Clinical Trial Finder

Inclusion Criteria:

• - Age ≥ 18 years.

• - History of breast cancer, estrogen receptor positive (ER+), Her 2 positive or negative.

• - Fatigue ≥ 4/10.

• - Currently post-menopausal (as defined by National Comprehensive Cancer Network (version 4.2024), taking any aromatase inhibitor in the curative setting and planning to be on such for at least 8 weeks after registration.

(Patients on concurrent ovarian suppression [such as with leuprolide acetate, goserelin] are allowed) ; CDK 4/6 inhibitors abemaciclib, ribociclib ARE allowed.

• - Prior treatment: last chemotherapy ≥ 90 days prior to randomization (if treated with chemotherapy) - On a stable dose of pain medications if pain medications are being regularly used.

(i.e., no change in dosage in the past 30 days)

• - If on supplements, must be on stable dose with no plan to change; not on or planning any acupuncture or other specific supportive modalities for fatigue or AI arthralgias.

• - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2.

• - White blood cell count (WBC) ≥ 3,000/mm^3 (obtained ≤ 30 days prior to randomization) - Hemoglobin ≥ 10 g/dL (obtained ≤ 30 days prior to randomization) - Platelet count ≥ 100,000/mm^3 (obtained ≤ 30 days prior to randomization) - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 30 days prior to randomization) - Alanine aminotransferase (ALT) or aspartate transaminase (AST) ≤ 1.2 x ULN (obtained ≤ 30 days prior to randomization) - Prothrombin time (PT)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (obtained ≤ 30 days prior to randomization) - Negative pregnancy test done ≤ 7 days prior to registration, for persons on concurrent ovarian suppression only.

• - Provide informed consent.

• - Ability to complete questionnaires.

• - Willing to return to enrolling institution during the active monitoring phase of the study.

Exclusion Criteria:

• - Other known uncontrolled medical conditions causing fatigue such as untreated thyroid disease, depression, fibromyalgia, chronic fatigue syndrome, infection, autoimmune disease, or active/untreated hepatitis.

• - Allergy to mushrooms.

• - On anticoagulation medication or aspirin or having a known bleeding disorder.

• - On any specific medication for fatigue (e.g., methylphenidate) - Metastatic cancer diagnosis (history of nodal metastases is allowed) - Chronic steroid use, unless on physiologic replacement doses.

• - Current use of any medical mushrooms.

• - On medications for diabetes.

• - History of symptomatic hypotension.

• - Taking CYP3A4, CYP2D6 sensitive substrates which can be located at the following link: https://www.

fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-exampl es-drugs-interact-cyp-enzymes-and-transporter-systems.

• - Drugs which exhibit either >20% inhibition or >20% induction of CYP2E1 in vivo, such as: Acetaminophen, Dapsone, Enflurane, Halothane, Isoflurane, & Theophylline.

• - Taking olaparib.

• - Any of the following because this study involves an agent that has unknown genotoxic, mutagenic and teratogenic effects: - Pregnant persons.

• - Nursing persons.

- Persons on concurrent ovarian suppression who are unwilling to employ adequate contraception (e.g., hormonal methods, barrier methods, intrauterine device, abstinence)

PRIMARY OBJECTIVE:

• I. To evaluate the efficacy of 1,000 mg three times daily (TID) of Reishi mushroom extracts as therapy for cancer-related fatigue measured by uniscale measurement at the end of four weeks.

SECONDARY OBJECTIVES:

• I. To evaluate the efficacy of Reishi mushroom extracts as therapy for cancer-related arthralgias at the end of four weeks and four weeks after cross-over as measured by the Brief Pain index (BPI)-adapted for AI associated arthralgias.

• II. To evaluate the effect of Reishi mushroom extracts on cancer-related quality of life (QOL), as measured by uniscale, at the end of four weeks and four weeks after cross-over.

• III. To evaluate the efficacy of Reishi mushroom extracts on mood, as assessed by the World Health Organization Five Well-Being Index (WHO-5) item well-being scale, at the end of four weeks and four weeks after cross-over.

• IV. To evaluate treatment toxicity between the two treatment arms, as measured by a patient symptom experience diary and weekly calls from the study team.

• V. To evaluate the interest, knowledge, and acceptance of integrative treatments for cancer-related symptoms.

OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive Reishi mushroom extract orally (PO) TID on days 1-28 for weeks 1-4 and then placebo PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO TID on days 1-28 for weeks 1-4 and Reishi mushroom extract PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Arms

Experimental: Arm I (Reishi mushroom extract, placebo)

Patients receive Reishi mushroom extract PO TID on days 1-28 for weeks 1-4 and then placebo PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II (placebo, Reishi mushroom extract)

Patients receive placebo PO TID on days 1-28 for weeks 1-4 and Reishi mushroom extract PO TID on days 1-28 for weeks 5-8 in the absence of disease progression or unacceptable toxicity.

Interventions

Dietary Supplement: - Mushroom Extract

Given Reishi mushroom extract PO

Drug: - Placebo Administration

Given PO

Other: - Quality-of-Life Assessment

Ancillary studies

Other: - Questionnaire Administration

Ancillary studies