Prevention of Frailty With Fisetin and Exercise in Breast Cancer Survivors

Inclusion criteria

• Women who are postmenopausal at the start of study treatment
• Postmenopausal status will be established as follows: Women who are 50 years or older and who are not menstruating for greater than 12 months will be considered postmenopausal. Women who are less than 50 years with an intact uterus and ovaries must have chemically induced menopause (e.g., ovarian suppression) to be considered postmenopausal
• Women with a diagnosis of early-stage breast cancer (stage I, II, III) treated with neo/adjuvant chemotherapy within 12 months of starting study treatment
• No evidence of active/recurrent breast cancer or other serious chronic illnesses
• Have evidence of pre-frail health, defined as a 6-minute walk distance (400-480m) at baseline
• Platelets \> 60,000/mm\^3
• White blood cell count \> 2,000/mm\^3
• Absolute neutrophil count \> 500/mm\^3
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 3.0 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 4.0 x ULN
• Alanine aminotransferase (ALT) ≤ 4.0 x ULN
• Estimated glomerular filtration rate (eGFR) of ≥ 30mL/min/1.73m\^2 per the Modification of Diet in Renal Disease (MDRD) calculation. GFR (mL/min/1.73 m²) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Cancer-directed chemotherapy, biological therapy, or immunotherapy within 30 days prior to the start of study treatment. Exceptions include: trastuzumab, pertuzumab, pembrolizumab, tamoxifen, and aromatase inhibitors
• Surgery and/or radiation within the last 30 days of starting study treatment (Exception: invasive non-major procedures such as an outpatient biopsy)
• Subjects taking medications that are considered prohibited
• Exception: Subjects taking any of the medications under "Temporary medication adjustment required" may participate if they are otherwise eligible AND the medication can be safely withheld (from immediately before the 1st study agent administration until at least 10 hours after the last study agent administration, for each dosing interval)
• On herbal and natural medications with possible senolytic properties (i.e., curcumin, kava kava, St. John's wort) and are unable or unwilling to hold its administration 2 days prior to and during study treatment dosing. Exceptions include cannabidiol (CBD), vitamins, probiotics, and fish oil. Other herbal and natural medications may be permitted or prohibited per clinician discretion
• Subjects taking potentially senolytic agents within the last year: fisetin, quercetin, luteolin, dasatinib or imatinib (or other tyrosine kinase inhibitors), piperlongumine, or navitoclax
• Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc.)
• Issues with tolerating oral medication (such as but not limited to, inability to swallow pills (gastrostomy \[g\]-tubes not allowed), malabsorption issues, ongoing nausea or vomiting during screening, history of Crohn's, gastric bypass/reduction, or celiac disease)
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Currently participating in another intervention research study seeking to improve functional status, alleviate frailty, muscle strength, exhaustion/fatigue, or cognitive function