TIP65 The Impact of Aromatase Inhibitor Use on Cardiorespiratory Fitness in Post-Menopausal Breast Cancer Patients

Background

Hormone receptor (HR)–positive breast cancer (BC) remains the most common malignancy among women in the United States. With improved treatments and survival, millions of BC survivors are living with the off-target effects of their treatments. Aromatase inhibitors (AIs) are an essential component in the treatment of HR-positive BC. Cytotoxic chemotherapies have demonstrated negative effects on cardiorespiratory fitness and skeletal muscle function and cause increased production of senescent T cells. These T cells have distinct surface markers allowing for their identification and are associated with worse cardiovascular outcomes, skeletal muscle damage, and reduction in cardiorespiratory fitness. The relationship between AIs and these variables is not yet well understood, despite data suggesting increased risk of cardiovascular disease associated with AIs. Our prospective trial is examining the association between AIs, cardiorespiratory fitness, skeletal muscle function, and immunosenescence in postmenopausal patients with BC.

Materials and Methods

This is a prospective, single-arm, observational study of postmenopausal women with stage 0 to III HR-positive, HER2 nonamplified BC who are to receive AI therapy. Patients are excluded if they had previous treatment with an AI, previous cardiotoxic chemotherapy, or are currently receiving antineoplastic agents. We plan to recruit 30 participants. Study measures are collected prior to and after 3 months of AI therapy.  Participants undergo baseline testing prior to starting AI therapy. This includes testing of maximum rate of oxygen consumption measured during exercise while on a stationary cycle ergometer, grip and quadriceps strength, body composition utilizing dual x-ray absorptiometry or bioelectrical impedance analysis, and 5 days of remote physical activity monitoring using accelerometers. Blood is drawn for mass cytometry and assessment of the inflammatory markers. Mass cytometry is utilized to measure concentrations of CD4+and CD8+CD28– CD57+T cells, which will allow for assessment of immunosenescence. Participants complete 3 written assessments to assess demographics, extent of physical activity (International Physical Activity Questionnaire [IPAQ]), and baseline symptoms (Breast Cancer Prevention Trial Symptom Scale [BESS]). The IPAQ and BESS help to identify level of physical activity and common musculoskeletal symptoms associated with AI use, respectively, as potential confounding variables. All of this testing is repeated after 3 months of AI therapy.

Statistical Methods

Paired-sample t tests will be used to determine the change in physiological and patient-reported outcomes from baseline to 3 months and used to generate effect sizes to inform future large-scale interventional trials. Relationships between changes in questionnaire metrics and physiological outcomes will also be assessed via Pearson correlations or Spearman correlations.

Status

This study is open at the University of Virginia and is currently enrolling.