Fisetin to Improve Physical Function in Stage I-III Breast Cancer Survivors

PRIMARY OBJECTIVE: I. To determine the effect of fisetin on physical function, as assessed using the 6-minute walk distance (6MWD), in frail older breast cancer survivors. SECONDARY OBJECTIVES: I. To determine the effect of fisetin on other measures of physical function (grip strength, short physical performance battery \[SPPB\], frailty phenotype, physical function component of the 36 item short form survey \[SF-36\]). II. To determine the effect of fisetin on fatigability (Borg Rating of Perceived Exertion \[RPE\]). III. To determine the effect of fisetin on neuropathy (Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 \[QLQ-CIPN20\]). IV. To determine the effect of fisetin on cognitive function (Patient Reported Outcomes Measurement Information System \[PROMIS\] cognitive function short form). V. To determine the effect of fisetin on health-related quality of life (SF-36). VI. To determine the effect of fisetin on sleep (Insomnia Severity Index \[ISI\]). VII. To determine the effect of fisetin on anxiety (GAD-7). VIII. To determine the effect of fisetin on depression (PHQ-8). IX. To determine the effect of fisetin on local and distant recurrence free survival. X. To determine the effect of fisetin on breast cancer specific survival and overall survival. XI. To evaluate the safety and tolerability of fisetin (physician and patient-reported Common Terminology Criteria for Adverse Events \[CTCAEs\]). XII. To estimate rates of adherence to fisetin (pill diary). EXPLORATORY OBJECTIVES: I. To determine the effect of fisetin on p16 expression in peripheral CD3+ T-cells. II. To determine the effect of fisetin on circulating senescence-associated secretory phenotype (SASP) inflammatory factors. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive fisetin orally (PO) on days 1, 2, and 3. Treatment repeats every 2 weeks for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples throughout the trial. ARM B: Patients receive placebo PO on the trial. on days 1, 2, and 3. Treatment repeats every 2 weeks for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples throughout the trial. After completion of study treatment, patients are followed up yearly for up to 3 years.