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About 20%-70% of breast cancer survivors experience fatigue after cancer therapy. Because epidemiologic evidence shows that old age is a risk factor for fatigue in adults with cancer history, older breast cancer survivors suffer from even more fatigue than younger survivors. The purpose of this study is to test types of walking exercise interventions and their ability to reduce fatigue in older breast cancer survivors.

Women with breast cancer often experience severe fatigue (asthenia) after cancer therapy, seen in approximately 40% of breast cancer survivors. Because older age is a risk factor for fatigue, older breast cancer survivors are at an increased risk versus those in younger age groups. Prior evidence suggests that aerobic exercise reduces inflammation and bioenergenesis disturbance, which are key factors that drive the pathogenesis of fatigue. Although interventional studies suggest that aerobic exercise can improve fatigue in younger breast cancer survivors, anti-fatigue effects of aerobic exercise tended to decrease with increasing age. The investigators postulate that novel interventions combined with aerobic exercise can enhance its effectiveness and alleviate severe fatigue further in older breast cancer survivors.

In this pilot randomized clinical trial, the investigators will enroll 24 female cancer survivors aged � 60 years who were diagnosed with invasive breast cancer but have completed adjuvant therapy for at least 3 months but no more than 1 year. Participants will be randomly assigned to either a center-based walking exercise intervention or a home-based walking exercise intervention for an 8 week period. By completing this pilot study, the investigators will be able to collect preliminary data; refine the recruitment, measurement, randomization, and retention strategy; and adjust the statistical strategy and timeline for the potential full-scale randomized clinical trial.

Inclusion Criteria:

• Consent to participate in the study

• Age â‰� 60 years old

• Had stage I-III invasive breast cancer

• The cancer is diagnosed in 2021 or 2022

• Completed adjuvant therapy for at least 3 months but no more than 1 year

• Willingness to participate in all study procedures

• Had at least moderate-level fatigue (defined as raw score â‰� 8 on the PROMIS Measure)

Exclusion Criteria:

• Failure to provide informed consent

• Current involvement in rehabilitation program

• Absolute contraindications to exercise training

• Significant cognitive impairment

• Progressive, degenerative neurologic disease

• Hip fracture, hip or knee replacement, or spinal surgery within past 4 months

• Other significant comorbidities that may impair ability to participate in the exercise intervention

• Pregnant

• Regular consumption of nicotinamide riboside supplement

• Simultaneous participation in other interventional studies

• Had no or very mild fatigue (defined as raw score â‰�7 in PROMIS)

• Diagnosis of any of the following medical conditions in past three years (coronary heart disease, angina, heart attack, heart failure, stroke, high blood pressure, chronic obstructive pulmonary disease, chronic bronchitis, arthritis, diabetes mellitus, and chronic kidney disease), as measured by Behavioral Risk Factor Surveillance System

• Receipt of any oral or intravenous antibiotic 4 weeks prior to screening

• Receipt of any probiotics within 4 weeks of screening

• History of active treatment for HIV, hepatitis B, or hepatitis C infection

• Positive stool cultures for enteric pathogens, including Clostridium difficile

• Excessive alcohol use (i.e., > 14 drinks/week) or alcohol abuse (i.e., > 5 drinks/day for males or > 4 drinks/day for females)

• Other substance abuse within the past 3 years

• Smoking history in past 3 years