled Clinical Trial. Hooshmand Moghadam, B., Golestani, F., Bagheri, R., et al.[2021]

In a study involving 11 breast cancer survivors, 16 weeks of combined aerobic and resistance exercise training significantly reduced the production of pro-inflammatory cytokines IL-1ß and IL-6 in monocytes, suggesting an anti-inflammatory effect of exercise.

Acute exercise led to a temporary decrease in the expression of toll-like receptors (TLR2 and TLR4) on monocytes, indicating a potential immediate response to exercise, although this effect was not sustained with ongoing training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise-induced modulation of monocytes in breast cancer survivors. Khosravi, N., Hanson, ED., Farajivafa, V., et al.[2022]

In a study involving 394 cancer patients, both high-intensity (HI) and low-to-moderate intensity (LMI) exercise did not show significant differences in inflammatory markers, indicating that exercise intensity may not impact inflammation levels during cancer treatment.

However, in a subgroup of 154 breast cancer patients undergoing chemotherapy, HI exercise led to a smaller increase in C-reactive protein (CRP) and tumor-necrosis factor alpha (TNFA) immediately after treatment compared to LMI, suggesting that HI exercise may help mitigate chemotherapy-related inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise intensity and markers of inflammation during and after (neo-) adjuvant cancer treatment. Schauer, T., Mazzoni, AS., Henriksson, A., et al.[2022]

A meta-analysis of eight high-quality trials involving 478 breast cancer survivors found that exercise significantly reduced inflammatory markers such as IL6, TNFα, and IL8, suggesting a positive effect on the tumor microenvironment.

The results support the idea that exercise can help modulate chronic low-grade inflammation in breast cancer survivors, reinforcing the importance of exercise as part of their treatment and recovery plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Exercise Training on Mediators of Inflammation in Breast Cancer Survivors: A Systematic Review with Meta-analysis. Meneses-Echávez, JF., Correa-Bautista, JE., González-Jiménez, E., et al.[2018]

In a study of 75 postmenopausal breast cancer survivors, exercise did not significantly change levels of inflammatory markers IL-6, CRP, and TNF-α compared to usual care, suggesting that the relationship between physical activity and breast cancer survival may not be directly linked to inflammation.

However, women who achieved 80% of their exercise goals showed a significant reduction in IL-6 levels, indicating that meeting exercise targets may have beneficial effects on inflammation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on markers of inflammation in breast cancer survivors: the Yale exercise and survivorship study. Jones, SB., Thomas, GA., Hesselsweet, SD., et al.[2022]

In a pilot trial involving 10 breast cancer patients undergoing neoadjuvant chemotherapy, adding a supervised exercise program resulted in a significant decrease in body mass index (BMI) compared to those receiving chemotherapy alone (28.0 vs. 35.8, P = 0.03).

While the exercise group showed a trend towards lower Ki-67 levels (7% vs. 29%, P = 0.14), indicating potential benefits in tumor proliferation rates, the difference was not statistically significant, suggesting further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bootcamp during neoadjuvant chemotherapy for breast cancer: a randomized pilot trial. Rao, R., Cruz, V., Peng, Y., et al.[2021]

In a 12-week supervised exercise program involving 141 overweight or obese breast cancer patients, adherence to national physical activity guidelines increased significantly from 38.3% at baseline to 44.7% after 26 weeks, indicating that exercise can help maintain physical activity during adjuvant endocrine therapy.

The study also found significant improvements in metabolic syndrome, body composition, health-related quality of life, and breast cancer-specific symptoms, suggesting that supervised exercise not only enhances physical activity but also contributes to overall health and well-being in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of supervised exercise during adjuvant endocrine therapy in overweight or obese patients with breast cancer: The I-MOVE study. Ormel, HL., Schröder, CP., van der Schoot, GGF., et al.[2021]

A supervised exercise training program (SETP) was safe for women undergoing anthracycline chemotherapy for breast cancer and significantly improved their cardiorespiratory fitness, as indicated by increased estimated peak VO2.

However, the exercise program did not show significant effects on cardiac toxicity markers, such as left ventricular ejection fraction (LVEF), compared to usual care alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on cardiac toxicity markers in women with breast cancer undergoing chemotherapy with anthracyclines: a randomized controlled trial. Antunes, P., Joaquim, A., Sampaio, F., et al.[2023]

An 8-week combined aerobic and strength exercise program for 16 female breast cancer survivors did not significantly alter the levels of key cytokines related to breast cancer, such as IL6 and IL8, indicating limited impact on inflammation or immune response.

However, the exercise intervention did stabilize CTACK levels in the exercise group, while levels increased in the control group, suggesting a potential benefit of exercise in maintaining certain cytokine levels post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training and cytokines in breast cancer survivors. Gómez, AM., Martínez, C., Fiuza-Luces, C., et al.[2011]

Exercise may improve inflammatory marker levels in breast cancer survivors, potentially leading to better health outcomes.

This narrative review highlights the need for further research to clarify the relationship between exercise and inflammation, as well as the biological mechanisms involved, given the inconsistencies found in existing literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breast Cancer Survivors, Common Markers of Inflammation, and Exercise: A Narrative Review. Mills, RC.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Inflammation Mediates Exercise Effects on Fatigue in Patients with Breast Cancer. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of High-Intensity Interval Training vs. Moderate-Intensity Continuous Training on Inflammatory Markers, Body Composition, and Physical Fitness in Overweight/Obese Survivors of Breast Cancer: A Randomized Controlled Clinical Trial. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Exercise-induced modulation of monocytes in breast cancer survivors. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Exercise intensity and markers of inflammation during and after (neo-) adjuvant cancer treatment. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The Effect of Exercise Training on Mediators of Inflammation in Breast Cancer Survivors: A Systematic Review with Meta-analysis. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Effect of exercise on markers of inflammation in breast cancer survivors: the Yale exercise and survivorship study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Bootcamp during neoadjuvant chemotherapy for breast cancer: a randomized pilot trial. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of supervised exercise during adjuvant endocrine therapy in overweight or obese patients with breast cancer: The I-MOVE study. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Effects of exercise training on cardiac toxicity markers in women with breast cancer undergoing chemotherapy with anthracyclines: a randomized controlled trial. [2023]

10. Germany pubmed.ncbi.nlm.nih.gov

Exercise training and cytokines in breast cancer survivors. [2011]

11. United States pubmed.ncbi.nlm.nih.gov

Breast Cancer Survivors, Common Markers of Inflammation, and Exercise: A Narrative Review. [2020]