Reishi Mushroom Extract for Fatigue and/or Arthralgias/Myalgias in Patients With Breast Cancer on Aromatase Inhibitors

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.

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
• Patients who have had a recent surgery or procedure should be healed and cleared by their clinician and/or surgeon per local standards, prior to registration

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-examples-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)
• Planned surgery or procedure during time on study and ≤ 14 days after last dose, due to bleeding risks