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Impacts of Medical Marijuana Use on Inflammasome Activation and Breast Cancer Clinical Outcomes: A New Prospective Cohort Study

Jennifer Hu
University of Miami

Co-Authors: Juan Pablo de Rivero Vaccari1, Yan Wang2, Cristiane Takit1, Isildinha M Reis1, Alexandra McMahon1
1University of Miami, 2University of Florida

Background: Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in American women. Some breast cancer patients use Medical Marijuana (MMJ) to manage treatment-related symptoms. Although MMJ is generally considered safe and well-tolerated in cancer patients, there are potential adverse effects and conflicting reports on its interactions with cancer therapies and their impact on clinical outcomes. Therefore, we propose a prospective cohort study of a diverse breast cancer population (50% minorities) to assess the impact of MMJ on clinical outcomes and QOL.

Objective: The objectives are to (i) Assess the impact of MMJ on clinical outcomes and QOL in breast cancer patients after adjusting for age, race/ethnicity, tumor stage, and subtypes; (ii) Evaluate the relationship between inflammasome/inflammatory biomarkers and the biological effects of MMJ on clinical outcomes of breast cancer; (iii) Investigate potential interactions between MMJ properties (i.e., THC/CBD ratio, dose, and type) and cancer treatments on clinical outcomes.

Methods: We proposed to enroll 60 breast cancer patients who plan to initiate MMJ and collect data on patient and tumor characteristics, treatments, clinical outcomes, and adverse reactions to obtain a comprehensive understanding of the usage and effects of MMJ. We will collect subjective and objective data through combined in-person visits and technology-based assessments. In two proof-of-concept pilot studies, we evaluated inflammasome biomarkers in predicting radiotherapy (RT)-related clinical outcomes and the effects of MMJ on chronic pain.

Results: In the first pilot study of 63 breast cancer patients, we showed that RT-induced skin toxicity is significantly higher in patients with higher mean levels of inflammasome markers including caspase-1 (p=0.023), IL-18 (p=0.04), and hsCRP (p=0.028). Patients with post-RT pain 4+ have higher mean levels of ASC (p=0.017), IL-6 (p=0.022), and hsCRP (p=0.002). In addition, patients who died presented higher mean levels of caspase 1 (p=0.043), IL-6 (p=0.03), and hsCRP (p=0.005). A higher percentage of patients with a 4+ pain score had worse but not significant 5-year Progression Free Survival (52.2% vs. 38.5%) and Overall Survival (39.1 vs. 20.5). We will also present preliminary data from the second ongoing pilot study evaluating whether inflammasome activation mediates the effects of MMJ on chronic pain.

Conclusions: Inflammasome activation and inflammation contribute to RT-related skin toxicity, pain, and worse overall survival. Therefore, inhibiting inflammasome activation with MMJ has the potential to improve breast cancer QOL and clinical outcomes.